Any prior anthracycline or platinum based therapy at any time
Must either have prior treatment with platinum-containing chemotherapy (Cohort 1) or be platinum-naïve and ineligible for treatment with cisplatin at time of enrollment (Cohort 2).
Patient must have developed disease progression during or following treatment with at least one platinum-containing regimen (e.g., gemcitabine/cisplatin [GC], methotrexate-vinblastine-doxorubicin-cisplatin [MVAC], carboplatin, gemcitabine [CarboGem]) for inoperable locally advanced or metastatic urothelial carcinoma or disease recurrence, or must be unfit or ineligible for cisplatin-based chemotherapy; there is no restriction on the number of prior lines of chemotherapeutics agents received\r\n* Patients who progressed within 12 months of treatment with a platinum-containing neoadjuvant or adjuvant regimen are considered second-line patients; therefore, these patients may be also eligible\r\n* Patients who are unfit or ineligible for cisplatin-based chemotherapy as defined by any one of the following criteria are eligible for this trial: \r\n** Eastern Cooperative Oncology Group (ECOG) performance score of 2\r\n** Creatinine clearance < 60 mL/min \r\n** A hearing loss (measured by audiometry) of 25 dB at two contiguous frequencies \r\n** Grade >= 2 peripheral neuropathy
Patients must have progressed during or after prior platinum-based chemotherapy; patients whose only prior platinum-based chemotherapy regimen was for stage I-III disease (i.e. patient has not received any platinum-based chemotherapy for stage IV or recurrent disease), disease progression on platinum-based chemotherapy must have occurred within one year from the last date that patient received that therapy; patients must have experienced disease progression during or after prior anti-PD-1 or anti-PD-L1 antibody monotherapy as their most recent line of treatment; prior PD-1/PD-L1 combination therapy is not permitted
Patients must either be eligible to be screened at progression on prior treatment or to be pre-screened prior to progression on current treatment; patients will either consent to the screening consent or the pre-screening consent, not both; these criteria are:\r\n* Screening at progression on prior treatment: to be eligible for screening at progression, patients must have received at least one line of systemic therapy for any stage of disease (stages I-IV) and must have progressed during or following their most recent line of therapy; for patients whose prior systemic therapy was for stage I-III disease only (i.e. patient has not received any treatment for stage IV or recurrent disease), the prior systemic therapy must have been a platinum-based chemotherapy regimen and disease progression on the platinum-based chemotherapy must have occurred within one year from the last date that patient received that therapy; for patients whose prior therapy was for stage IV or recurrent disease, the patient must have received at least one line of a platinum-based chemotherapy regimen or checkpoint inhibitor therapy (e.g. nivolumab or pembrolizumab)\r\n* Pre-screening prior to progression on current treatment: to be eligible for pre-screening, current treatment must be for stage IV or recurrent disease and patient must have received at least one dose of the current regimen; patients must have previously received or currently be receiving a platinum-based chemotherapy regimen or checkpoint inhibitor therapy (e.g. nivolumab or pembrolizumab); patients on first-line platinum-based treatment are eligible upon receiving cycle 1, day 1 infusion; Note: patients will not receive their sub-study assignment until they progress and the S1400 Notice of Progression is submitted
Recurrent, platinum resistant ovarian cancer (defined as progression within < 6 months from completion of platinum based therapy; the date should be calculated from the last administered dose of platinum therapy)
Patients with prior treatment with bevacizumab (or any other anti vascular therapy, e.g., cediranib) for platinum resistant recurrence; (Note: prior bevacizumab in initial therapy and/or platinum sensitive recurrent setting is allowed)
Patients must have received first-line/induction systemic therapy comprising of immunotherapy and/or platinum-based chemotherapy (a total of 4 cycles or courses), and achieved stable disease or a partial response.
Patients who never received platinum-containing regimen for Small-cell Lung Cancer (SCLC)
The small cell lung cancer must have progressed radiographically following a platinum-based (cisplatin and/or carboplatin) standard prior chemotherapy regimen; any number of interval prior lines of therapy is allowed; patients who have received prior platinum-based chemotherapy and radiation for limited stage SCLC and have subsequently developed relapsed disease are eligible, as long as the platinum-based therapy was given within 12 months prior to the time of relapse
Prior lines of therapy must include a platinum-based therapy. Investigational agents used in combination with standard therapies are allowed. Participants who received platinum-based neoadjuvant or adjuvant therapy and subsequently received platinum-based therapy as first-line therapy are eligible.
Participants who have completed neo-adjuvant or adjuvant therapy with a platinum doublet and have experienced disease recurrence within 6 months of completing the platinum doublet are eligible.
Maintenance or switch maintenance therapy after first-line chemotherapy will be considered part of the first-line regimen and is acceptable. Participants who completed and progressed on a platinum-containing regimen as adjuvant, neoadjuvant, or part of a course of chemoradiation therapy given from locally advanced disease and developed recurrent (local or metastatic) disease within the 6 months before screening would be counted as having received 1 prior platinum-containing regimen and therefore would not require re-treatment with a platinum-containing regimen for Stage IIIB, IV, or recurrent disease and are eligible. However, participants must have received at least 2 cycles of a platinum doublet based chemotherapy before discontinuation for toxicity. If participants received only one cycle of a platinum doublet and discontinue due to clear progression, that regimen should be counted as a prior line of therapy.
Part C: Participants with advanced (locally advanced incurable or metastatic) histologically or cytologically confirmed high-grade serous ovarian cancer (high nuclear Grades 2 or 3). Participants should have either platinum-refractory (disease progression during initial platinum therapy) or platinum-resistant (disease progression <6 months after completion of platinum therapy) disease.
Subjects with NPC must have received, or been intolerant to, a platinum-based combination as part of their prior therapy for advanced/metastatic disease;
Patients with esophageal cancer must have received, or been intolerant to, a platinum-based combination as part of their prior therapy for advanced/metastatic disease;
Patients with gastric cancer must have received, or been intolerant to, a fluoropyrimidine-platinum combination as part of their prior therapy for advanced/metastatic disease; Subjects in Part B must not have had more than 3 prior lines of cytotoxic chemotherapy;
Have not tolerated or have progressed or relapsed on or within 6 months of platinum-based chemotherapy
Has received more than 2 platinum-based regimens against SCLC
Histologically or cytologically confirmed Small Cell Lung Cancer (SCLC): Part A: RR SCLC who progressed or recurred following platinum-based chemotherapy; Note: Subjects with a diagnosis of combined small cell carcinoma with >50% small cells may be considered for inclusion in the dose escalation phase of part A based on investigator discretion and after discussion with the medical monitor Part B: ED SCLC with ongoing clinical benefit (stable disease [SD], partial response [PR], or complete response [CR]) following no more than 6 cycles of first-line platinum-based chemotherapy with the last dose of chemotherapy greater then equal to 28 days prior to the study day 1 (first-line consolidation setting)
Cohort A Dose Escalation (Ribociclib + PDR001): Ovarian participants:\r\n* Metastatic epithelial ovarian cancer, fallopian tube or peritoneal cancer; all histologies (including serous, mucinous, endometrioid, clear cell, malignant mixed Mullerian tumor [MMMT]s and mixed histologies) and tumor grades are eligible\r\n* Prior Chemotherapy: Participants may have received any number of prior lines of chemotherapy for metastatic disease, as long as the last dose is >= 21 days prior to first dose of study treatment\r\n** Must have received a first-line platinum-based therapy and have disease that is platinum-resistant\r\n*** Platinum-resistant disease is defined as disease relapse within 2 to 6 months of prior platinum-based chemotherapy
Cohort A Dose Expansion (Ribociclib + PDR001): Prior chemotherapy: \r\n* Participants may have received any number of prior lines of chemotherapy for metastatic disease, as long as the last dose is >= 21 days prior to first dose of study treatment\r\n** Must have received a first-line platinum-based therapy and have disease that is platinum-resistant \r\n*** Platinum-resistant disease is defined as disease relapse within 2 to 6 months of prior platinum-based chemotherapy\r\n** Must have received a first-line platinum-based chemotherapy regimen and have relapsed despite standard therapy
Ovarian cancer patients must be resistant to platinum therapy (i.e. within 6 months of last platinum therapy)
Patients who have not previously been treated with platinum-based based doublet chemotherapy and who, in the judgment of the investigator, have rapidly progressive disease such that serious complications may arise from disease progression within the next 12 weeks will be excluded
Second-line patients who have disease progression during or following platinum-containing chemotherapy.
Have progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.
platinum (cisplatin or oxaliplatin),
Platinum resistant Grade 2 or 3 ovarian, primary peritoneal or fallopian tube cancer
Patients must have recurrent platinum-resistant disease, defined as progression < 6 months after completion of platinum-based chemotherapy or as persistent disease that remains after completing the most recent line of platinum-based therapy; the platinum-free interval should be calculated from the last administered dose of platinum therapy
Prior therapy allowed:\r\n* At least one and no more than 3 platinum based chemotherapy regimens\r\n* Up to 2 non-platinum, cytotoxic regimen\r\n* There is no limit on use of prior biological therapies (hormonal or targeted therapy)\r\n* NOTE: Prior immunotherapy is not allowed
Stage IIIB or IV patients must have progressed after first line platinum based chemotherapy; patients with stage I-IIIB NSCLC who have progressed within 6 months of a full dose platinum based regimen as adjuvant therapy or with radiotherapy are eligible; patients who received weekly low dose chemotherapy with radiation only are not eligible
Patients with primary mediastinal non seminomatous germ cell tumor are eligible if they have received first line platinum based chemotherapy and their recurrence is not amenable to surgical resection based on the treating physician’s expert opinion
Patients with late relapse (> 2 years) of non seminomatous germ cell tumors are eligible if they have received first line platinum based chemotherapy and their recurrence is not amenable to surgical resection based on the treating physician’s expert opinion
In Part B, the patients recruited to one of the eight expansion arms must have advanced solid tumors of the following types: Arm 1: Patients with relapsed, platinum-sensitive high grade epithelial, non-mucinous, ovarian cancer, fallopian tube, or primary peritoneal cancer must meet the following criteria: i. Patients must have at least 2 prior platinum-containing treatments in any treatment setting. • Note: patients could have received additional therapy after the last platinum-containing regimen if the other eligibility criteria are met. ii. Patients must have platinum-sensitive recurrent disease and must not have progressed (by RECIST v1.1 criteria) within 6 months of the completion of the last platinum containing regimen. • Note: patients can receive additional non-platinum based chemotherapy for recurrence after the last platinum containing regimen if the criteria for platinum sensitivity are met. iii. Arm 1a: Patients with relapsed, platinum-sensitive high grade epithelial, non-mucinous, ovarian cancer, fallopian tube, or primary peritoneal cancer (EOC) with either known deleterious or suspected deleterious germline or somatic BRCA1/2 mutations or with DNA HRD • If HRD or BRCA1/2 mutation status is unknown or has not been previously evaluated, then the patient must undergo tissue screening using the Myriad myChoice® diagnostic test to determine eligibility. iv. Arm 1b: Patients with relapsed, platinum-sensitive high grade epithelial, non-mucinous, ovarian cancer, fallopian tube, or primary peritoneal cancer (EOC) without either known deleterious or suspected deleterious germline or somatic BRCA1/2 mutations or without DNA HRD • If HRD or BRCA1/2 mutation status is unknown or has not been previously evaluated, then the patient must undergo tissue screening using the Myriad myChoice® diagnostic test to determine eligibility. Arm 2: Patients with triple negative breast cancer must meet the following criteria: i. Patients with either known deleterious or suspected deleterious germline or somatic BRCA1/2 mutations or with DNA HRD. • If HRD or BRCA1/2 mutation status is unknown or has not been previously evaluated, then the patient must undergo tissue screening using the Myriad myChoice® diagnostic test to determine eligibility. ii. Patients with 0-1 prior platinum-containing treatment in any treatment setting. • Note: patients could have received additional therapy after the last platinum-containing regimen if the other eligibility criteria are met. iii. Patients who have received ? 3 prior lines of therapy in the advanced or metastatic setting. Arm 3: Patients with metastatic castration-resistant prostate cancer, including but not limited to mutations in HR pathways and/or defined by HRD algorithms, and must meet the following criteria: i. Patients with either known deleterious or suspected deleterious germline or somatic BRCA1/2 mutations or with DNA HRD. • If HRD or BRCA1/2 mutation status is unknown or has not been previously evaluated, then the patient must undergo tissue screening using the Myriad myChoice® diagnostic test to determine eligibility. ii. The patient may be either chemotherapy-naïve, but must have received prior abiraterone acetate and/or enzalutamide treatment, or have previously had no more than two taxane-based chemotherapy regimens including docetaxel and carbazitaxel. If docetaxel is used more than once, this will be considered as one regimen. iii. At least 2 weeks since the completion of prior flutamide, bicalutamide, and nilutimide, or enzalutamide and abiraterone treatment. iv. At least 2 weeks from any radiotherapy, with the exception of a single fraction of radiotherapy for the purposes of palliation (confined to one field). v. Documented prostate cancer progression with one of the following:
Platinum-resistant/refractory disease, defined as progressive disease at the first tumor assessment while receiving platinum-based chemotherapy or within 6 months after treatment (for patients in Part B; disease-specific expansion arms only).
NSCLC - Prior treatment regimens must include a platinum-based therapy
Concomitant EGFR TKI and platinum based chemotherapy as first line regimen.
Platinum-based chemotherapy as first line treatment
Willing to agree to periodic contact with a member of the study team during the period that the cancer has not recurred and/or has not become platinum resistant
Platinum resistant or refractory ovarian, primary peritoneal or fallopian tube cancer of any subtype; Note: platinum-sensitive disease is allowed in cases where there is a contraindication to platinum-based therapy (i.e., allergy to platinum); this must be reviewed and approved by the principal investigator
Prior treatment with Doxil, topotecan, Gemzar or Taxol chemotherapy for platinum-resistant cancer; Note: Allowed prior therapy with Doxil or Gemzar if given for platinum sensitive disease in combination with a platinum drug AND the Avatar data indicates a drug other than Doxil or Gemzar would be effective; Note: Allowed prior therapies for patients following confirmation of platinum-resistant cancer include:\r\n* Therapeutic antibodies, such as bevacizumab\r\n* Small molecule kinase inhibitors, such as pazopanib\r\n* Vaccines and immunotherapy\r\n* Poly (ADP-ribose) polymerase (PARP) inhibitors\r\n* Endocrine therapies, such as letrozole\r\n* Metronomic oral cytoxan\r\nAll of these exceptions should be confirmed with the principal investigator (PI) prior to registration
Patients who are platinum-sensitive or platinum resistant
Patients must have recurrent or persistent, platinum resistant or refractory epithelial ovarian, fallopian tube or primary peritoneal carcinoma; platinum-resistant disease is defined as a recurrence within 6 months of completing, platinum-based chemotherapy
Patients must have had one prior taxane and platinum-based chemotherapeutic regimen for management of primary disease containing carboplatin, cisplatin, or another organoplatinum compound; this initial treatment may have included intraperitoneal therapy, consolidation, non-cytotoxic (biologic/targeted agents) or extended therapy administered after surgical or non-surgical assessment; there is no maximum number of prior regimens; Note: use of bevacizumab as maintenance therapy after initial adjuvant platinum-based chemotherapy is allowed so long as platinum-resistant recurrence occurred subsequent to a separate platinum-based regimen AND more than 6 months after completion of bevacizumab maintenance
Prior therapy\r\n* Patients must have had one prior platinum-based chemotherapeutic regimen for management of primary disease containing carboplatin, cisplatin, or another organoplatinum compound; this initial treatment may have included intraperitoneal therapy, high-dose therapy, consolidation, non-cytotoxic agents or extended therapy administered after surgical or non-surgical assessment\r\n* Patients are allowed to receive, but are not required to receive, two additional cytotoxic regimens (a total of 3 cytotoxic regimens) for management of recurrent or persistent disease according to the following definition:\r\n** Patients who have received only one prior cytotoxic regimen (platinum-based regimen for management of primary disease), must have a platinum-free interval of less than 12 months, or have progressed during platinum-based therapy, or have persistent disease after a platinum-based therapy\r\n** Patients must NOT have received any non-cytotoxic therapy for management of recurrent or persistent disease other than bevacizumab containing regimens; patients are allowed to receive, but are not required to receive, biologic (non-cytotoxic) therapy as part of their primary treatment regimen
Cohort 4: Have primary platinum refractory disease.
Epithelial Ovarian Cancer: histologically confirmed diagnosis (by either primary surgical specimen or biopsy for recurrence) of recurrent platinum-resistant/refractory EOC (i.e., disease recurrence within 6 months of completion of or progression during platinum-based chemotherapy). Note that patients with germ cell, sex cord stroma, carcinosarcoma, or sarcoma are eligible only if the tumor has a mixed endometrioid component with a documented Wnt signaling alteration.
Platinum-resistant ovarian cancer is defined as disease that responded to primary platinum therapy and then progressed within 6 months or disease that progressed during or within six months of completing a subsequent platinum therapy.
Primary platinum refractory disease is defined as disease that has not responded to a platinum-based regimen or experienced disease recurrence within 3 months of completing a first-line platinum-based regimen.
