More than one line of prior chemotherapy for metastatic or locally advanced disease with the following exception:\r\n* Prior neoadjuvant/adjuvant chemotherapy will not count as line of therapy if completed greater than 12 months prior to initiation of chemotherapy regimen for metastatic or unresectable disease
The patient must have experienced disease progression during or within 4 months after the last dose of chemotherapy for metastatic disease, during or within 6 months after the last dose of adjuvant chemotherapy, or have been intolerant of previous chemotherapy
Patients must have had at least one prior regimen of systemic chemotherapy for metastatic or locally advanced, unresectable disease; patients must have progressed following the most recent therapy; prior treatment with irinotecan is allowed; for patients that received adjuvant chemotherapy: prior treatment for metastatic disease is not required for patient who experienced disease recurrence during or within 6 months of completion of adjuvant chemotherapy; if the patient received one line of adjuvant treatment and had disease recurrence after 6 months of completing chemotherapy, patients will only be eligible after failing one additional line of chemotherapy used to treat the metastatic or locally advanced, unresectable disease; patients who have received >= 3 lines of systemic chemotherapy for metastatic or locally advanced, unresectable disease are not eligible
Patients may have received only one prior chemotherapy regimen for metastatic disease provided treatment was completed >= 3 weeks prior to randomization
Progression on at least one prior systemic chemotherapy for advanced, unresectable or metastatic disease; prior adjuvant or neoadjuvant therapy is not included as prior systemic chemotherapy unless treatment occurred within the 6 months prior to study enrollment
Prior chemotherapy:\r\n* History of prior therapy with trastuzumab and a taxane, separately or in combination, is required\r\n* Patients must have either received one line of prior therapy for metastatic breast cancer, or have developed a disease recurrence during or within 6 months after completing adjuvant therapy\r\n* No prior treatment with T-DM1 is allowed\r\n* Last dose of chemotherapy must be at least 21 days prior to registration
Any prior chemotherapy for castration-resistant disease is not allowed. Previous and/or concurrent treatment with other anti-cancer treatments is permitted. Patients are allowed to be treated with chemotherapy during the duration of the trial. Patients who have received chemotherapy as part of initial androgen deprivation therapy for metastatic castration sensitive disease are eligible.
Biopsy-proven metastatic pancreatic adenocarcinoma with documented radiographic disease progression on or after one or more systemic therapies. Chemotherapy given as part of prior chemoradiation in the setting of non-metastatic pancreatic cancer does not count as a line of therapy. Chemotherapy given for at least 4 months as adjuvant after complete response is considered as a first line therapy.
Participant has received more than one prior chemotherapy regimen for metastatic disease.
Patients may have received adjuvant chemotherapy and up to two prior chemotherapy for metastatic or locally recurrent disease; no prior nab-paclitaxel or mifepristone therapy for metastatic disease will be allowed
Before the first dose of study drug: a) Has received prior systemic cytotoxic chemotherapy for metastatic disease; b) Has received other targeted or biological antineoplastic therapy (e.g., erlotinib, crizotinib, cetuximab) for metastatic disease; c) Has had major surgery (<3 weeks prior to first dose).
Have received at least 1 prior systemic therapy in the metastatic or unresectable disease setting; patients who have recurred within six months of adjuvant chemotherapy are not required to have received an additional line of chemotherapy
Patients must have received no previous radiotherapy, surgery, chemotherapy or investigational therapy for the treatment of metastatic disease.
Prior chemotherapy for metastatic CRPC; prior neoadjuvant chemotherapy or chemotherapy for metastatic hormone sensitive prostate cancer are allowed so long as this treatment was completed at least 6 months prior to initiation of sipuleucel-T
Only one line of prior systemic treatment for metastatic urothelial cancer. Participants who received neoadjuvant or adjuvant chemotherapy and showed disease progression (as defined above), within 12 months of the last dose are considered to have received systemic chemotherapy in the metastatic setting Cohort 1: prior chemotherapy and anti-PD(L)1 [in combination or in maintenance setting] (anti-PD(L)1 alone is allowed only for participants with documented cisplatin ineligibility) and Cohort 2: prior chemotherapy (no prior anti-PD(L)1 treatment)
Must have received at least two one prior line of therapy for mCRPC; a taxane chemotherapy administered for metastatic castration sensitive disease will not count, unless patient develops disease progression within 12 months from the last dose chemotherapy
No prior systemic cancer therapy for recurrent or metastatic disease (except if chemotherapy was part of multimodal treatment completed 6 months prior to enrolment).