PHASE II INCLUSION CRITERIA: Patients must have cytologically or histologically confirmed ES-SCLC and must not have progressed after first line platinum-based chemotherapy regimen before randomization
Platinum resistance, defined as disease progression within 6 months of completing a platinum-containing chemotherapy regimen. For NSCLC
Inclusion Criteria: All subjects\n\n          1. Age ?18 years old.\n\n          2. Confirmed malignancy at advanced or metastatic stage.\n\n          3. ECOG status ? 1.\n\n          4. Adequate bone marrow function.\n\n          5. Adequate renal and hepatic function.\n\n          6. Females of childbearing potential and non-sterile males must agree to use highly\n             effective methods of birth control throughout the course of study and at least up to\n             90 days after last dosing.\n\n          7. Must have measurable or evaluable disease per RECIST [Dose escalation phase only]\n\n             Additional inclusion criteria 8 - 12 are specific to tumor types in dose expansion\n             phase:\n\n          8. Ovarian cancer\n\n               1. Previously received at least 1 line of platinum containing chemotherapy.\n\n               2. No progression or recurrent disease in 6 months from last platinum containing\n                  regimen.\n\n          9. Triple-Negative Breast Cancer\n\n             a. 0 - 1 prior platinum-containing regimen (any treatment setting) and received ? 3\n             prior regimens (advanced or metastatic setting).\n\n         10. Prostate cancer\n\n               1. Documented progressive disease.\n\n               2. Chemotherapy-naïve or previously received ?2 taxane-based regimens.\n\n               3. May be pre-or post-treatment with a novel androgen receptor targeted agent.\n\n               4. Completed in ? 2 weeks radiation or treatment with anti-androgen agents.\n\n         11. Ovarian, breast and prostate cancer: If homologous recombinant deficiency (HRD) or\n             BRCA status unknown, need pre-screening for eligibility.\n\n         12. Small cell lung and gastric cancer: previously received ? 2 prior lines of therapy.\n\n        Exclusion Criteria: All subjects\n\n          1. Prior exposure to a PARP inhibitor.\n\n          2. Prior chemotherapy, biologic therapy, immunotherapy or investigational agents within 3\n             weeks prior to start of study treatment.\n\n          3. Refractory to platinum-based therapy.\n\n          4. Toxicity of ? Grade 2 from prior therapy.\n\n          5. Major surgery or significant injury ? 4 weeks prior to start of study treatment.\n\n          6. History of other active malignancies within 2 years with exception of (i) adequately\n             treated in situ carcinoma of the cervix, (ii) non-melanoma skin cancer, or (iii)\n             localized adequately treated cancer with curative intent or malignancy diagnosed > 2\n             years ago with no evidence of disease and no treatment ? 2 years prior to study\n             treatment.\n\n          7. Untreated leptomeningeal or brain metastasis.\n\n          8. Active infection requiring systemic treatment.\n\n          9. Known human immunodeficiency virus (HIV) or active viral hepatitis.\n\n         10. Active, clinically significant cardiac disease or any Class 3 or 4 cardiac disease,\n             ventricular arrhythmia or CVA ? 6 months prior to start of treatment.\n\n         11. Active, clinically significant gastrointestinal disease.\n\n         12. Use of any medications or food known to be strong or moderate cytochrome P450, family\n             3, subfamily A (CYP3A) inhibitors or strong inducers.\n\n         13. Pregnant or nursing females.
Received any chemotherapy (including irinotecan) other than platinum and fluoropyrimidine with or without anthracycline or taxane for advanced gastric or GEJ adenocarcinoma
Part 2, Cohort 2, Must have received ? 1 prior treatment regimen for ovarian cancer, at least 1 of which is a platinum-based regimen
Part 2,Cohort 3, Must have received only 1 prior platinum-based regimen. Patient must have primary platinum refractory OC (defined as progression either while on initial treatment with the platinum-based therapy or within 1 month following the last dose of treatment)
Prior systemic chemotherapy, except if given as part of a multimodal treatment for locally advanced disease which was completed more than 3 months before Day 1 or more than 6 months prior to Day 1 if platinum-based
Prior platinum-based chemotherapy
Disease progression after treatment with at least one line of chemotherapy that included a platinum agent in combination with pemetrexed
Participants who have received prior platinum chemotherapy
Phase Ib: Subjects who progressed after first-line platinum-based chemotherapy and who are candidates for second-line therapy.
Patients must have histologically confirmed high grade serous ovarian or primary peritoneal or fallopian tube cancer; platinum resistant disease is defined as progression within 6 months after last platinum regimen
Patients with primary platinum refractory disease, defined as progression while first line platinum based chemotherapy
Prior treatment with any PARP inhibitor, mitoxantrone, cyclophosphamide or any platinum-based chemotherapy
Cohort C: Eligible patients must have received no more than 4 lines of systemic cytotoxic chemotherapy and must have disease resistant to platinum therapy (disease that progressed during or within six months of completing subsequent platinum therapy); primary platinum refractory patients are eligible providing they meet other eligibility criteria; in addition to platinum agents, patients must have received and failed, or have been intolerant to taxanes, liposomal doxorubicin or other agents known to confer clinical benefit; patients are not required to fail all these agents if, in the investigator’s opinion, patients would benefit from treatment on current protocol
Diagnosis of radiological progression while on or after first platinum-based systemic therapy
Radiologic evidence for progressive disease after >= 1 prior platinum containing chemotherapy regimen in the perioperative or metastatic setting
Must have received prior platinum containing chemotherapy for advanced/metastatic non-small cell lung cancer, or have refused or be ineligible for such therapy; prior neoadjuvant/adjuvant platinum containing chemotherapy will count has having received prior platinum, provided that disease recurred within 6 months of completion of neoadjuvant/adjuvant therapy
Dose expansion:\r\n* HPV-associated locally advanced or metastatic platinum-resistant solid tumor malignancy; HPV positivity defined by positive p16 immunohistochemistry, polymerase chain reaction, or in-situ hybridization assessment of archival tissue (primary or metastatic) in a Clinical Laboratory Improvement Act (CLIA)-certified laboratory; availability of pathology report from CLIA-certified lab demonstrating positive HPV status by p16 IHC, polymerase chain reaction, or in situ hybridization qualifies for eligibility determination; analysis of fresh tumor tissue is permitted in cases where archival tissue is not available\r\n* Platinum resistance defined as prior progression (radiographic or clinical) either during or within 6 months following completion of platinum-based chemotherapy\r\n* Platinum-based therapy as most recent systemic therapy prior to enrollment allowed but not required
Epithelial ovarian carcinoma (including primary peritoneal disease and/or fallopian tube carcinomas and/or endometrial adenocarcinomas) regardless of platinum sensitivity.
Resistant/Refractory Small Cell Carcinoma (SCC) patients in 3rd line or beyond that have previously received platinum or patients in 2nd line with platinum-refractory or platinum-resistant disease
Epithelial Ovarian Cancer (EOC), fallopian tube or primary peritoneal cancer and Malignant Mixed Mullerian Tumor (MMMT) of the ovary or uterus. Excludes other non-epithelial ovarian tumors and ovarian tumors with low malignant potential. Patients must have previously received a platinum based regimen for advanced/metastatic disease or have platinum resistant or refractory disease defined as relapse within 6 months. EOC - specific criteria: Patients who progress or have stable disease during first-line treatment or who relapse within 1 month are considered to be 'platinum-refractory'. Patients who respond to primary treatment and relapse within 6 months are considered 'platinum-resistant', and patients who relapse more than 6 months after completion of initial therapy are characterized as 'platinum-sensitive'. Patients who relapse 6-12 months following the end of their initial regimen are classified as 'partially sensitive'. Platinum sensitive patients may be enrolled but must have failed or declined all other lines of FDA approved therapy
A washout period of 6-weeks for patients treated last with platinum based chemotherapy. A 2-week washout period for patients treated with all other therapies.
Patients must have previously received a platinum based regimen for advanced/metastatic disease and progressed or have platinum resistant or refractory disease defined as relapse within 6 months.
Participants must have adequate organ and marrow function as defined below both prior to administration of RRx-001 and prior to administration of platinum doublet based regimen:
History of needing to permanently discontinue prior platinum doublet-based regimen for toxicity (e.g., cisplatin causing renal impairment, ototoxicity, or severe neuropathy).
Known severe hypersensitivity to the platinum agent (i.e., carboplatin or cisplatin) or prior partner of platinum agent (i.e., etoposide for SCC and HGNEC; nab-paclitaxel, paclitaxel, or pemetrexed for NSCLC; paclitaxel, pegylated liposomal doxorubicin, docetaxel or gemcitabine for ovarian) planned for the platinum therapy period. If the patient has had prior hypersensitivity reaction to the drug partner of platinum, a patient may enroll as long as it is acceptable to treat with platinum and one of the alternative chemotherapy partner agents.
Platinum-resistant or platinum-refractory disease, defined as either 1) less than a complete response to the most recent carboplatin- or cisplatin-containing chemotherapy regimen, 2) serum cancer antigen (CA)-125 >= 2 x upper limit of normal (ULN) within 180 days of last dose of carboplatin- or cisplatin-containing chemotherapy, confirmed by a second CA-125 (the second CA-125 does not have to be within 180 days of chemotherapy), or 3) CT or positron emission tomography (PET)/CT evidence of cancer recurrence within 180 days of last dose of carboplatin- or cisplatin-containing chemotherapy
Patients enrolling in cohort 5, the recurrent platinum-resistant sporadic high grade serous epithelial or high grade endometrioid ovarian cancer group, must have a negative family history of HBOC syndrome, or negative gBRCA1/2m test; patients should have recurrent platinum-resistant - defined as disease recurrence by imaging within 6 months of the last receipt of platinum-based chemotherapy; rising CA125 only is not considered as platinum-resistant disease; patients with primary platinum refractory disease defined as progression during or within 3 months after receiving first-line platinum based chemotherapy are not eligible
Patients enrolling in cohort 6, the recurrent platinum-resistant sporadic high grade serous epithelial or high grade endometrioid ovarian cancer group, must have a negative family history of HBOC syndrome, or negative gBRCA1/2m test; patients should have recurrent platinum-resistant, defined as disease recurrence by imaging within 6 months of the last receipt of platinum-based chemotherapy; this cohort should have measurable (defined by RECIST v1.1) but without biopsiable disease, determined by principle investigator (PI) and interventional radiology (e.g., cystic abnormal mass, not safely biopsiable disease); rising CA125 only is not considered as platinum-resistant disease; patients with primary platinum refractory disease defined as progression during or within 3 months after receiving first-line platinum based chemotherapy are not eligible
All patients must have received a prior platinum-based chemotherapy regimen for treatment of urothelial cancer and must now be considered refractory to platinum-based chemotherapy; patients may have received the platinum-containing regimen either in the peri-operative or metastatic setting; patients may have received any number of additional prior therapies, and may have received prior immune therapies
Patients must have platinum resistant (platinum-free interval < 6 months) or platinum refractory disease as per Gynecological Cancer Intergroup (GCIC) criteria
Prior use of weekly paclitaxel or bevacizumab in the platinum resistant (disease progression within 6 months of platinum based chemotherapy)/refractory (disease progression during or following the 3 months of the first line platinum based chemotherapy) setting
Subjects with both platinum-sensitive and platinum-refractory disease will be eligible
Patients with recurrent endometrial, ovarian, fallopian tube or primary peritoneal cancer must have received at least one platinum-based chemotherapy regimen
For the dose expansion cohort patients with first-recurrence platinum-sensitive ovarian cancer must be excluded
Primary platinum refractory disease (disease progression on first platinum treatment or recurrence within 3 months of completing first platinum regimen)
Patients must have received prior platinum and pemetrexed based therapies. Response to platinum is not an eligibility criterion for enrollment
Have experienced progressive disease after at least one previous regimen of platinum-based chemotherapy
Platinum-sensitive disease (exceptions allowed: patient has had a hypersensitivity reaction to platinum or the treating oncologist thinks that further platinum therapy is not in the patient’s best interest)
Ovarian cancer cohort only: Subjects must have platinum refractory or resistant disease.
Patients must be platinum-resistant or platinum-ineligible by fulfilling at least one of the criteria defined below:\r\n* Disease persistence or recurrence within 6 months of completing definitive radiotherapy for locally advanced disease, where platinum chemotherapy was administered as a component of induction and/or concurrent systemic treatment\r\n* Disease progression during, or within 6 months, of treatment with platinum chemotherapy (eg. carboplatin or cisplatin) in the recurrent/metastatic setting\r\n* The patient is not an acceptable candidate for platinum chemotherapy due to medical comorbidities, in the judgment of the local investigator\r\n* Prior platinum exposure may have occurred in any line of therapy (first line, second line, etc.) and is not required to be the most recent therapy received
Must have received and have progressed, or are intolerant to at least one systemic regimen (platinum- or fluoropyrimidine-based chemotherapy regimen for metastatic or recurrent disease or progressed within 6 month of completion of adjuvant therapy with a platinum- or fluoropyrimidine-based regimen)
Histologically confirmed Small Cell Lung Cancer (SCLC) with radiographically documented disease progression or recurrence after at least one platinum-based regimen:
Prior platinum-based chemotherapy for the treatment of prostate cancer
Evidence of progressive disease (PD) on or within 6 months of a platinum (cisplatin or carboplatin) regimen: at least 1 prior regimen must have contained a platinum-taxane combination
Patients with platinum sensitive ovarian cancer must have progressed within 6 months of their last platinum-containing regimen, consistent with definition of platinum resistant disease
Patients with platinum resistant ovarian cancer must have progressed through at least one prior chemotherapy regimen for recurrent ovarian cancer
Patients who did not achieve PR or CR as per the Lugano criteria following at least 1 cycle of platinum?based salvage chemotherapy, or patients not eligible for platinum based therapy or beam induction therapy due to decreased ejection fraction (< 40%)
Patients must have had one prior platinum-based chemotherapeutic regimen for management of primary disease containing carboplatin, cisplatin, or another organoplatinum compound; this initial treatment may have included intraperitoneal therapy, high-dose therapy, consolidation, noncytotoxic agents or extended therapy administered after surgical or non-surgical assessment
Patients must be considered platinum resistant according to standard GOG criteria, which defines patients as having had a treatment-free interval following platinum of less than 6 months
Platinum-refractory ovarian, fallopian tube, or primary peritoneal carcinoma
Patients must have recurrent, platinum-resistant disease (defined as having relapsed within 6 months of last platinum-containing regimen) or be unable to receive further platinum therapy; there is no limit on the number of prior treatment regimens; however, patients may not have previously received weekly paclitaxel in the recurrent setting; previous dose dense paclitaxel as initial therapy is allowable
Recurrent epithelial ovarian cancer, fallopian tube, or primary peritoneal cancer meeting one of the following minimal prior treatment requirement (no limit to the maximum number of prior treatments):\r\n* Platinum resistant: may receive FATE-NK100 as 2nd line (as 1st salvage therapy) with platinum resistant is defined as disease that has responded to initial chemotherapy but demonstrates recurrence within a relatively short period of time (< 6 months) following the completion of treatment\r\n* Platinum sensitive: may receive FATE-NK100 as 3rd line therapy (as 2nd salvage therapy) with platinum sensitive is defined as the recurrence of active disease in a patient who has achieved a documented response to initial platinum-based treatment and has been off therapy for an extended period of time (>= 6 months)
Prior disease progression while receiving platinum chemotherapy; or any platinum chemotherapy within the last 6 months\r\n* For all patients (except breast cancer patients) who received platinum-based adjuvant or neo-adjuvant chemotherapy, at least 6 months must have passed between the last dose of platinum-based therapy and the development of metastatic disease\r\n* For breast cancer patients, at least 12 months must have passed between the last dose of platinum-based adjuvant or neo-adjuvant therapy and the development of metastatic disease
Prior progression on only 1 line of chemotherapy in the advanced/metastatic setting containing a fluoropyrimidine and/or platinum compound
Progression after treatment with least one platinum containing chemotherapy regimen
Patients must have progressed during or after first-line treatment for metastatic or unresectable disease with either a platinum-based regimen (e.g. carboplatin + etoposide, ifosfamide, and cisplatin [VP16], cisplatin + VP-16, leucovorin calcium, fluorouracil, and oxaliplatin [FOLFOX]) OR temozolomide-based regimen; patients must have failed at least one line of therapy but no maximum number of therapies is exclusionary (i.e. second-line therapy and beyond)
Histologically confirmed metastatic non-small cell lung cancer (NSCLC) with disease recurrence or progression during or after prior platinum-containing doublet chemotherapy regimen
Patients with recurrent disease > 6 months after adjuvant or neoadjuvant platinum- based chemotherapy, who also subsequently progressed during or after a platinum- doublet regimen given to treat the recurrence, are not excluded.
STUDY TREATMENT: Platinum-based chemotherapy prior to chemoradiation is permitted but not mandatory
Any number of prior treatments is allowed; must have failed at least one treatment regimen for metastatic disease and must have failed platinum-based chemotherapy (including as treatment for localized disease) or be deemed ineligible for platinum-based therapy by the treating medical oncologist
Prior treatment with a PARP inhibitor, cyclophosphamide, or mitoxantrone chemotherapy. Patients who discontinued prior platinum based chemotherapy <=6 months prior to screening or whose disease previously progressed on platinum based therapy at any time in the past are also excluded.
Time from the last line of platinum-based chemotherapy of less than 6 months.
Disease that progressed while receiving initial line of platinum-based chemotherapy.
Disease progression following frontline platinum doublet therapy given for metastatic or recurrent disease; there is no restriction on prior lines of therapy following receipt of initial platinum doublet therapy\r\n* Continuation maintenance therapy following platinum-based chemotherapy will not be considered as a separate line of therapy\r\n* Prior platinum-containing adjuvant, neoadjuvant, or definitive chemoradiation therapy given for locally advanced disease is considered first-line platinum therapy only if recurrent disease developed within 6 months of completing therapy\r\n* Patients with activating EGFR mutations must have received an EGFR tyrosine kinase inhibitor directed therapy prior to platinum therapy\r\n* Patients with ALK translocations must have received an ALK tyrosine kinase inhibitor directed therapy prior to platinum therapy
Subjects must have extensive-stage disease (by National Comprehensive Cancer Network [NCCN] criteria) that has been previously treated with first line platinum-based chemotherapy; patients must either have persistent or progressive disease after platinum based therapy
Platinum-refractory disease, or ineligible/unfit for platinum-based therapy
Platinum-resistant recurrent or metastatic epithelial ovarian carcinoma
Disease has progressed or recurred during or less than 6 months after platinum-based chemotherapy at some point during the subject's course.
Patients must have had at least one prior line of platinum-based chemotherapy or patient must have refused cytotoxic chemotherapy; progressive disease must be documented prior to study entry and patients must have advanced, unresectable disease that is not amenable to surgical resection
Women with platinum-sensitive recurrent ovarian, fallopian or primary peritoneal cancer (defined as recurrent disease > 6 months after completing last platinum-based chemotherapy) eligible to receive platinum-based doublet chemotherapy
Must have had at least 1 prior line of platinum-based therapy
Platinum-resistant disease (as defined as progressive disease within 6 months of completion of chemotherapy with a platinum agent)
One of the following:\r\n* Locally advanced or metastatic non-small cell lung cancer that has progressed after at least 1 line of platinum based chemotherapy\r\n** Patients may have received up to 2 prior lines of chemotherapy\r\n** Patients with actionable alterations in EGFR/ALK/ROS1/BRAF must also have progressed after treatment with a tyrosine kinase inhibitor appropriate for their genetic alteration\r\n** Untreated patients who refuse 1st line platinum based chemotherapy are also eligible\r\n* Squamous cell carcinoma of the head and neck whose disease has progressed after at least 1 line of platinum based chemotherapy\r\n** Patients may have received up to 2 prior lines of chemotherapy\r\n** Untreated patients who refuse 1st line platinum based chemotherapy are also eligible\r\n** Patients who relapse within 6 months of adjuvant cisplatin based concurrent chemoradiation, or neoadjuvant cisplatin based therapy can be considered eligible without an additional course of platinum chemotherapy for relapsed disease\r\n** Patients may have either locally recurrent or distant metastatic disease
Have a diagnosis of ovarian, fallopian tube, or primary peritoneal cancer patients who had a complete response to primary treatment with platinum based chemotherapy, have progressed within 6 months of completing platinum based chemotherapy and have subsequently received at least one, non-platinum-based, therapy
Platinum resistant or refractory disease as defined by progression of disease on a platinum-containing regimen or recurrence of disease within 180 days of previous platinum treatment.
Either ineligible for first-line cisplatin-based chemotherapy or have disease progression during or following treatment with at least one platinum-containing regimen.
Patient has received prior treatment with AM0010 or fluoropyrimidine/platinum containing regimen
Ongoing response of stable disease or better following 4 cycles of platinum-based first line chemotherapy
Must have received at least one line of standard systemic treatment for locally advanced or metastatic disease setting of the respective tumor type; for NSCLC, it is either PD-1/PD-L1 inhibitor, or platinum-containing chemotherapy, or an EGFR tyrosine kinase inhibitor or an ALK inhibitor if sensitizing mutation present; TNBC: platinum-containing chemotherapy; PDAC: fluorouracil (5-FU-), gemcitabine-, or taxane-containing chemotherapy either with or without radiation therapy; SCLC: platinum-containing chemotherapy for limited or extensive stage disease
Patients with recurrent or refractory epithelial ovarian, primary peritoneal or fallopian tube carcinoma, who have received platinum containing chemotherapy and either has platinum refractory or resistant disease, or if platinum sensitive disease, have received >= 2 lines of chemotherapy; subjects may have received PARP inhibitors, bevacizumab, or immunotherapy
For subjects in Group A with neuroendocrine prostate cancer (NEPC), previous use of at least one platinum-containing chemotherapy regimen
Patient must have prior treatment with a platinum plus pemetrexed regimen
Patients must have platinum-sensitive or platinum-resistant recurrent or persistent or refractory ovarian, fallopian tube, or primary peritoneal carcinoma AND have one or more of the following characteristics documented on a validated platform (documented genetic test report is required); historic report is permitted\r\n* A germline BRCA1 or BRCA2 deleterious alteration\r\n* A somatic mutation in BRCA1 or BRCA2 detected in a tumor sample or on circulating tumor deoxyribonucleic acid (DNA)\r\n* Carry a known or likely loss of function alteration in one or more of homologous recombination or mismatch repair pathway genes\r\n* Demonstrate a genomic phenotype of homologous recombination (HR) deficiency as measured by a loss-of-heterozygosity (LOH)-high score\r\n** Recurrent ovarian cancer is defined as recurrence of disease in a patient who achieved initial complete response to primary therapy\r\n** Persistent ovarian cancer is defined as having residual disease in the form of elevated tumor markers or microscopic or clinically evident disease in a patient who has completed and apparently responded to initial chemotherapy\r\n** Refractory ovarian cancer is defined as patients who have failed to achieve at least a partial response to therapy including patients with either stable disease or disease progression during primary therapy\r\n** Platinum-sensitive is defined as achievement of documented response to initial platinum-based treatment and has been off treatment for an extended period of time (more than 6 months)\r\n** Platinum-resistant is defined as relapse within 6 months of last platinum-based chemotherapy or progression while on platinum-based therapy
Patients must have histologically or cytologically confirmed advanced metastatic or unresectable epithelial ovarian cancer, primary peritoneal cancer or fallopian tube cancer that is relapsed and resistant (recurred less than 6 months after chemotherapy) or refractory (progressed on chemotherapy) to prior platinum- and taxane-based standard care systemic regimen; or patients who are not eligible for additional platinum therapy; histopathologic diagnosis must be confirmed in the laboratory of pathology (LP), National Cancer Institute (NCI)
Prior platinum-based chemotherapy for the treatment of prostate cancer
Up to three previous lines of therapy, of which one must have been a platinum-based doublet therapy and no more than two were cytotoxic chemotherapy
Relapse following platinum-based chemotherapy or documented progressive disease while on platinum-based chemotherapy
Participant can be either platinum-sensitive (platinum free interval [PFI] >= 6 months prior to recent recurrence) or platinum-resistant (PFI < 6 months prior to recent recurrence); if the participant has a platinum sensitive disease, she may only enroll in this clinical trial if there is a contraindication for her to receive further treatment with platinum-based chemotherapy (such as serious persistent toxicity or severe hypersensitivity to platinum agents or she declines standard of care)
Patients with ovarian cancer can be platinum-sensitive (with documented progression > 6 months after completion of a platinum containing regimen) or platinum resistant (progression < 6 months after completion of a platinum containing regimen)
PHASE II SCLC: Have received and progressed during or after a platinum-based standard chemotherapy regimen and/or an immune-checkpoint inhibitor
UROTHELIAL CARCINOMA EXPANSION COHORT: Patient must have received at least one platinum based regimen of chemotherapy and/or an immune-checkpoint inhibitor if appropriate with progressive disease
Patients must have received at least one prior platinum-based chemotherapy for locally advanced or metastatic disease; prior bevacizumab as 1st line and/or maintenance therapy is allowed; prior nivolumab is allowed
Advanced (metastatic or recurrent) pathologically proven urothelial carcinoma which is refractory to platinum based due to disease progression on a platinum containing regimen; patients progressing within 12 months of their last dose of platinum-based neoadjuvant or adjuvant chemotherapy will be considered platinum refractory
Patient must have failed or found to be intolerant of standard frontline platinum-based regimens and must not have received > 2 prior lines of therapy (nota bene [NB]: retreatment with a platinum-based doublet for sensitive relapse counts as another line therapy; however substitution of cisplatin with carboplatin or vice versa due to toxicity does not count as a separate regimen)
Patients whose tumors are deemed to be platinum-refractory will be excluded from the trial
Phase I/IB (pre-treated): have progression from at least one prior line of therapy; maintenance therapy following platinum doublet-based chemotherapy is not considered as a separate regimen of therapy; subjects who received platinum-containing adjuvant, neoadjuvant or definitive chemoradiation therapy given for locally advanced disease, and developed recurrent (local or metastatic) disease within 6 months of completing therapy are eligible for these arms; subjects with recurrent disease >= 6 months after completing a platinum-containing adjuvant, neoadjuvant or definitive chemoradiation therapy given for locally advanced disease, who also subsequently progressed during or after a systemic regimen given to treat the recurrence, must have received another treatment in the first-line metastatic setting
Must be resistant to platinum-based chemotherapy (defined as progression on or after platinum-based chemotherapy given in the recurrent/metastatic setting).
Inclusion Critera\n\n          1. Female ? 18 years of age\n\n          2. Histologically proven diagnosis of:\n\n             a. Endometrial and other uterine cancers with tumors of all histologies i. Recurrent\n             Stage I to II endometrial and other uterine cancers, after at least one prior line of\n             standard therapy, requiring further treatment with platinum-based chemotherapy ii.\n             Advanced Stage III to IV endometrial and other uterine cancers requiring treatment\n             with platinum-based chemotherapy b. Ovarian Cancer: Platinum-sensitive or\n             platinum-resistant recurrent or metastatic ovarian, fallopian, or primary peritoneal\n             cancer treated with at least one prior line of platinum-based chemotherapy and\n             requiring further treatment.\n\n             Platinum-sensitive is defined as cancer progression ? 6 months after platinum-based\n             chemotherapy. Platinum-resistant is defined as cancer progression < 6 months after\n             platinum-based chemotherapy.\n\n             Histologic cell types eligible are endometrioid adenocarcinoma, serous adenocarcinoma,\n             undifferentiated carcinoma, clear cell adenocarcinoma, mixed epithelial carcinoma,\n             adenocarcinoma not otherwise specified. c. Cervical cancer: recurrent or metastatic\n             cervical cancer that is not amenable to curative treatment with surgery and/or\n             radiation therapy and has not been previously treated with chemotherapy for\n             recurrence.\n\n             Histologic cell types eligible are squamous cell carcinoma, adenosquamous carcinoma or\n             adenocarcinoma\n\n          3. Have measureable disease defined by RECIST 1.1 confirmed by CT or MRI scan within 28\n             days of enrollment.\n\n          4. Life expectancy of ? 3 months at the time of enrollment.\n\n          5. Able to take orally administered study medication.\n\n          6. Have adequate baseline function and performance status within 28 days of enrollment:\n\n               1. Bone marrow function: absolute neutrophil count (ANC) ? 1,500/mm3, platelets ?\n                  100,000/mm3\n\n               2. Renal function: creatinine ? 1.5 x institutional upper limit normal (ULN) or if\n                  creatinine is > 1.5 x ULN, creatinine clearance must be > 50 mL/min.\n\n               3. Hepatic function: bilirubin ? 1.5 x ULN or ? 3.0 x ULN for subjects with Gilbert\n                  Syndrome; AST and ALT ? 3.0 × ULN.\n\n               4. Coagulation profile: international normalized ratio (INR) is ? 1.5 and an aPTT or\n                  PTT < 1.2 x ULN\n\n               5. ECOG performance ? 2\n\n          7. Women of child-bearing potential must agree to use contraceptive measures starting 1\n             week before C1D1 until 4 weeks after the last dose of study treatment and have a\n             negative serum pregnancy test within 28 days of enrollment.\n\n          8. Provide written informed consent and authorization permitting release of Protected\n             Health Information.\n\n          9. Ability and willingness to comply with the study protocol for the duration of the\n             study and with follow-up procedures.\n\n        Exclusion Criteria\n\n          1. Serious, non-healing wound, ulcer or bone fracture.\n\n          2. Major surgical procedure within 28 days or minor surgical procedure performed within 7\n             days prior to C1D1 (a major surgical procedure is defined as requiring general\n             anesthesia).\n\n          3. (Intentionally left blank)\n\n          4. Active bleeding or pathologic conditions that carry high risk of bleeding, such as\n             known bleeding disorder, coagulopathy, or tumor involving major vessels.\n\n          5. History or evidence upon physical examination of central nervous system (CNS) disease\n             including primary brain tumor; seizures not controlled with standard medical therapy;\n             and history of cerebrovascular accident (CVA, stroke), transient ischemic attack\n             (TIA), or subarachnoid hemorrhage within 6 months of enrollment.\n\n             a. Subjects with metastatic CNS tumors may participate in this study if the subject is\n             > 28 days from therapy completion (including radiation and/or surgery), is clinically\n             stable at the time of study enrollment, and is not receiving corticosteroid therapy.\n\n          6. Proteinuria on urinalysis within 28 days of enrollment. Subjects discovered to have a\n             urine protein of 1+ on dipstick or ? 30 mg/dl at baseline should undergo a 24-hour\n             urine collection and demonstrate < 1000 mg protein per 24 hours or spot urine protein\n             (mg/dL) to creatinine (mg/dL) ratio must be <1.0 to allow participation in the study.\n\n          7. Clinically significant cardiovascular disease including uncontrolled hypertension;\n             myocardial infarction or unstable angina within 6 months prior to enrollment; New York\n             Heart Association (NYHA) Grade II or greater congestive heart failure (Appendix E);\n             serious cardiac arrhythmia requiring medication; and Grade II or greater peripheral\n             vascular disease.\n\n          8. Women who are pregnant or nursing.\n\n          9. (Intentionally left blank)\n\n         10. Clinically significant, uncontrolled hypokalemia, hypomagnesaemia, and/or\n             hypocalcaemia.\n\n         11. Hemoptysis within 3 months prior to enrollment.\n\n         12. Acute or chronic liver disease, active hepatitis A or B with known cirrhosis or liver\n             dysfunction.\n\n         13. Cytotoxic chemotherapy, immunotherapy, or radiotherapy within 28 days (42 days in\n             cases of mitomycin C, nitrosourea, lomustine) prior to enrollment.\n\n         14. Concomitant treatment with strong inhibitors or inducers of CYP3A4, CYP2C9 and CYP2C19\n             within 14 days prior to enrollment and during the study unless there is an emergent or\n             life-threatening medical condition that required it.\n\n         15. Known history of human immunodeficiency virus infection (HIV).\n\n         16. Active bacterial infections requiring systemic antibiotics (excluding uncomplicated\n             urinary tract infection).\n\n         17. Other invasive malignancies, with the exception of non-melanoma skin cancer, who had\n             (or have) any evidence of other cancer present within the last 5 years prior to\n             enrollment or whose previous cancer treatment contraindicates this protocol therapy.\n\n         18. History of non-malignant gastrointestinal bleeding, gastric stress ulcerations, or\n             peptic ulcer disease within the past 3-months prior to enrollment that in the opinion\n             of the investigator may place the subject at risk of side effects on an\n             anti-angiogenesis product.\n\n         19. History of significant vascular disease (e.g. aortic aneurysm, aortic dissection).\n\n         20. Intra-abdominal abscess within the last 3 months of enrollment.\n\n         21. Pre-existing uncontrolled hypertension as documented by two baseline blood pressure\n             readings taken at least five minutes apart, defined as systolic BP >160 mm Hg or\n             diastolic BP > 90 mm Hg pressure.\n\n         22. QTc > 470 msec on screening ECG per Fridericia's formula.\n\n         23. History of or existing risk factors for Torsades de pointes (TdP) (e.g., heart\n             failure, hypokalemia, family history of Long QT Syndrome).\n\n         24. Concurrent use of concomitant medications that prolong the QT/QTc interval.\n\n         25. Baseline echocardiogram (within 56 days of enrollment) with left ventricular ejection\n             fraction (LVEF) < 50%.\n\n         26. History of difficulty swallowing, malabsorption, active partial or complete bowel\n             obstruction, or other chronic gastrointestinal disease or condition that may hamper\n             compliance and/or absorption of AL3818.\n\n         27. History of pancreatitis; history of renal disease that includes histologically\n             confirmed glomerulonephritis, biopsy proven tubulointerstitial nephritis, crystal\n             nephropathy or other renal insufficiencies.\n\n         28. Treatment with an investigational agent within 28 days of enrollment.\n\n         29. Known recreational substance abuse.\n\n         30. Anticoagulation therapy with warfarin. Subjects treated with heparin, low molecular\n             weight heparin, or any other anticoagulant may be included provided the subject has\n             been on a stable therapeutic dose of the anticoagulant for at least 14 days prior to\n             enrollment.\n\n         31. Known hypersensitivity to AL3818 or components of the formulation.