Prior or concomitant chemotherapy for metastatic or recurrent disease with the following exceptions:\r\n* Prior chemotherapy for local primary disease is permitted\r\n* Bisphosphonates or receptor activator of nuclear factor kappa-? (RANK) ligand inhibitors are allowed at doses and schedule consistent with the treatment or prevention of osteoporosis
Histologically or cytologically confirmed pancreatic adenocarcinoma with metastasis, who had obtained a best response of at least stable disease (SD) or a partial response (PR) for a period of 2 months with no further shrinkage of ? 20% on scan on their first line of chemotherapy for their advanced metastatic disease. Note: Patients that have had prior chemotherapy as adjuvant or neoadjuvant therapy are permitted.
In dose escalation, patients must have had at least one prior line of chemotherapy for advanced disease or progressed within 6 months of adjuvant therapy (prior chemotherapy and/or anti-EGFR therapy is permitted)
Has pathologically confirmed metastatic pancreatic adenocarcinoma that has progressed after, at least, a first line of standard systemic chemotherapy for the metastatic disease, OR participants with pathologically confirmed metastatic adenocarcinoma of the colon or rectum who have progressed to at least 2 lines of standard systemic chemotherapy for the metastatic disease, OR participants with pathologically confirmed locally advanced or metastatic sqEC that has progressed after at least a first line of standard systemic therapy for metastatic disease. First-line participants can be enrolled if a platinum doublet is contraindicated or refused by the participants, OR pathologically confirmed locally advanced or metastatic sqNSCLC that has progressed after at least 2 lines of standard systemic therapy for metastatic disease.
No prior chemotherapy for locally advanced or metastatic urothelial cancer\r\n* Perioperative chemotherapy previously administered in the neoadjuvant and/or adjuvant setting is permitted\r\n* Prior chemotherapy administered in the context of chemoradiation as definitive treatment for bladder preservation is also permitted, provided that disease progression outside the prior radiotherapy field is demonstrated histologically or cytologically
Subjects must have previously untreated metastatic colorectal cancer and have no contraindications to treatment with the standard of care regimen as determined by the investigator; prior adjuvant therapy is acceptable (including immunotherapy), but must have been completed at least 6 months prior to metastatic disease diagnosis
PRE-SCREENING: Unresectable locally advanced or metastatic pancreatic cancer, confirmed by histology, and at least one but not more than two prior chemotherapy regimens with progression (neoadjuvant chemotherapy would not be counted as a line of therapy)
FULL STUDY INCLUSION CRITERIA: Unresectable locally advanced or metastatic pancreatic cancer and at least one but not more than two prior chemotherapy regimens with progression (neoadjuvant chemotherapy would not be counted as a line of therapy)
Previous disease progression on or intolerance to one line of therapy – either platinum-based or immunotherapy (pembrolizumab or nivolumab); prior chemotherapy in the induction, organ preservation, definitive or adjuvant setting permitted if it was for initial treatment of locally advanced or metastatic disease and completed more than 4 months prior to enrollment on the current study; 2-week washout period prior to treatment start will be required
Patient who received any prior systemic hormonal therapy for advanced breast cancer; no more than one prior regimen of chemotherapy for the treatment of metastatic disease is permitted Note:
Prior therapy\r\n* Arm A: Rebastinib plus paclitaxel: up to two prior non-taxane chemotherapy regimens for metastatic or incurable locally advanced disease permitted (no prior paclitaxel or eribulin); patients with estrogen receptor (ER)-positive disease are required to have relapse or progression on at least one line of endocrine therapy\r\n* Arm B: Rebastinib plus eribulin: up to three prior chemotherapy regimens for metastatic or incurable locally advanced disease permitted (no prior eribulin, but prior paclitaxel allowed): patients with ER-positive disease are required to have relapse or progression on at least one line of endocrine therapy