Patients diagnosed with platinum-refractory metastatic urothelial cancer that is measurable based on Response Evaluation Criteria in Solid Tumors (RECIST) criteria 1.1; platinum-refractory disease is defined as progressive disease on cisplatin or carboplatin therapy or within 12 months of prior platinum treatment (last dose)
PHASE I:\r\n* Patients must have received at least one course of platinum-based chemotherapy for the management of primary disease including carboplatin, cisplatin, or another platinum compound; this initial treatment may have included intraperitoneal therapy, consolidation, biologic/targeted agents, or extended therapy administered after surgical or non-surgical assessment\r\n* There are no restrictions on the total number of prior regimens patients may have received
Pre-operative (neo-adjuvant) platinum based or other chemotherapy
Patients are on treatment with a first line platinum-based (cisplatin, carboplatin or oxaliplatin) regimen for metastatic pancreas cancer, have received a minimum of 16 weeks of continuous platinum treatment and have no evidence of progression based on investigator's opinion.
Patients who have received platinum as potentially curative treatment for a prior cancer (eg ovarian cancer) or as adjuvant/neoadjuvant treatment for pancreas cancer are eligible provided at least 12 months have elapsed between the last dose of platinum-based treatment and initiation of the platinum-based chemotherapy for metastatic pancreas cancer.
Progression of tumour between start of first line platinum based chemotherapy for metastatic pancreas cancer and randomisation.
For Part I: patients with known contraindications to platinum agents are excluded
Not received more than 2 prior systemic therapies- one of which must have been a platinum based regimen- for primary or recurrent disease
Have been treated with debulking surgery and a first-line platinum-based chemotherapy regimen
Must have relapsed radiographically between 6 months and 36 months of completion of first-line platinum chemotherapy and should be randomized within 16 weeks of radiographic relapse
Patients must have had one prior platinum-based chemotherapeutic regimen for management of ovarian, primary peritoneal, or fallopian tube carcinoma and at least two prior chemotherapy regimens
ARM B COHORT 2: Patients must have failed treatment with platinum based therapy with or without cetuximab; previous therapy with a platinum concurrent with radiation followed by progression of disease within 6 months will count as failure of one prior line of cisplatin based therapy
Subjects with both platinum-sensitive and platinum-refractory disease will be eligible
PRIOR THERAPY:\r\n* Patients must have had at least one prior taxane-platinum-based chemotherapeutic regimen for management of primary disease; the platinum could be carboplatin or cisplatin; the taxane could be paclitaxel, docetaxel, or nab-paclitaxel\r\n* Patients must have had a treatment-free interval following last line platinum-based therapy of less than 12 months, have progressed during platinum-based therapy, or had persistent disease after a platinum-based regimen\r\n* Patients may have received hormonal therapy for treatment of recurrent disease; this will not be counted as a cytotoxic regimen\r\n* Initial treatment may have included non-cytotoxic agents (biologic/targeted agents, such as bevacizumab)\r\n* Patients are allowed to have received prior therapy with tumor vaccines, immune checkpoint blockade (except anti-CTLA-4), or other cancer immunotherapy\r\n* Patients may not have previously received treatment with a PARP inhibitor
PHASE II STUDY COHORT 1 OVARIAN CANCER ELIGIBILITY CRITERIA (MEDI+O, MEDI+C AND MEDI+O+C): MEDI+O and MEDI+C: Patients must have histologically or cytologically confirmed persistent or recurrent ovarian, fallopian tube, or primary peritoneal cancer who are either platinum-sensitive, platinum resistant or refractory during or after a first platinum containing regimen; for platinum-sensitive recurrent disease, the patients must have received at least two prior regimens prior to study enrollment
PHASE II STUDY COHORT 1 OVARIAN CANCER ELIGIBILITY CRITERIA (MEDI+O, MEDI+C AND MEDI+O+C): MEDI+O+C: Patients must have histologically or cytologically confirmed persistent or recurrent non-mucinous epithelial ovarian, fallopian tube, or primary peritoneal cancer who are either platinum-sensitive, platinum resistant or refractory during or after a first platinum containing regimen; for platinum-sensitive recurrent serous epithelial ovarian cancer, the patients must have received at least two prior regimens prior to study enrollment
At least one but no more than three prior lines of therapy in the advanced stage are allowed. One prior line of therapy must be platinum doublet chemotherapy.
Patients must have platinum-sensitive recurrent high-grade serous or high-grade endometrioid ovarian, primary peritoneal, or fallopian tube cancers; patients with other (clear cell, mixed epithelial, undifferentiated carcinoma, or transitional cell carcinoma) high-risk histologies are also eligible, provided that the patient has a known deleterious germline BRCA1 or BRCA2 mutation identified through testing at a clinical laboratory; Note: Due to the long acceptance of germline BRCA testing through Myriad, Myriad testing will be accepted; if testing for germline BRCA is done by other organizations, documentation from a qualified medical professional (e.g., ovarian cancer specialty physician involved in the field, high risk genetics physician, genetics counselor) listing the mutation and confirming that the laboratory results showed a recognized germline deleterious BRCA1 or BRCA2 mutation or BRCA rearrangement is required; please collect a copy of Myriad or other BRCA mutational analysis (positive or VUS or negative) reports\r\n* Platinum-sensitive disease defined as no clinical or radiographic evidence of disease recurrence for > 6 months (or 182 days) after last receipt of platinum-based therapy\r\n* Patients must have had a complete clinical response to their prior line of platinum therapy and cannot have had progression through prior platinum-based therapy
Prior therapy:\r\n* Prior chemotherapy must have included a first-line platinum-based regimen with or without intravenous consolidation chemotherapy\r\n* Patients may have received an unlimited number of platinum-based therapies in the recurrent setting\r\n* Patients may have received up to 1 non-platinum-based line of therapy in the recurrent setting; prior hormonal therapy will not be considered to count as this non-platinum-based line\r\n* Patients may not have had a prior anti-angiogenic agent in the recurrent setting; prior use of bevacizumab in the upfront or upfront maintenance setting is allowed\r\n* Patients may not have previously received a poly adenosine diphosphate (ADP) ribose polymerase (PARP)-inhibitor\r\n* Prior hormonal-based therapy for ovarian, primary peritoneal, or fallopian tube cancer is acceptable
Patients must have completed front-line taxane/platinum-based therapy of their primary tumor with a progression free interval of greater than 6 months from last therapy and measurable relapsed disease must be present in the abdomen greater than 1 cm
No evidence of progression on a platinum agent (e.g. carboplatin or cisplatin) or within 8 weeks of stopping platinum
Prior progression on or within 8 weeks of the last dose of a platinum agent (i.e. cisplatin or carboplatin) for recurrent or metastatic disease
Adults with histologically proven solid tumor for which a PD-1 or a PD-L1 agent is indicated:\r\n* Non-small cell lung cancer who has failed at least 1 treatment regimen for metastatic or recurrent disease; patients must have received a prior platinum-containing regimen\r\n* Locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy or who have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy\r\n* Recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) who had disease progression on or after platinum-containing chemotherapy or following platinum-containing chemotherapy administered as part of induction, concurrent, or adjuvant therapy\r\n* Advanced renal cell carcinoma whose disease worsened during or after treatment with an anti-angiogenic agent\r\n* Unresectable or metastatic melanoma and disease progression following ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor
Patients who have not previously been treated with platinum-based based doublet chemotherapy and who, in the judgment of the investigator, have rapidly progressive disease such that serious complications may arise from disease progression within the next 12 weeks will be excluded
Documented progression of disease according to RECIST v1.1 following standard of care (e.g. platinum doublet).
Prior anthracycline, platinum salt, or taxane for any malignancy
First-line treatment with a standard platinum doublet chemotherapy regimen (carboplatin or cisplatin at standard dosing plus one of the following drugs at standard dosing: paclitaxel, docetaxel, vinblastine, vinorelbine, pemetrexed, or etoposide); patients who received platinum-based chemotherapy for localized lung cancer (either adjuvant chemotherapy following surgery or chemotherapy given in conjunction with definitive radiation) are eligible if their cancer has recurred within 6 months of platinum-based chemotherapy
Disease progression on platinum-doublet chemotherapy prior to enrollment
Pre-operative (neo-adjuvant) platinum based or other chemotherapy is not permissible.
Patients may have received prior post-operative platinum based chemotherapy as per standard of care.
Platinum resistant or refractory disease as per standard clinical and Gynecologic Oncology Group definition; patients have had a treatment-free interval of less than 6 months from last platinum-based treatment to recurrence or progression during platinum based therapy
Patients must have received at least one-prior platinum based chemotherapy regimen, to include cisplatin, carboplatin or other organoplatinum compound, for treatment of primary or recurrent ovarian, fallopian tube or primary peritoneal cancer
Hypersensitivity to platinum agents
Patients who have failed previous hemi-thoracic platinum therapy will be ineligible (“failed” is having disease recurrence =< 3 months)
Phase II: extensive stage small cell lung cancer with progression or recurrence after exactly one platinum-containing regimen. Patients who progressed during or within one month of completing platinum-based chemotherapy will be excluded. Patients who received primary curative chemoradiation therapy for limited disease, but who recur within the primary tumor site, previously radiated field or with distant metastases are also allowed to participate. Patients who have clinical evidence of recurrent small cell lung cancer do not require a confirmatory biopsy to be eligible for this trial. Prior irinotecan is not allowed.
Subjects that progressed during or within one month of completion of first-line platinum-based chemotherapy will be excluded.
Patients must have received at least one course of chemotherapy consisting of a platinum doublet and must have no acceptable standard treatment options
0-1 prior chemotherapy regimens for recurrent or advanced disease; platinum based chemotherapy administered as a radiation sensitizer agent is allowed and does not count as prior therapy
Prior treatment with platinum based doublet and checkpoint inhibitor
Patients must have had exactly one prior platinum/taxane-based chemotherapeutic regimen for management of primary disease, and must be in first relapse; first relapse must occur >= six months from completion of front-line platinum-based therapy; (time measured from last platinum dose; for example, patients receiving a biologic or chemotherapeutic agent after completion of platinum-based therapy as part of upfront therapy would be eligible based on time from last dose of platinum chemotherapy; in this situation, patients must be at least four weeks from last dose of a biologic agent); relapse cannot be based on rising cancer antigen (CA)- 125 alone; there must be radiographic evidence of recurrent disease
Histologically confirmed solid tumor malignancy for which platinum-based chemotherapy on a 21-day cycle or 14 day cycle is being recommended
progression or relapse during or within 6 months of the most recent treatment with a platinum-containing chemotherapy regimen
No more than 3 prior lines of cytotoxic chemotherapy for platinum-resistant disease
Completed first-line platinum-based chemotherapy and surgery with a response, in the opinion of the Investigator
Any prior treatment for ovarian cancer, other than the first-line platinum regimen
Have had no more than one prior platinum-based regimen for metastatic disease NOTE: Maintenance therapy received after initial chemotherapy will not be considered additional chemotherapy and will be allowed; and
Disease progression during or following treatment with at least one platinum-containing regimen (patients should have been treated for at least 2 cycles). In patients who received prior adjuvant/neoadjuvant platinum-containing chemotherapy, progression had to occur within 12 months of treatment.
Patients must have progressive disease following prior therapy; specifically, patients must have progressed on platinum-based chemotherapy
Subject has experienced disease progression on or after platinum-containing chemotherapy
Patients must have demonstrated progression on or intolerance to platinum-based chemotherapy
Inclusion:\n\n        All Patients:\n\n          1. Adequate organ function, determined by:\n\n             Absolute neutrophil count (ANC) ? 1.5 X10^9/L, Platelets ? 100 X10^9/L, Hemoglobin ?\n             9g/dL, aPTT ?1.5 x ULN, Total bilirubin ? 1.5 mg/dL, ALT and AST ? 2.5 x ULN if no\n             liver involvement or ? 5 x ULN with liver involvement, Creatinine < 1.5 x ULN\n             concurrent with creatinine clearance >50 mL/min.\n\n          2. Normotensive or well controlled blood pressure (<140/90).\n\n          3. ECOG perf. status of 0-1.\n\n          4. Ejection fraction (EF) > 50%\n\n          5. Toxicities from prior therapy greater than CTCAE Grade 1 have resolved with the\n             exception of alopecia. Patients with Grade ? 2 neuropathy are eligible.\n\n          6. Male patients must use two forms of contraception. Female partners of child-bearing\n             potential of male patients must use at least one of the two forms of acceptable\n             contraception. Female patients should not be breast-feeding and must have a negative\n             pregnancy test.\n\n          7. Patients with lymphoma must have documented analysis of bone marrow infiltration from\n             biopsy carried out < 3 months of enrollment, or be able to undergo a new bone marrow\n             biopsy if such procedure was performed > 3 months prior to enrollment.\n\n        Part 1a Dose Escalation: Histological or cytological confirmation of malignant solid tumor\n        or lymphoma that is refractory to standard therapy or for which no standard therapy exists.\n\n        Part 1b MTD Dose Expansion: Histologically or cytologically confirmed platinum-resistant or\n        platinum-refractory high grade serous ovarian cancer. Platinum-resistant disease is defined\n        by progression <6 months following the last administered platinum-based regimen, and\n        platinum-refractory is defined by lack of at least a partial response while on\n        platinum-containing regimens. Platinum sensitive disease (recurrent after 6 months) must\n        have been treated with additional platinum containing regimens or PARPi if tBRCAm+ or other\n        HRD+\n\n        Exclusion:\n\n          1. Chemotherapy, radiotherapy, hormonal therapy, immunotherapy or investigational drugs\n             <21 days or 5 half-lives (whichever is shorter).\n\n          2. More than 5 prior lines of treatment for an advanced solid tumor.\n\n          3. Major surgery ?21 days or minor surgery ?7 days.\n\n          4. Unable to swallow oral medicine or has a GI disorder that would jeopardize intestinal\n             absorption of AZD5153.\n\n          5. Any of the following: Drugs or other products known to be strong or moderate\n             inhibitors/inducers of CYP3A4/5, or CYP3A4/5 sensitive substrates or substrates with a\n             narrow therapeutic range. Drugs that are sensitive substrates of the transporters\n             P-gp, BCRP, OATP1B1, OAT3, MATE1 and MATE2K.\n\n             Herbal preparations, including but not limited to: St. John's wort, kava, ephedra (ma\n             huang), gingko biloba, dehydro-epiandrosterone, yohimbe, saw palmetto, and ginseng.\n\n             Drugs known to prolong QT interval or induce Torsades de Pointes\n\n          6. Refractory nausea and vomiting\n\n          7. Tuberculosis.\n\n          8. Live attenuated vaccine ?28 days.\n\n          9. Spinal cord compression or brain metastases unless asymptomatic, treated and stable\n             and not requiring steroids for at least 4 weeks prior to start.\n\n         10. Evidence of severe or uncontrolled systemic diseases, including uncontrolled\n             hypertension, active bleeding diatheses, or active infection, or other comorbidity\n             that renders the patient unsuitable.\n\n         11. Any of the following:\n\n             Mean resting corrected QT interval (QTcF) >450 msec obtained from 3 electrocardiograms\n             (ECGs).\n\n             Clinically important abnormalities in rhythm, conduction or morphology of resting ECG\n             e.g., complete left bundle branch block, third degree heart block.\n\n             Factors that increase the risk of QTc prolongation or risk of arrhythmic events such\n             as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT\n             syndrome or unexplained sudden death under 40 years of age.\n\n         12. Hypersensitivity to active or inactive excipients of AZD5153 or drugs with a similar\n             chemical structure.\n\n         13. Non-Hodgkin lymphoma (NHL) at high risk for developing tumor lysis syndrome are not\n             eligible for the dose escalation portion of this study.
Radiologically confirmed disease progression following two previous lines of anti-cancer therapy, one of which should be a platinum based regimen, OR the patient has refused treatment with approved treatment modalities
Histologically confirmed, measurable or non-measurable, recurrent or persistent, platinum-resistant epithelial ovarian, fallopian tube or primary peritoneal carcinoma. By standard Gynecologic Oncology Group (GOG) criteria, platinum-resistant disease is defined by a disease-free interval of less than 6 months following treatment with a platinum-based regimen, or the progression of disease during platinum-based therapy.
Previously treated with not more than 1 doublet or triplet regimen and that regimen contained gemcitabine and a platinum agent
Patients must not have received any other chemotherapeutic treatment for malignant mesothelioma other than pemetrexed and a platinum agent such as cisplatin.
Patients either may be treatment-naive and considered ineligible for cisplatin-based chemotherapy or have recurrent disease after any prior platinum-based chemotherapy regimen and meet at least one of the following criteria:\r\n* Glomerular filtration rate ? 30 mL/min and < 60 mL/min (by Cockcroft-Gault)\r\n* Grade 2 or higher hearing loss\r\n* Grade 2 or higher peripheral neuropathy\r\n* Eastern Cooperative Oncology Group (ECOG) performance status 2\r\n* OR have recurrent disease after any prior platinum-based chemotherapy regimen
Tumor progression within 6 months of platinum-based chemotherapy
Prior therapy with a platinum chemotherapy (e.g. cisplatin, carboplatin, oxaliplatin)
Patients must have failed platinum based therapy as well as cetuximab; if patients were found to be intolerant of standard first line systemic chemotherapy, patients are eligible to enroll to this study provided both cetuximab and cisplatin were administered prior to enrollment
Disease progression must be documented following platinum based chemotherapy; this can be in the recurrent or metastatic setting following platinum or in the concurrent setting provided progression has occurred within 6 months from the last dose of platinum
Have had at least one line of prior platinum-based systemic chemotherapy once diagnosed with recurrence or metastatic disease
At least one prior line of platinum-based chemotherapy (subjects are eligible for enrollment and leukapheresis while still platinum-sensitive, however, they must have developed platinum resistant disease for treatment (turnstile 2).
Patients may have previously failed non-platinum containing therapy or may never have previously progressed on treatment
Patients must be on treatment with platinum-based (cisplatin, oxaliplatin or carboplatin) treatment for locally advanced or metastatic pancreatic cancer and have received a minimum of 16 weeks of therapy without evidence of disease progression based on the investigator’s opinion\r\n* Discontinuation of the platinum component of the regimen for chemotherapy-related toxicity is permissible provided the patient has previously received at least 16 weeks of platinum-based therapy without evidence of disease progression =< 8 weeks after treatment with the platinum agent
Patients who have demonstrated resistance to platinum agents (e.g. oxaliplatin, cisplatin) are not eligible to participate in this study
Platinum resistant or refractory disease as defined by progression of disease on a platinum-containing regimen or recurrence of disease within 180 days of previous platinum treatment
For expansion cohort: metastatic platinum-refractory cervical cancer, or metastatic/recurrent platinum-refractory HPV-positive head and neck cancer (as determined by polymerase chain reaction (PCR), in situ hybridization (ISH), or p16 immunohistochemistry (IHC); platinum refractory is defined as recurrent disease within 6 months after receiving cisplatin or carboplatin with radiation for their newly diagnosed disease, or after receiving cisplatin or carboplatin for their recurrent/metastatic disease
At least 12 months have elapsed since platinum-based peri-operative treatment
Participant must have histologically or cytologically confirmed advanced or metastatic Small Cell Lung Cancer (SCLC) with documented first disease progression during or following front-line platinum-based systemic regimen
For the dose expansion cohort, participants must have histologically or cytologically confirmed diagnosis of either:\r\n* Ovarian, fallopian tube, or primary peritoneal cancer of high grade serous histology which has recurred despite standard therapy; up to 3 prior lines in the platinum resistant setting (i.e. up to 3 lines after patients have become platinum resistant); patients may have received unlimited lines while platinum sensitive\r\n* Triple-negative breast cancer (TNBC) which has recurred despite standard therapy; recurrent TNBC needs to have metastatic disease and patients with an in breast recurrence are not eligible; up to 4 prior lines in the recurrent setting for patients with triple-negative breast cancer are allowed
For the dose expansion cohort, patients with ovarian, fallopian tube or primary peritoneal cancer must have platinum resistant disease defined as progression within 6 months after last platinum regimen; platinum refractory disease is allowed
Women with epithelial ovarian, fallopian tube, or primary peritoneal carcinoma with platinum-resistant disease (defined as having relapsed within 6 months of last platinum-containing regimen because we would like to include both primary and secondary resistance); patients are allowed to have had more than 2 prior cytotoxic treatment regimens; all patients should have received standard of care agents, which confer clinical benefit
Participants must have received 4-6 cycles of platinum-based first-line chemotherapy and must have an ongoing response of complete response (CR), partial response (PR), or stable disease (SD) after completion of chemotherapy; acceptable combinations, as recommended per NCCN guidelines, include cisplatin or carboplatin combined with either etoposide or irinotecan\r\n* As an exception to the above criterion, participants receiving only 3 cycles of chemotherapy due to toxicity are eligible, if they have an ongoing PR or CR after the third (3rd) cycle\r\n* Participants who have received > 6 cycles of platinum-based first-line chemotherapy are not eligible
Participants must initiate study treatment with thoracic radiation therapy =< 8 weeks (56 days) from the last dose of platinum-based first line chemotherapy;\r\n* Thoracic radiation therapy must not be administered < 3 weeks (21 days) from the last dose of platinum-based first line chemotherapy\r\n* Ipilimumab/nivolumab study therapy must not be administered < 13 days and not more than 21 days from the last dose of thoracic radiotherapy
Subjects who have platinum-resistant disease; there is no limit on the number of prior treatment regimens
Participants must have had at least one prior platinum-based chemotherapeutic regimen for management of primary disease (e.g., a regimen containing carboplatin, cisplatin, or another organoplatinum compound); this initial treatment may have included intraperitoneal therapy, consolidation, biologic/targeted (non-cytotoxic) agents (e.g., bevacizumab) or extended therapy administered after surgical or non-surgical assessment
Participants must have recurrence within 12 months of their last platinum-containing regimen
Patients must be in their first platinum sensitive recurrence; this is defined as recurrence that occurred greater than six months after completion of first line platinum based therapy; for the phase 1 portion of the study, patients must have a platinum free interval between 6 months and 1 year and are not eligible or unwilling to undergo a second cytoreductive surgery
Patients should have recurrent platinum-resistant or- refractory disease - defined as disease that has progressed by imaging while receiving platinum or had recurrence within 6 months of the last receipt of platinum-based chemotherapy; rising CA125 only is not considered as platinum-resistant or refractory disease
No more than 3 prior treatment regimens (including primary therapy; no more than 1 prior non-platinum based therapy in the platinum-resistant/-refractory setting); hormonal therapies used as single agents (i.e. tamoxifen, aromatase inhibitors) will not count towards this line limit
Ovarian cancer patients must be resistant to platinum therapy; therapy (i.e. within 6 months of last platinum therapy); patients who received greater than two prior platinum containing regimens will not be eligible
Patient with progressive disease during first line chemotherapy with a platinum/taxane combination will be excluded
Participants must have primary or secondary platinum-resistant ovarian cancer.
Participants must have received prior platinum-based chemotherapy for management of\n             primary disease but must not have received more than 2 prior systemic cytotoxic\n             regimens.
Patients refractory to primary platinum therapy where \refactory\ is defined as\n             disease progression within 6 months of first dose of initial platinum-based therapy.
Participants with histologically or cytologically confirmed diagnosis of epithelial ovarian, primary peritoneal or fallopian tube cancer will be enrolled in this study; patients must have experienced recurrence or progression within 6 months after completion of platinum based chemotherapy (by Response Evaluation Criteria in Solid Tumors [RECIST] 1.1 criteria).
Patients whose ovarian cancer recurs/progresses within 0-6 months following platinum-based chemotherapy have platinum resistant disease; these patients are not considered to benefit from additional platinum-based therapy and are treated with other sequential single agents; such patients are eligible for this trial
Patients with documented disease recurrence/progression within 6-12 months of completing platinum-based therapy, are considered to have 'borderline' platinum sensitivity; these patients will not be eligible for this trial
Patients who relapse more than 12 months after completion of platinum-based treatment are considered 'platinum sensitive' and will not be eligible for this trial, since they have a favorable (33-59%) chance of responding to further rounds of platinum based chemotherapy
High grade serous ovarian cancer patients with either platinum refractory, platinum-resistant disease or platinum-sensitive disease are eligible; platinum refractory is defined as either relapse less than 2 months after the last platinum based therapy or relapse during platinum therapy; platinum-resistance is defined as relapse within 2 to 6 months after last dose of platinum-based chemotherapy; platinum sensitivity is defined as a relapse greater than 6 months after last dose of platinum-based chemotherapy; participants with platinum-sensitive disease must have progressed after receiving 2 prior platinum-based chemotherapy regimens
Disease progression on imaging or tumor marker progression (clinical significance of tumor marker progression to be decided per the discretion of treating physician) after at least 2 lines of platinum-based chemotherapies unless patient is ineligible for further platinum based chemotherapy or refuses second (2nd) line platinum based chemotherapy due to toxicity; for primary mediastinal germ cell tumors, failure of first-line chemotherapy will be accepted; prior high dose chemotherapy with hematopoietic stem cell rescue is allowed; prior treatment with bevacizumab is allowed
Patients must have had one prior platinum-based chemotherapeutic regimen for management of primary disease; patients are allowed to receive, but are not required to receive, two additional cytotoxic regimens for management of recurrent or persistent disease
Adult patients with documented deleterious BRCA 1 or 2 mutations with histologically confirmed ovarian, primary peritoneal, breast, prostate, pancreas, gastric or other solid tumor whose disease has progressed following at least one standard therapy or who have no acceptable standard treatment options; patients with ovarian cancer should have one prior platinum-based chemotherapeutic regimen for management of primary disease containing carboplatin, cisplatin, or another organoplatinum compound; this initial treatment may have included intraperitoneal therapy, consolidation, biologic/targeted (non-cytotoxic) agents or extended therapy administered after surgical or non-surgical assessment; ovarian cancer patients with both platinum-sensitive and platinum-resistant disease are eligible; patients with platinum-refractory disease are NOT eligible; definitions:\r\n* Platinum sensitive ovarian cancer is defined as patients who respond to platinum-based therapy (complete or partial) and then progress/recur more than 6 months after their last platinum dose (i.e., platinum-free interval is > 6 months)\r\n* Platinum resistant ovarian cancer is defined as patients who respond to platinum-based therapy (complete or partial) and then progress/recur within 6 months of their last platinum dose (i.e., platinum-free interval is =< 6 months)\r\n* Platinum refractory ovarian cancer is defined as patients who have progression of disease while receiving platinum-based chemotherapy or who fail to achieve at least a partial response to platinum-based chemotherapy (i.e., best response to platinum-based chemotherapy is stable disease)
Patients with prior treatment with platinum-based chemotherapy
Patients will be limited to:\r\n* >= 70 years of age, OR\r\n* With co-morbidities that preclude treatment with standard platinum-based chemotherapy, as determined by the treating physician, OR\r\n* Karnofsky performance scale (KPS) =< 80, OR\r\n* Creatinine clearance < 30 cc/min
Patients must have platinum-resistant ovarian cancer, defined as progression within 6 months from completion of a minimum of four cycles of platinum-containing therapy.
Patients with primary platinum-refractory disease
Patients must have had a complete response to front-line platinum-taxane therapy (at least three cycles)
All patients must have also had a treatment-free interval without clinical evidence of progressive disease of at least 6 months from completion of front-line chemotherapy (both platinum and taxane); front-line therapy may have included a biologic agent (i.e. bevacizumab)
A single dose of a platinum doublet discontinued due to intolerability without evidence of disease progression is permitted
Histologically confirmed small-cell lung cancer (SCLC) with documented disease progression after at least 2 prior systemic regimens, including at least one platinum-based regimen
Prior platinum chemotherapy or immunotherapy
1a. Head and Neck Stage III/IV squamous cell carcinoma; Tumor progression or recurrence within 6 months of last dose of platinum therapy in the adjuvant, primary, recurrent or metastatic setting (or within 9 months if the patient received > 1 platinum-based chemotherapy regimen in the metastatic setting). Active brain metastases or leptomeningeal metastases are excluded; nasopharyngeal cancer, confirmed recurrent or metastatic carcinoma of the nasopharynx and salivary gland or non-squamous histologies are also excluded.
Subjects who have received at least 1 prior platinum-based therapy. Subjects who have a non-platinum-based regimen may be enrolled with medical monitor approval.
Metastatic or locally advanced and not amenable to curative therapy with disease progression on or after platinum-based chemotherapy or alternative therapy if platinum-based therapy is not appropriate.
Subjects must have received a platinum-taxane-based regimen as first-line therapy.
Must have progression on or after therapy containing platinum/fluoropyrimidine or refused standard therapy.
Progressed or recurred within 12 months of completing platinum therapy or received > 1 prior line of platinum therapy for breast cancer in any setting (adjuvant or neoadjuvant).
Subjects who had objective disease progression while receiving platinum chemotherapy administered for locally advanced or metastatic disease; subjects who received low-dose platinum therapy administered in combination with radiation therapy are not excluded
Subjects who have received platinum in the adjuvant or neoadjuvant setting are eligible; however, subjects may not have relapsed within 6 months of the last dose of prior platinum therapy
Patients must have had one prior platinum-based chemotherapeutic regimen for management of primary disease containing carboplatin, cisplatin, or another organoplatinum compound; this initial treatment may have included intraperitoneal therapy, consolidation, non-cytotoxic agents (biologic/targeted agents, such as bevacizumab) or extended therapy administered after surgical or non-surgical assessment; if patients were treated with paclitaxel for their primary disease, this can have been given weekly or every 3 weeks
Patients who have received only one prior cytotoxic regimen (platinum-based regimen for management of primary disease), must have a platinum-free interval of greater than 6 months
Neoadjuvant platinum-based chemotherapy with recurrence >12 months from completion of therapy is permitted.
Adjuvant platinum-based chemotherapy following radical cystectomy with recurrence >12 months from completion of therapy is permitted.
Patients must be candidates for platinum based chemotherapy and previously untreated
Patients must have any epithelial (ie, serous, endometroid, mucinous, clear cell) ovarian, fallopian tube, or primary peritoneal cancer. Patients must have experienced a response lasting at least 6 months to first-line platinum-based therapy but currently considered to have platinum-resistant disease per investigator's assessment (e.g, patient is not eligible for further platinum containing treatment). Patients may have received up to 5 lines of cytotoxic therapy for advanced or metastatic cancer. Neoadjuvant and adjuvant therapies are not counted towards lines of therapy.
Patients must have with high-grade serous or endometroid ovarian, fallopian tube, or primary peritoneal cancer. Patients must have experienced a response lasting at least 6 months to first-line platinum-based therapy but currently considered to have platinum-resistant disease per investigator's assessment (e.g, patient is not eligible for further platinum containing treatment). Patients may have had up to 4 lines of cytotoxic therapy for advanced or metastatic cancer. Neoadjuvant, adjuvant, and the combination of both will be considered as one line of therapy.
Patients with primary platinum refractory ovarian cancer (ie, progressive disease on or within 6 months of first-line platinum therapy)
Patients must have histologically diagnosed high-grade (Grade 2 or 3) serous epithelial ovarian, fallopian tube, or primary peritoneal cancer with recurrent disease and must have been previously treated with chemotherapy and experienced a response lasting at least 6 months to first-line platinum based therapy.
Platinum resistant/refractory disease, defined as disease progression within 180 days following the last administered dose of platinum therapy (resistant), or lack of response or disease progression while receiving the most recent platinum based therapy (refractory), respectively.
Received up to 3 lines of systemic anticancer therapy for platinum sensitive disease, most recently platinum containing, and no prior systemic therapy for platinum resistant disease
Had disease progression while on a platinum containing regimen in the first-line setting or within 14 months after completing the first-line platinum regimen. Participants who received treatment with one immune checkpoint inhibitor regimen are eligible (for example PD-1, PDL1, or CTLA4) and may have a longer interval since prior platinum-containing therapy (?24 months).
previously received at least 1 but no more than 2 lines of therapy, one therapy must have included a platinum based regimen
Subjects may have had any number of prior chemotherapy, endocrine therapy, immunologic, or biologic regimens for metastatic breast cancer; treatment with prior platinum compounds (except cisplatin) is allowed as long as it has been 6 months or more since exposure to prior platinum; prior cisplatin treatment is allowed IF it was given in the adjuvant setting
Disease Progression between 6-24 months after a first or second platinum based regimen
Prior hypersensitivity to platinum chemotherapy or to any of the excipients of platinum or nivolumab therapy
Must have received prior treatment with a platinum-based therapy
Phase 1: Individuals with epithelial ovarian cancer, fallopian tube carcinoma, or primary peritoneal carcinomas who are considered to have platinum-resistant disease (progression within 6 months from completion of platinum-based chemotherapy).
Phase 2: Individuals with epithelial ovarian cancer, fallopian tube carcinoma, or primary peritoneal carcinomas who are considered to have platinum-resistant disease (progression within 6 months from completion of a minimum of 4 platinum therapy cycles).
Platinum-refractory disease (progression during the first platinum-based chemotherapy)
Patients must be platinum-resistant (platinum-free interval < 6 months) or have platinum-refractory disease as per Gynecologic Cancer Intergroup Committee (GCIC) criteria; disease progression has to be radiologic or clinical; biomarker progression with CA125 after a platinum based regimen would not be sufficient evidence of disease progression; the patients must have had radiological progression to that regimen
Received first-line treatment with a platinum-based regimen and had no evidence of disease progression for >= 6 months after the last dose
Received second-line treatment with a platinum-based regimen, with progression of disease after attaining a response
Progression of disease based on imaging after the second-line platinum-based regimen (individuals treated with a pegylated liposomal doxorubicin-containing regimen as a second-line therapy are eligible if subsequent disease progression occurs >=9 months from the first dose)
Patients must have previously received a platinum and paclitaxel containing regimen
Patients may have either platinum sensitive or platinum resistant recurrent ovarian cancer
Histologically confirmed recurrent ovarian, fallopian tube or primary peritoneal carcinoma or endometrial cancer in post-menopausal women; NOTE: pure clear cell and pure mucinous carcinomas are ineligible; platinum sensitive, platinum resistant and platinum refractory disease are eligible; no limitations in the number of prior regimens
Treatment with prior platinum therapy
Patients must have received at least 2 prior platinum based lines of chemotherapy - Patients must be partially platinum sensitive or platinum sensitive
Patients who have platinum resistant or refractory disease
Inclusion Criteria:\n\n        Disease status\n\n          -  Parts A and B/B2: Histologically or cytologically confirmed advanced solid tumor that\n             is metastatic or unresectable and for which standard curative or palliative measures\n             do not exist or are no longer effective, or for whom regimens containing gemcitabine,\n             cisplatin, etoposide, and/or irinotecan might be considered, and with measurable\n             disease according to RECIST criteria\n\n          -  Part C1:\n\n        For Pre-screening:\n\n          -  Advanced (metastatic or locally-advanced unresectable and not eligible for definitive\n             treatment, e.g., surgery/radiotherapy), histologically confirmed non-small cell lung\n             cancer (NSCLC)\n\n          -  Available historical tumor specimen at the time of pre-screening or willing to provide\n             a tumor biopsy (core) if the biopsy may be considered as part of standard clinical\n             practice for the participant\n\n          -  Received or did not tolerate standard approved targeted therapy, if appropriate for\n             tumor genotype\n\n        For Screening:\n\n          -  Measurable disease according to RECIST criteria\n\n             -Part C2:\n\n          -  Advanced (locally-advanced incurable or metastatic) histologically confirmed estrogen\n             receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2)\n             negative breast cancer.\n\n          -  Adequate available historical tumor specimen or willing to provide a tumor biopsy\n             (core) if the biopsy may be considered as part of standard clinical practice for the\n             participant\n\n          -  Measurable disease according to RECIST criteria\n\n             -Part C3:\n\n          -  Advanced (locally-advanced incurable or metastatic) histologically confirmed SCLC that\n             is platinum-resistant, defined as disease progression during initial treatment with a\n             platinum-based regimen or progression within 90 days of completion of platinum\n             therapy. Participants with platinum-resistant disease may receive a second-line\n             non-platinum-based chemotherapy and subsequently be enrolled to this study.\n             Participants who received and are resistant to a second-line platinum-based\n             chemotherapy may also be enrolled into the study.\n\n          -  Adequate available historical tumor specimen or willing to provide a tumor biopsy\n             (core) if the biopsy may be considered as part of standard clinical practice for the\n             participant\n\n          -  Measurable disease according to RECIST criteria\n\n          -  WHO performance status of 0 or 1\n\n          -  Life expectancy of >=12 week\n\n          -  Hematological and biochemical indices within protocol specified ranges at screening.\n\n        Exclusion Criteria:\n\n          -  Radiotherapy (except for palliative reasons) endocrine therapy, immunotherapy, or\n             chemotherapy during the previous 4 weeks (6 weeks for nitrosoureas and Mitomycin-C,\n             and 4 weeks for investigational medicinal products) or less than 4 drug half-lives,\n             whichever greater, before first dose of study drug.\n\n          -  Parts A, B and B2:\n\n               -  Greater than 6 cycles of prior treatment with cisplatin and/or carboplatin.\n\n                    1. Part A/B: History of prior dose reductions or dose interruptions while\n                       receiving cisplatin or carboplatin due to toxicity from the platinum or\n                       intolerance to either agent.\n\n                    2. Part B2: Prior exposure to irinotecan is permitted except for participants\n                       with a known hypersensitivity reaction to irinotecan.\n\n               -  Participants with a known history of Grade 4 thrombocytopenia or Grade 4\n                  neutropenia while receiving prior therapy.\n\n          -  Part C1:\n\n               -  Any cytotoxic chemotherapy beyond 1 line of platinum-based chemotherapy. One\n                  additional line of non-platinum based therapy in the advanced setting\n\n                    1. Pre-screening Only*: Participants may currently be receiving platinum-based\n                       chemotherapy in the advanced setting, or have completed 1 line of\n                       platinum-based chemotherapy and are currently receiving a second-line\n                       non-platinum-based therapy or maintenance therapy\n\n                    2. There is no restriction on prior immunotherapy or targeted therapy unless\n                       combined together with a cytotoxic agent\n\n               -  Any prior gemcitabine for the treatment of NSCLC in any setting within 6 months\n\n               -  Participants who are known to be TP53 wild-type, unless they are determined to\n                  have ATM loss of expression during screening or pre-screening or until all the\n                  planned participants with TP53 mutation are enrolled as determined by the medical\n                  monitor\n\n               -  Participants with unknown TP53 mutational status will be enrolled until the group\n                  of approximately 10 participants without TP53 mutation or until all the planned\n                  participants with TP53 mutation are enrolled as determined by the medical monitor\n\n          -  Part C2:\n\n               -  Any prior platinum therapy in the adjuvant or neoadjuvant within 6 months of\n                  screening\n\n               -  Relapse within 3 months of completion of prior adjuvant or neoadjuvant\n                  chemotherapy\n\n               -  Any prior chemotherapy in the metastatic setting with the exception of either a\n                  taxane or an anthracycline in the first-line metastatic setting\n\n                  (a) There is no restriction on prior immunotherapy or targeted therapy in the\n                  metastatic setting unless combined together with a cytotoxic agent\n\n               -  Participants with known BRCA1/BRCA2 germline mutations, either determined and\n                  documented prior to Screening, or determined during Screening. Participants with\n                  unknown BRCA1/BRCA2 status may be enrolled at discretion of the sponsor\n\n               -  Participants who are documented to be non-basaloid subtype using molecular\n                  profiling assay (e.g. PAM50 assay) prior to Screening\n\n               -  Participants with unknown BRCA1/BRCA2 or basaloid subtype status will be enrolled\n                  until the number of enrolled participant is approximately 40. If approximately 40\n                  participants have been enrolled and a minimum of 30 participants who are basaloid\n                  positive and BRCA1/BRCA2 germline wild-type have not been enrolled, the basaloid\n                  subtype and BRCA status assay will be required at Screening to exclude\n                  participants who are basaloid negative or have BRCA1/BRCA2 germline mutations.\n\n          -  Part C3:\n\n               -  Prior platinum-sensitive participants , unless they progress on or within 90 days\n                  of completion of platinum-based regimen\n\n               -  There is no restriction on prior immunotherapy or targeted therapy in the\n                  metastatic setting unless combined together with a cytotoxic agent\n\n               -  During prior carboplatin therapy, requirement for dose reduction below AUC 5\n                  mg.min/mL or discontinuation of carboplatin for toxicity or lack of tolerability.\n\n          -  Unresolved toxicity of Common Terminology Criteria for Adverse Events (CTCAE) Grade 2\n             or greater from previous anti-cancer therapy or radiotherapy\n\n          -  History of spinal cord compression or brain metastases, unless asymptomatic, treated,\n             stable, and not requiring treatment with steroids for at least 4 weeks before first\n             dose of study drug. Any history of leptomeningeal metastases.\n\n          -  Female participants who are already pregnant or lactating, or plan to become pregnant\n             within 6 months of the last dose of study drug are excluded. Female participants of\n             childbearing potential must adhere to contraception guidelines\n\n          -  Male participants with partners of child-bearing potential must agree to adhere to\n             contraception guidelines. Men with pregnant or lactating partners or partners who plan\n             to become pregnant during the study or within 6 months of the last dose of study drug\n             are excluded\n\n          -  Serious cardiac or other co-morbid disease, as specified in the protocol\n\n          -  Prior bone marrow transplant or extensive radiotherapy to greater than 15% of bone\n             marrow\n\n          -  Part C:\n\n               -  Current malignancies of other types, with the exception of adequately treated\n                  cone-biopsied in situ carcinoma of the cervix uteri and basal or squamous cell\n                  carcinoma of the skin\n\n          -  Major surgery =<2 weeks before starting study drug, or incomplete recovery from a\n             prior major surgical procedure.
Has received prior therapy with at least 1 platinum-containing regimen
Any number of prior lines of systemic therapy may have been received for advanced (recurrent, locally advanced, or metastatic) SCC of the lung, but at least one must have been a platinum-based chemotherapy regimen. Platinum therapy may be given on-label or as part of a clinical trial.
Tumor progression or recurrence within 6 months of last dose of platinum therapy in the primary treatment setting
Patients must have had one prior platinum-based chemotherapeutic regimen for management of primary disease.
Patients must have had one prior platinum-based chemotherapeutic regimen for management of primary disease containing carboplatin, cisplatin, or another organoplatinum compound; this initial treatment may have included intraperitoneal therapy, high-dose therapy, consolidation, or extended therapy administered after completion of initial chemotherapy; patients must be considered platinum resistant or refractory according to standard Gynecologic Oncology Group (GOG) criteria, i.e., have had a treatment-free interval following platinum of less than 6 months, have persistent disease at the completion of primary platinum-based therapy or have progressed during platinum-based therapy; patients with greater than 6 month disease free interval after completion of primary therapy must have received a second platinum based regimen, and have persistent or progressive disease, or disease that recurs within 12 months of completion of second line platinum-based therapy; patients who are unable to receive platinum-based therapy for recurrent disease would also be eligible
Progression or recurrence of urothelial carcinoma following one prior platinum containing chemotherapy regimen for metastatic or unresectable locally advanced disease. A participant who receives a neoadjuvant or adjuvant platinum-containing regimen following cystectomy for localized muscle-invasive urothelial carcinoma is acceptable (without further systemic treatment), if recurrence/progression occurs ? 12 months following completion of therapy.
No more than 2 prior lines of anti-cancer therapy, one of which must have included pemetrexed and a platinum.
Patients must have platinum-resistant disease, (defined as progression within < 6 months from completion of a minimum of 4 platinum therapy cycles (+ 7 days); the date should be calculated from the last administered dose of platinum therapy)
Cohort A: Has received 0 to 2 additional prior lines for treating ROC (or 1-3 total prior lines counting the front line) and must have a platinum-free interval (PFI) of ? 3 to 12 months if the last regimen received is a platinum-based, or a treatment-free interval (TFI) of ? 3 to 12 months if the last regimen received is a non-platinum-based
Cohort B: Has received 3 to 5 additional prior lines for treating ROC (or 4-6 total prior lines counting the front line) and must have a PFI of ? 3 months if the last regimen received is a platinum-based, or a TFI of ? 3 months if the last regimen received is a non-platinum-based
Platinum-free interval (PFI) - patients must have progressed < 12 months after completion of their last platinum-based chemotherapy; the date (platinum free interval) should be calculated from the last administered dose of platinum therapy to documentation of progression
Have progressed during or after platinum-based chemotherapy for advanced disease.
Metastatic bladder cancer with disease progression on or after platinum-based chemotherapy
Have progressed after platinum-based chemotherapy (with or without maintenance therapy) AND have received one additional therapy which may include an immune checkpoint inhibitor or other anti-cancer therapy for advanced and/or metastatic disease OR is judged by the physician as ineligible for further standard second-line chemotherapy. Participants who have progressed after platinum-based chemotherapy and an immune checkpoint inhibitor (immunotherapy) e.g. pembrolizumab or nivolumab alone or in combination with other agents are eligible.
Maintenance therapy following platinum doublet-based chemotherapy is not considered as a separate regimen of therapy
Subjects with recurrent disease >6 months after platinum-containing adjuvant, neoadjuvant or definitive chemoradiation therapy given for locally advanced disease, who also subsequently progressed during or after a platinum doublet-based regimen given to treat the recurrence are eligible
Prior chemotherapy: Cohort 1) PR or CR to prior platinum-containing regimen for metastatic disease with disease progression > 8 weeks following the last dose of platinum; or Cohort 2) > 2 prior chemotherapy regimens for metastatic disease and no prior platinum for metastatic disease
Received ?2 prior platinum-based treatment regimens including platinum based regimen that must have been administered immediately prior to maintenance therapy in this trial.
Received no more than 1 non-platinum chemotherapy regimen. Prior hormonal therapy will not be counted as a non-platinum regimen.
Must have had at least a 6-month disease-free period following prior treatment with the penultimate platinum-based chemotherapy and achieved a response.
For the last chemotherapy course prior to study entry, patients must have received a platinum-based doublet chemotherapy regimen and have achieved a CR or PR (as defined by RECIST) and/or a GCIG CA-125 response.
Required drainage of ascites during the final 2 cycles of their last platinum-based regimen and/or during the period between the last dose of chemotherapy of that regimen and randomization to maintenance treatment in this study.
Radiographic progression after treatment with at least 2 cycles of a platinum-containing doublet
Patients with platinum resistant cancer
Documented relapse or disease progression during or after first-line platinum-based therapy (subjects refractory to initial platinum-based therapy are eligible).
Candidate for re-treatment with original platinum-based regimen as second-line therapy.
At least 3 but no more than 9 weeks between the administration of the last cycle of platinum-based chemotherapy and randomization.
The patient must have received an appropriate platinum-based chemotherapy in the first line setting.
If the patient has platinum-sensitive relapsed disease (first relapse > 6 months from end of initial platinum disease), the patient should have been re-treated with platinum for relapsed disease (or be intolerant or have refused such treatment).
The patient must have demonstrated disease progression following platinum-based chemotherapy.
Recurrent platinum-resistant disease, defined as disease progression within 6 months (182 days) of the last receipt of platinum-based chemotherapy
Participants must have received a first-line platinum-based chemotherapy regimen
Participants with platinum-resistant or platinum-sensitive disease (within 12 months) are eligible; platinum-resistant disease is defined as relapse within 6 months after the last dose of platinum-based chemotherapy; platinum-sensitive disease is defined as relapse greater than 6 months after the last dose of platinum-based chemotherapy; participants with platinum-sensitive disease who have experienced relapse within 6 to 12 months after the last dose of platinum-based chemotherapy are eligible; participants with primary platinum-refractory disease (defined as progression during or relapsed within 2 months of their initial platinum-based chemotherapy) are not eligible
Patients with primary platinum-refractory disease are ineligible; primary platinum-refractory disease is defined as relapse less than 2 months after initial platinum-based chemotherapy
Patients with platinum-sensitive disease with relapse greater than 12 months after the last dose of platinum-based chemotherapy are ineligible
Patients must have had one prior platinum-based chemotherapeutic regimen for management of primary disease containing carboplatin, cisplatin, or another organoplatinum compound; this initial treatment may have included intraperitoneal therapy, consolidation, biologic/targeted (non-cytotoxic) agents (e.g., bevacizumab) or extended therapy administered after surgical or non-surgical assessment
Patients must have platinum resistant cancer with a platinum free interval of < 6 months; progression after last platinum is based on investigator assessment
Patients cannot have primary platinum refractory cancer, i.e. documented cancer progression while receiving platinum or within one month of receipt of a platinum based regimen
Subjects must have recurrent or persistent platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal carcinoma with measureable disease (as defined by RECIST 1.1.) who have received at least one prior platinum-based therapy\r\n* Platinum-based therapy is defined as treatment with carboplatin, cisplatin or another organoplatinum compound\r\n* Platinum-resistant is defined as having had disease progression within 6 months or most recent platinum therapy, or having disease progression while receiving previous platinum-based chemotherapy\r\n* Histologic documentation of diagnosis of carcinoma is required and the following histologic subtypes are eligible: high grade serous, clear cell, endometrioid, carcinoma, adenocarcinoma, mixed (including above subtypes only)
Participants who are allergic to any platinum agent
Platinum-sensitive ovarian cancer defined by recurrence or progression of disease > 6 AND < 24 months after completion of the most recent platinum-based therapy.
Evidence of platinum-refractory ovarian cancer defined as recurrence or progression during the first 6 cycles of or < 6 months after the beginning of first-line platinum based chemotherapy.
Evidence of platinum-resistant ovarian cancer defined as recurrence or progression within 6 months after completing the most recent platinum-based therapy.
Must have recurrence or progression after platinum-based first-line chemotherapy or chemoradiation therapy for the treatment of limited or extensive disease stage SCLC
Histologically or cytologically confirmed recurrent, metastatic or unresectable HNSCC of the oral cavity, oropharynx, hypopharynx, and larynx that that has either progressed during or after platinum-based chemotherapy administered for metastatic disease or has recurred during or within 6 months after the completion of platinum-based neoadjuvant or adjuvant therapy
Received at least 1 platinum-based chemotherapy regimen. Note: Subjects with EGFR mutations or ALK translocations are required to have received prior therapy with appropriate TKI; prior platinum-based chemotherapy is not required for this specific patient population
Prior chemotherapy regimens must include a platinum and/or a fluoropyrimidine component and must not include a taxane or antiangiogenic agent.
Disease must have been persistent or have recurred within 6 months (182 days) of a prior platinum therapy; disease may not have progressed during prior platinum therapy (i.e. refractory)\r\n* Evidence of progression and the timing of progression or reoccurrence will be new measurable disease, RECIST defined progression, or first doubling of the CA-125 nadir (however, that will need a confirmatory CA-125 to be done at least 2 weeks or later and the patient will need to have “detectable disease”\r\n* While the disease must have been persistent or progressive within 6 months of a prior platinum therapy, the patient may be enrolled and begin treatment up to 12 months (365 days) after the last dose of platinum-based therapy
Subjects must have recurrent or persistent platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal carcinoma with measureable disease (as defined by RECIST 1.1.) after first or second line platinum-based chemotherapy, for which treatment with PLD is indicated. Platinum-based therapy is defined as treatment with carboplatin, cisplatin or another organoplatinum compound. Platinum-resistant is defined as having a platinum-free interval (PFI) of < 12 months after first- or second-line platinum-based chemotherapy, or having disease progression while receiving second-line platinum-based chemotherapy. Subjects are allowed to have received, but are not required to have received:
Documented radiographic disease progression < 12 months after the last dose of first- or second-line platinum-based chemotherapy.
Subjects with platinum-refractory disease, defined as disease progression while receiving first line platinum-based therapy.
Participants must have received at least one prior platinum-based regimen for advanced cholangiocarcinoma and had progressive disease or become intolerable to the regimen
Platinum-resistant disease (PFI: 1-6 months after last platinum-containing chemotherapy).
No more than 2 prior lines of cytotoxic therapy, which should have included pemetrexed and a platinum
Progression on or after prior first-line therapy containing any platinum/fluoropyrimidine doublet
Disease progression or recurrence after both a platinum-based chemotherapy regimen and at least 1 additional regimen for treatment of NSCLC
For platinum sensitive cohort\r\n* Cancer that has not progressed within 6 months of the last receipt of platinum-based chemotherapy\r\n* No limit on the number of platinum-based lines\r\n* No more than one prior non-platinum based line of therapy in the recurrent setting
For platinum-resistant or -refractory cohort\r\n* Disease that has progressed within 6 months of the last receipt of platinum-based chemotherapy\r\n* No more than 1 prior line of therapy in the platinum-resistant/-refractory setting\r\n* No limit on number of prior lines received in the platinum-sensitive setting prior to development of platinum-resistance (defined as disease progression within 6 months of platinum-based chemotherapy)
Received one or more lines of chemotherapy, which must include prior treatment with a platinum agent and must not be amenable to potentially curative radiotherapy or surgery
Patients must have had one prior platinum-based chemotherapeutic regimen for management of primary disease; platinum sensitive and resistant patients are eligible
Histologically confirmed estrogen receptor positive (greater than 10%) recurrent ovarian, fallopian tube or primary peritoneal carcinoma in post-menopausal women; note: pure clear cell and pure mucinous carcinomas are ineligible; both platinum sensitive, platinum resistant and platinum refractory disease are eligible; no limitations in the number of prior regimens
Patients must have previously received, not tolerated, or been judged clinically unsuitable for platinum-containing therapy
All patients with ovarian, fallopian tube or primary peritoneal cancer and ovarian carcinosarcoma must have recurrent disease, and only one prior line of chemotherapy that must have been platinum-based chemotherapy for the management of primary disease; this initial platinum-based treatment may have included intraperitoneal therapy, consolidation/maintenance and/or biologic/targeted agents (e.g., bevacizumab, poly adenosine diphosphate [ADP] ribose polymerase [PARP] inhibitor) as part of first-line treatment
Patients with endometrial cancer or endometrial carcinosarcoma may either be chemotherapy naive or have had one prior line of chemotherapy that must have been a platinum-based chemotherapy regimen in the adjuvant or advanced/recurrent setting; the initial platinum-based treatment may have included consolidation/maintenance and/or biologic/targeted agents as part of first-line treatment; patients entering the trial chemotherapy naive must have stage IVB or recurrent disease and have disease that is not amenable to curative intent
Progression or recurrence of urothelial cancer following a first-line platinum-containing regimen (e.g cisplatin, carboplatin) for metastatic or inoperable locally advanced disease; or adjuvant platinum-based therapy following cystectomy for localized muscle-invasive urothelial cancer with recurrence/progression <=12 months following completion of therapy; or neoadjuvant platinum-containing therapy prior to cystectomy for localized muscle-invasive urothelial cancer with recurrence <=12 months following completion of therapy
Tumor progression or recurrence within 6 months of the last dose of any number of platinum-based and cetuximab therapy lines in the adjuvant, primary, recurrent, or metastatic setting; must be resistant (not responding) to both platinum and cetuximab
Failure of prior platinum therapy
Tumor progression or recurrence during or after treatment with only 1 systemic palliative regimen for recurrent or metastatic disease that must have contained a platinum agent.
Once subjects on the platinum-based doublet chemotherapy arm are determined to have objective radiological progression according to RECIST 1.1 by the investigator and confirmed by independent central imaging review.
At least 14 days since last dose of platinum-based doublet chemotherapy
Patients must have received at least 2 cycles of platinum-based chemotherapy concurrent with radiation therapy.
A regimen was defined as participants receiving at least two cycles of a platinum-containing regimen. Participants who had received one cycle of a platinum-containing regimen but discontinued due to Grade 4 hematologic toxicity or Grade 3 or 4 non-hematologic toxicity could also be eligible.
Disease progression or recurrence after both a platinum-based chemotherapy and at least 1 additional regimen for treatment of NSCLC
Documented disease progression after a platinum based chemotherapy in patients for whom administration of taxanes and anthracyclines is not planned. Progression must fulfill one of the following criteria:
Progression has occurred within 30 days of platinum based chemotherapy consisting of minimum of two cycles of cisplatin-based (?60 mg/m2/cycle) or carboplatin-based (?300 mg/m2/cycle, or area under the time-concentration curve ?4) chemotherapy.
Patients who have failed previous intraperitoneal platinum therapy will be ineligible (“failed” is having disease recurrence =< 3 months)
Ovarian cancer patients with both platinum-sensitive and platinum-resistant disease are eligible; ovarian cancer patients with platinum refractory disease (failure to achieve a complete response to first line platinum therapy) are ineligible
Patients with advanced breast cancer who have received platinum therapy (e.g. carboplatin or cisplatin) and/or gemcitabine therapy for metastatic disease are excluded (platinum-based therapy and/or gemcitabine in the adjuvant or neoadjuvant setting is allowed)
Patients must have had one prior platinum-based chemotherapeutic regimen for management of primary disease containing carboplatin, cisplatin or another organoplatinum compound; patients are also eligible if they received curative intent platinum-based therapy and progressed within a year of therapy
Patients must have received at least one platinum based chemotherapy, and not more than two prior chemotherapy agents and three prior therapies if EGFR or ALK TKI received for EGFR mutation or ALK translocation positive stage IIIB/IV disease\r\n* Patients who received adjuvant or neoadjuvant platinum-doublet chemotherapy (after surgery and/or radiation therapy) and developed recurrent or metastatic disease within 6 months of completing therapy are eligible and the adjuvant or neoadjuvant chemotherapy will count as a line of therapy as above\r\n* Subjects with recurrent disease > 6 months after adjuvant or neoadjuvant platinum-based chemotherapy, who also subsequently progressed during or after a platinum-doublet regimen given to treat the recurrences, are eligible and do not count as another line of therapy for advanced disease\r\n* Subjects who received pemetrexed, bevacizumab, or erlotinib as maintenance therapy (nonprogressors with platinum-based doublet chemotherapy) and subsequently progressed after maintenance therapy are eligible and do not count as a line of therapy; however, subjects who received a tyrosine kinase inhibitor after failure of a prior platinum-based therapy, that tyrosine kinase inhibitor therapy would count as an additional line of therapy
Completion of induction chemotherapy with a minimum of 4 and no more than 6 cycles of a platinum agent and etoposide within 8 weeks of trial initiation.
At least one prior line of systemic therapy including platinum and pemetrexed
PART B: Patients must have received prior platinum-based chemotherapy but may have received any number of other lines of prior therapy
Patients who have received at least 2 previous lines of platinum containing therapy prior to randomisation For the penultimate chemotherapy course prior to enrolment on the study: • Patient defined as platinum sensitive after this treatment; defined as disease progression greater than 6 months after completion of their last dose of platinum chemotherapy For the last chemotherapy course immediately prior to randomisation on the study:
Patient must have received a platinum based chemotherapy regimen (e.g. carboplatin or cisplatin) and have received at least 4 cycles of treatment
Maintenance treatment is allowed at the end of the penultimate platinum regimen, including bevacizumab
Patients who have completed first line platinum (e.g. carboplatin or cisplatin), containing therapy (intravenous or intraperitoneal) prior to randomisation:
Known standard therapy for the patient’s disease that is potentially curative or definitely capable of extending life expectancy; note: patients with recurrent platinum-sensitive ovarian, primary peritoneal or fallopian tube will be allowed, if the investigator believes the study treatment is a better alternative to initiation platinum-based chemotherapy, such as patients with a prior platinum allergy or low volume disease for whom platinum-based therapy is deferred until a later date
Must have had prior platinum or platinum based therapy.
Platinum resistant or refractory disease within 6 months of completing or while receiving a platinum and taxane containing regimen
Disease recurrence or progression during/after one prior platinum doublet-based chemotherapy regimen for advanced or metastatic disease
Have been treated one time with a platinum-based chemotherapy and your disease has come back at least six months after you completed treatment
Patients may be platinum-sensitive or resistant; group A (monotherapy cohort); participants may have received up to 3 prior cytotoxic chemotherapies, i.e., second or third line; there is no limit to the number of lines of prior biologic or hormonal therapies they may have had; patients may be platinum-sensitive or resistant or refractory
Participants must have platinum-resistant disease, (defined as progression within < 6 months from completion of a minimum of 4 platinum therapy cycles; the date should be calculated from the last administered dose of platinum therapy)
Patients whose disease was refractory to their previous platinum treatment; refractory disease is defined as those patients who progressed during the preceding platinum treatment
Patients who will receive CXRT with platinum/taxane-based chemotherapy and with a total radiation dose of >or = 50 Gy, per treating physician's assessment
At least one prior line of platinum-based chemotherapy or patient must have refused cytotoxic chemotherapy; progressive disease must be documented prior to study entry
Must have a diagnosis of recurrent epithelial ovarian, primary peritoneal or fallopian tube carcinoma with refractory or platinum resistant disease and/or have received ? 2 lines of chemotherapy
Patients with platinum-sensitive or platinum-resistant disease defined by recurrence or progression of disease > 6 months or =< than 6 months after completion of frontline platinum based chemotherapy
For Cohorts A and B, documented tumor progression (based on radiological imaging) after receiving at least one prior approved platinum-based chemotherapy regimen for advanced stage/metastatic NSCLC. An alternate chemotherapeutic agent/regimen is an acceptable substitute in the event that the subject was intolerant to, or ineligible to receive platinum based chemotherapy. Subjects enrolled in Cohort B cannot have more than 3 prior systemic treatments for advanced stage/metastatic NSCLC (neoadjuvant and adjuvant therapies are not counted in number of prior regimens and maintenance therapy is not counted as a separate regimen). Subjects in Cohort C will be required to have not received prior systemic anti-cancer therapies for metastatic disease (i.e., dabrafenib/trametinib will be 1st line treatment for metastatic disease);
Patient has received at least one prior platinum-containing (cisplatin or carboplatin) regimen
EXPANSION COHORT ONLY: Previously treated with at least one and not more than 3 lines of systemic chemotherapy including at least one of the following: a platinum agent, a taxane, or gemcitabine
Subject is platinum sensitive (progression free interval >= 6 months prior to recent recurrence) or platinum resistant (progression free interval < 6 months prior to recent recurrence)
Progressive or recurrent disease occurring\r\n* During or after treatment with a platinum containing regimen (cisplatin or carboplatin or novel platinum) in either in the metastatic or perioperative setting\r\n* In first-line patients defined as platinum ineligible based on renal impairment (creatinine clearance calculated by Cockcroft-Gault method < 60 ml/min), grade 2 hearing loss and/or Eastern Cooperative Oncology Group (ECOG) status of 2; these patients will be chemotherapy naive or have received platinum based therapy in the adjuvant or neoadjuvant setting more than 12 months prior to study entry
Subjects with UC (including renal pelvis, ureter, bladder, urethra) after prior platinum-based therapy, or
Subjects must have received at least 1 prior platinum-based line of chemotherapy for ovarian cancer. Note: There is no limit on the number of lines of chemotherapy;
Subjects must be partially-platinum-sensitive (defined as progression 6 to 12 months after the end of the last platinum-based chemotherapy) or platinum sensitive (defined as progression > 12 months after the end of the last platinum-based chemotherapy);
Subjects who have platinum-resistant or refractory disease defined as progression during or within 6 months of the last platinum-based chemotherapy;
PRIOR THERAPY PHASE II:\r\n* Prior chemotherapy must have included a first-line platinum-based regimen with or without intravenous consolidation chemotherapy\r\n* Prior hormonal-based therapy for ovarian, primary peritoneal serous, or fallopian tube cancer is acceptable\r\n* Patients may not have previously received a PARP-inhibitor; prior treatment with BSI-201 is allowed\r\n* Patients may not have had a prior anti-angiogenic agent in the recurrent setting\r\n* Patients may have received up to 1 non-platinum-based line of therapy in the recurrent setting\r\n* Patients may have received an unlimited number of platinum-based therapies in the recurrent setting\r\n* Patients should have platinum-sensitive disease, where platinum-sensitive disease is defined as having had a > 6 month interval since last receiving platinum therapy prior to disease recurrence; patients must have had a prior response while on the platinum-containing regimen and cannot have experienced disease progression while receiving platinum
Prior systemic regimens must include at least 2 cycles of a platinum-based therapy and may include platinum therapy used as a radiosensitizer. Maintenance chemotherapy is allowed.
Subjects initially treated with a platinum regimen for Stage IIIB disease who later develop metastatic disease and are re-treated with a platinum regimen are allowed.
Stage IV locally advanced or metastatic urothelial carcinoma with disease progression during or following platinum-containing chemotherapy or had disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.
Subjects are eligible after first line platinum based chemotherapy if their disease has relapsed and they have primary mediastinal non seminomatous germ cell tumor (PMNSGCT) or late relapse (> 2 years) not amenable to surgical resection
Expanded Safety Cohort participants must have confirmed metastatic lung cancer and progressed after receiving prior platinum-containing chemotherapy.
Patients must be platinum resistant defined as progressive disease while receiving platinum therapy or within 6 months of completing first line platinum therapy or patients who have progressive disease after two lines of platinum-based treatment
Recurrent or progressive disease after one prior platinum-based non-pemetrexed chemotherapy treatment for advanced disease with or without maintenance
Recurrent or refractory disease after receiving at least one prior standard/approved platinum-containing chemotherapy regimen, or where standard therapy is refused. Part 2 only: Subjects must have recurrent disease after receiving a maximum of two prior chemotherapy regimens including at least one platinum containing regimen.
Metastatic ovarian epithelial cancer that are platinum-resistant, and has no better option available in the investigator's opinion
Participants must have progressed on one prior line of platinum-based chemotherapy in the advanced or metastatic setting.
Participants who received prior therapy with paclitaxel as a part of the platinum-based doublet front-line regimen without PD on therapy.
Participants who, after the front-line, platinum-based, non-docetaxel containing chemotherapy, have been treated with 1 line of nivolumab or other immune-checkpoint inhibitors but progressed on or after the therapy.
Patients must have platinum-refractory disease defined as disease progression within 12 months platinum-based chemoradiation with curative intent or any disease progression on platinum-based chemotherapy in the absence of radiation.
Prior therapy: patients must have had one prior platinum-based chemotherapeutic regimen for management of primary disease containing carboplatin, cisplatin, or another organo-platinum compound; this initial treatment may have included intraperitoneal therapy, consolidation, non-cytotoxic agents (including anti-angiogenesis agents) or extended therapy (i.e. maintenance therapy) administered after surgical or non-surgical assessment; maintenance therapy should not be longer than 18 months duration
Patients who have received only one prior cytotoxic regimen (platinum based regimen for management of primary disease), must have a platinum-free interval of 6 to 12 months; patients who have progressed during platinum-based therapy or have persistent disease after a platinum-based therapy are excluded
Patients who have progressed during initial platinum-based therapy in the upfront setting, who have persistent disease after this initial platinum-based therapy, or who have recurrence less than 6 months from adjuvant chemotherapy are excluded
Histologically confirmed, adenocarcinoma of the lung, after failure of first line platinum-based chemotherapy.
Treatment naive OR one prior standard chemotherapy that is platinum-based
NSCLC (Non-small-cell lung cancer): Patients with NSCLC and known KRAS status after platinum based chemotherapy.
Maintenance therapy for patients after completion of four cycles of dual-agent platinum-based chemotherapy
Must have received one or two prior lines of systemic chemotherapy for advanced or metastatic disease, one of which must be a platinum-doublet therapy.
Eligibility for platinum-based chemotherapy
Patients must have received 1 prior platinum containing doublet regardless of mutation status
Patients receiving chemotherapy (e.g., docetaxel, cabazitaxel, taxane, or platinum as single agents or in combination) as their cancer treatment
Patients with recurrent or metastatic disease resistant to platinum-based chemotherapy (defined as progression while on platinum-based chemotherapy given in the recurrent/metastatic setting). Pretreatment with cetuximab is allowed
Patients must have received prior platinum containing treatment.
Patients must be resistant to platinum-based chemotherapy, or be ineligible (due to medical comorbidities) or intolerant to platinum-based therapy per medical history
Prior therapy with an anti-HER2 agent and/or platinum-based chemotherapeutic agent
After concomitant platinum-based CRT, no evidence of disease (NED) on clinical and radiographic examinations
Recurrent or progressive disease on or after initial platinum-based chemotherapy
Previously received at least 3, but no more than 6, lines of therapy including at least 1 course of platinum-based therapy
Recurrent platinum-sensitive disease, defined as disease progression ?6 months after completing a minimum of 4 cycles of a platinum-containing regimen
Prior treatment with paclitaxel and carboplatin for recurrent platinum-sensitive ovarian cancer
Disease that has progressed or relapsed during or within 6 months after the most recent treatment with a platinum-containing chemotherapy regimen
Progression or relapse from prior platinum-based chemotherapy must be documented radiographically by RECISTv1.1 criteria For ovarian cancer dose expansion cohorts only:
Not more than two prior chemotherapy regimens for the treatment of platinum-resistant ovarian cancer Participants with Pancreatic Cancer:
Completed 1 line of chemotherapy treatment with a platinum-containing regimen in the advanced setting
Subjects with serous ovarian/fallopian tube/primary peritoneal, granulosa cell tumors or clear cell tumors considered platinum refractory/resistant, defined as having at least one prior platinum-based chemotherapeutic regimen with a subsequent platinum-free interval of < 12 months, having progression during platinum-based therapy, or having persistent disease after a platinum-based therapy, are eligible. Intolerant subjects, defined as unable to receive further platinum due to toxicity, are eligible.
Has received at least 2 previous courses of platinum-containing therapy, and has disease that was considered platinum sensitive following the penultimate (next to last) platinum course (more than 6 month period between penultimate platinum regimen and progression of disease)
Has responded to last the platinum regimen, remains in response and is enrolled on study within 8 weeks of completion of the last platinum regimen
Platinum-refractory germ-cell tumors.
platinum-resistant cancer, defined as disease that responded to a platinum-containing chemotherapy regimen, but demonstrated recurrence within six months following the completion of that platinum-containing regimen, OR
platinum-refractory cancer, defined as disease failed to achieve at least a partial response to a platinum-containing regimen (i.e., stable disease or actual disease progression), AND
Platinum resistant/refractory disease, defined as disease progression/relapse within 6 months following the last administered dose of platinum therapy (resistant), or lack of response or disease progression while receiving the most recent platinum based therapy (refractory), respectively
Participants must have recurrent or refractory disease after receiving at least one prior platinum-containing chemotherapy regimen, or standard therapy is refused or not suitable. For participants in Canada: participants should also not be suitable for treatment with topotecan hydrochloride
Subject has experienced disease progression or unacceptable toxicity/intolerance after receiving at least 1 systemic platinum-containing regimen;
Primary refractory disease (progressive disease on initial platinum based chemotherapy) or chemotherapy-resistant disease (disease progression within 90 days of completion of initial chemotherapy)
History of or suspected allergy to nab-paclitaxel, carboplatin and human albumin or any other platinum-based therapy.
Previously treated with one platinum-based chemotherapy
Prior history of hypersensitivity to taxane or platinum therapy; if either agent was previously administered, the patient must have tolerated it well and have recovered from any adverse events
Patients whose ovarian cancer recurs/progresses within 0-6 months following platinum-based chemotherapy have platinum resistant disease; such patients are eligible for this trial
Patients with documented disease recurrence/progression within 6-12 months of completing platinum-based therapy, are considered to have ‘borderline' platinum sensitivity; these patients are eligible for this trial if agreed by the patient and the treating physician
Patients who relapse more than 12 months after completion of platinum-based treatment are considered ‘platinum sensitive’ and will not be eligible for this trial
Eligible patients are those with documented disease recurrence/progression within 0-12 months of completing platinum-based chemotherapy
Prior chemotherapy that included a platinum agent
For ovarian cancer participants only, platinum-based chemotherapy within 6 months prior to Day 1.
For ovarian cancer participants only, platinum treatment with more than two platinum-based chemotherapy regiments or more than four anti-cancer regimens, overall, for the treatment of ovarian cancer.
Patients must have received one of the regimens listed below for their platinum sensitive disease; the number of treatment cycles should not have exceeded 8 cycles of 1 regimen in the recurrent setting; the most recent dose of the regimen must have been given within 3 to 8 weeks prior to the first dose of study drug; there is a required 3 week washout from the last dose of chemotherapy; if greater than 8 weeks have passed since the last chemotherapy dose, patients may be eligible with documented approval of the Principal Investigator\r\n* Platinum (carboplatin or cisplatin) and taxane (paclitaxel or docetaxel)\r\n* Carboplatin and gemcitabine\r\n* Carboplatin and liposomal doxorubicin\r\n* Any other carboplatin doublet (including carboplatin and pralatrexate) with documented approval of the Principal Investigator
Subjects must have platinum resistant disease (i.e., which is defined as disease progression in less than 6 months after receiving a minimum of 4 cycles of a platinum containing regimen).
Received a minimum of one course of treatment that included at least one platinum-based chemotherapy doublet for metastatic or locally recurrent disease.
At least 1 prior regimen must have contained a platinum salt
For Part 3, subject has ovarian cancer that was previously treated with platinum based chemotherapy resulting in progression free survival for < 6 months from the completion of treatment.
Progression during or after platinum-based therapy for recurrent or metastatic ESCC, or recurrence within 6 months of platinum-based chemotherapy or chemoradiotherapy for localized disease.
Prior treatment with crizotinib and progression according to RECIST v1.1 criteria with the last dose of crizotinib within 60 days from enrolment; patients can either be chemotherapy-naïve or have received at least one line of platinum-based chemotherapy
Progression during or after treatment with a regimen that includes a platinum salt (e.g., carboplatin or cisplatin) OR
5. Patients with advanced, recurrent or metastatic endometrial cancer who have received one chemotherapeutic regimen with platinum and taxane (either as adjuvant or as first line treatment) and who have progressed.
Histologically confirmed diagnosis of epithelial ovarian, fallopian tube or primary peritoneal cancer (measurable or evaluable, nonmeasurable disease) that is platinum-resistant or refractory. In the judgment of the Investigator, a patient who is platinum-sensitive but would not benefit from further platinum treatment is also eligible.
Must have had ? 1 prior platinum-based chemotherapeutic regimen containing carboplatin, cisplatin or another organoplatinum compound for management of primary disease. This initial treatment may have included intraperitoneal (IP) therapy, consolidation, non-cytotoxic agents or extended therapy administered after surgical or non-surgical assessment.
Patients must have had one prior platinum-based chemotherapy regimen for management of primary disease
Patients who have received only one prior cytotoxic regimen (platinum-based regimen for management of primary disease), must have a platinum-free interval of less than 12 months, or have progressed during platinum-based therapy, or have persistent disease after a platinum-based therapy
Patients must have completed front-line, platinum-based chemotherapy with CR, PR, or NED and have first study treatment dose within 12 weeks of the first day of the last cycle of chemotherapy:
A platinum-based regimen must have consisted of a minimum of 6 and a maximum of 9 treatment cycles. Patients who discontinued platinum-based therapy early as a result of non hematologic toxicity specifically related to the platinum regimen (ie, neurotoxicity or hypersensitivity) are eligible if they have received a minimum of 4 cycles of the platinum regimen.
IV, intraperitoneal, or neoadjuvant platinum-based chemotherapy is allowed; for weekly therapy, 3 weeks is considered 1 cycle. Interval debulking is allowed.
Patients must have received, prior to enrollment, a minimum of 3 cycles of bevacizumab in combination with the last 3 cycles of platinum-based chemotherapy. Patients who undergo interval debulking surgery are eligible if they have received only 2 cycles of bevacizumab in combination with the last 3 cycles of platinum-based chemotherapy.
Platinum-treated patient that progressed while on or within less than 8 weeks from the last day of platinum administration
Tumor progression or recurrence within 6 months of last dose of platinum therapy that was used to treat metastatic, persistent or recurrent cervical cancer
Up to 6 patients with histological or cytological documentation of advanced ovarian, fallopian tube, or primary peritoneal carcinoma with a history of progression or recurrence following at least one prior platinum and one taxane based chemotherapy
Squamous Cell Carcinoma of the Cervix (SqCC) All patient with Squamous Cell Carcinomas should have a documented history of progression or recurrence following at least one prior platinum based chemotherapy or chemotherapy/radiation containing regimen
Progressive disease on or after first-line platinum-based chemotherapy regimen for R/M SCCHN (maximum of 6 cycles)
No more than one platinum-based chemotherapy regimen for R/M SCCHN is allowed
Prior platinum-based treatment as definitive chemo/radiotherapy for locally advanced disease is allowed if completed/terminated >/= 6 months before the platinum-based regimen for R/M SCCHN
For Stage 2: Participants with non-mucinous, platinum-resistant ovarian cancer with documented radiographic progression or relapse according to RECIST within 6 months of receiving platinum-based chemotherapy
Prior treatment with at least one platinum-based line of treatment (for stage IIIb/IV) and no more than one additional line of chemotherapy treatment; the last dose of chemotherapy must have been administered >/= 21 days prior to Day 1
Documented progression of disease (locally recurrent or metastatic) per investigator assessment following first-line treatment with 4-6 cycles of Bevacizumab plus a platinum doublet-containing chemotherapy regimen and a minimum of 2 cycles of Bevacizumab (monotherapy) maintenance treatment prior to first progression of disease
Any other than one previous platinum based systemic regimen given for R/M disease
Participants who are allergic to platinum agent
must have had disease progression after only one prior chemotherapy and that regimen but must have included one platinum drug
Patients must have experienced progressive disease following at least one platinum-based chemotherapy regimen in the setting of advanced disease or have progressed within 6 months of receiving chemotherapy as part of loco-regional therapy
Refractory to platinum-based therapy (defined as disease progression within 6 months of last dose of platinum chemotherapy)
For the dose expansion cohort, patients with ovarian, fallopian tube or primary peritoneal cancer must have platinum resistant disease defined as progression within 6 months after last platinum regimen; platinum refractory disease is allowed
Have completed neurotoxic chemotherapy, i.e. taxanes (paclitaxel, docetaxel) and platinum (carboplatin) at least 3 months prior to enrollment
PATIENTS: Platinum-resistant ovarian cancer or recurrent ovarian cancer as described below\r\n* Platinum-resistant disease is defined as:\r\n** Recurrent disease < 6 months from end of platinum-based chemotherapy or\r\n** Progression of disease while on first line platinum-based chemotherapy or\r\n** Initially platinum-sensitive disease that becomes platinum-resistant during treatment\r\n* Recurrent ovarian cancer with any one significant clinical event following completion of chemotherapy:\r\n** Ascites\r\n** Bowel obstruction\r\n** Pleural effusion
PATIENTS: Platinum-sensitive recurrent ovarian cancer without a significant clinical event
Recurrent or metastatic disease that has been treated with at least one platinum-containing regimen and lacking a curative treatment option.
There is no upper limit of prior therapies but patients must have had one prior chemotherapeutic regimen for management of endometrial carcinoma; initial treatment may include chemotherapy, chemotherapy and radiation therapy, and/or consolidation/maintenance therapy; any platinum based chemotherapy (single agent platinum or any platinum doublet) administered in conjunction with primary radiation as a radio-sensitizer WILL be counted as a systemic chemotherapy regimen; furthermore, patients who have only received chemotherapy in the adjuvant setting will be eligible for the study
Have ED-SCLC and have received a prior platinum-based regimen
Participants in Cohort 1 must have had an objective response to prior platinum-based therapy with subsequent progression ?90 days after the last dose of platinum
Participants in Cohort 2 must have either not had an objective response to prior platinum based therapy or had progression <90 days after the last dose of platinum
Patients must not have received any prior taxane or platinum based chemotherapy
Known allergies or intolerance to cisplatin and similar platinum-containing compounds
Have received one or more of the following chemotherapy (CTX) drugs: taxanes or platinum compounds
Has received a platinum compound and/or a taxane
Primary platinum refractory
At least one prior chemotherapeutic regimen for advanced metastatic/recurrent disease, of which at least one regimen included a platinum agent (unless contraindicated)
Patient must have completed 4-6 cycles of platinum-based chemotherapy (+/- thoracic radiotherapy)
Known allergies or intolerance to cisplatin and similar platinum-containing compounds
Patients who are planned to receive definitive or adjuvant radiotherapy with concurrent platinum-based chemotherapy
Patients with epithelial ovarian, fallopian tube, or primary peritoneal cancer must also meet the following criteria: a. Must be either platinum-resistant or platinum-refractory according to the following definitions:(1)Platinum-resistant: a response to platinum therapy followed by progression within 6 months after completing therapy (2)Platinum-refractory: best response of stable disease or progression during platinum therapy; b. Must have had prior systemic treatment with a taxane; c. Must have received no more than 4 prior systemic cytotoxic regimens
Patient must have suspected platinum-resistant disease (disease progression =< 6 months of platinum therapy)
Epithelial ovarian cancer, including fallopian tube cancer or primary peritoneal cancer, of high-grade serous histology, with platinum refractory or resistant disease after prior treatment with at least one platinum-based chemotherapeutic regimen. In Part B (dose expansion), subjects may have received no more than 3 lines of systemic cytotoxic chemotherapy.
Metastatic or advanced endometrial carcinoma previously treated with at least 1 platinum-based chemotherapeutic regimen.
Suitable to receive a platinum-based chemotherapy regimen as 1st line treatment.
Epithelial ovarian cancer which is contained within the abdomen, but may include pleural effusion if that is the limit of non-peritoneal cavity disease. If subject has recurrent epithelial ovarian cancer, the disease must be platinum sensitive (recurrence >6 months from prior chemotherapy regimen that included a platinum agent and cytoreductive surgery)
Platinum-sensitive SCLC after having received up to two prior lines of anticancer therapy, including at least one prior line of a platinum (monotherapy or platinum containing chemotherapy regimen). Patients are eligible only if they had a response (partial or complete) to their most recent platinum and their disease progressed greater than 60 days after completing their most recent platinum. Patients may have received another non-platinum containing regimen, such as topetecan, immunotherapy, or an investigational agent, as their most recent line of therapy, so long as they are deemed platinum sensitive per the above definition.
Patients can either be chemotherapy-naive or have received at least one line of platinum-based chemotherapy for locally advanced or metastatic disease; acute effects of therapy must have resolved to baseline severity or to CTCAE grade =< 1 except for AEs that in the investigator’s judgment do not constitute a safety risk for the patient
Have pathologically proven ovarian cancer or cancer of mullerian origin that requires first-line treatment with a taxane + platinum based chemotherapy regimen
Has received systemic chemotherapy for ovarian cancer or cancer of mullerian origin other than first-line treatment with a taxane + platinum based chemotherapy regimen
Scheduled to receive front-line platinum-based chemotherapy with carboplatin or cisplatin plus etoposide
Disease must have progressed after treatment with a platinum-containing regimen and should be defined as one of the following: i. disease progression or recurrence between 3 to 6 months of prior curatively intended multimodal therapy (which includes platinum therapy) for locoregionally advanced SCCHN. ii. disease progression or recurrence after prior platinum therapy in the recurrent or metastatic setting Note: This criterion is only applicable for subjects who have not had treatment in the recurrent/metastatic setting
If the participant has received prior therapy with platinum, the time to the first treatment of study drug from the last platinum exposure is >28 days.
If the participant has received prior therapy with platinum, the time to the first treatment of study drug from the last platinum exposure is >28 days.
Received debulking surgery and preoperative and/or postoperative platinum-based frontline chemotherapy (intravenous and/or intraperitoneal) for the treatment of EOC/FTC/PPC.
Documented platinum-resistant or platinum-refractory disease. Platinum-resistant disease is defined as progression within < 6 months from completion of a minimum of 4 platinum frontline therapy cycles in the pre or postoperative setting (the date should be calculated from the last administered dose of platinum agent). Platinum-refractory is defined as disease that has recurred/progressed while receiving platinum-based frontline therapy.
More than 2 prior treatment regimens for the platinum-resistant/refractory relapsed EOC, FTC, or PTC, defined as investigational, chemotherapy, hormonal, biologic, or targeted therapy.
PD during or following at least 1 prior treatment. Participants should have received a prior platinum-based 2-drug regimen for locally advanced, unresectable/ inoperable or metastatic NSCLC or disease recurrence within 6 months of treatment with a platinum-based adjuvant/neoadjuvant regimen or combined modality (example, chemoradiation) regimen with curative intent.
Tumor progression or recurrence within 6 months of the last dose of platinum-based therapy in the adjuvant (that is, with radiation after surgery), primary (that is, with radiation), recurrent, or metastatic setting.
Considered to be eligible to receive platinum-based chemotherapy, in the investigator's judgment
Part B: must have received at least 1 prior therapy containing platinum-based chemotherapy for advanced/metastatic NSCLC
Patients who have had prior platinum-based therapy who have > grade 1 neurotoxicity or ototoxicity at the time of enrollment will not be permitted on study
Progression after platinum-based chemotherapy