At least 1 prior systemic therapy for metastatic disease; adjuvant chemotherapy or concurrent chemoradiation for early stage disease does not count as prior therapy unless patients progressed within 6 months of completion of chemotherapy
At least one prior regimen for treatment of recurrent or metastatic disease\r\n* Note: Prior regimen for recurrent or metastatic disease is not required if the patient had disease progression or recurrence during or within the first 6 months following completion of adjuvant or neoadjuvant chemotherapy
Prior chemotherapy for advanced or metastatic disease
Must have received at least one but no more than 3 lines of chemotherapy for advanced breast cancer\r\n* Patients who have developed metastatic disease on adjuvant hormone therapy within 24 months of completing adjuvant chemotherapy are considered to have had one line of chemotherapy and are eligible for this trial
Patients who have had chemotherapy or radiotherapy within 3 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 3 weeks earlier\r\n* For Part I, prior adjuvant therapy with gemcitabine or a fluoropyrimidine therapy is permitted if completed > 6 months prior to recurrence; no prior PARP inhibitor therapy is allowed\r\n* For Part II, no prior PARP inhibitor therapy is permitted; up to two prior treatment regimens are permitted as follows: 1 adjuvant and 1 metastatic; 1 locally advanced and 1 metastatic; or 2 metastatic, or a variation thereof
ARM C COHORT 4: Patients must not have received prior systemic chemotherapy for advanced or metastatic disease; prior adjuvant chemotherapy or concurrent chemotherapy and radiation are allowed if they were completed >= 6 months prior to the diagnosis of recurrent disease
Have had prior chemotherapy for metastatic disease in castration-resistant prostate cancer (prior chemotherapy for hormone-sensitive disease, more than six months prior to registration, is acceptable)
Patients with prior oral or intravenous chemotherapy for metastatic disease\r\n* Patients may have had adjuvant or neoadjuvant chemotherapy, if therapy was completed more than 6 months prior to enrollment\r\n* Patients whose comorbidities prevent them from being able to receive the designated chemotherapy regimen\r\n* Patients who are assigned to receive epirubicin must have cardiac ejection fraction (EF) of 45% or greater
More than one prior chemotherapy line for metastatic disease
No prior chemotherapy for metastatic disease
Stage II: subjects must have received no more than 1 prior chemotherapy regimen for metastatic disease; and no more than 2 cycles of their current platinum chemotherapy regimen for metastatic disease; they must have recovered to < grade 1 from all toxicities related to the prior chemotherapy; patients who have received perioperative (i.e. adjuvant or neoadjuvant therapy) > 1 year prior to being treated with chemotherapy for metastatic disease will be eligible provided any chemotherapy-related toxicity has recovered to specified levels
Have had no prior systemic chemotherapy for metastatic disease; at least 6 months since prior adjuvant chemotherapy. Additional Inclusion Criteria for Cohort 2:
Patients who have metastatic or recurrent disease after previous surgery, radiation therapy, and/or chemotherapy are eligible. In Stage 1, no restriction is placed on the number of prior therapies. In Stage 2, patients may have 0 or 1 prior chemotherapy treatments for adjuvant or metastatic disease and no prior endocrine therapies.
Cholangiocarcinoma cohort specific criteria:\r\n* Patients must have histologically or cytologically documented carcinoma primary to the intra- or extra-hepatic biliary system or gall bladder with clinical and/or radiologic evidence of unresectable, locally advanced or metastatic disease; patients with ampullary carcinoma are not eligible\r\n* Patients must have failed at least one (but no more than 2) prior line of systemic therapy in the advanced disease setting\r\n* Patients who received adjuvant chemotherapy and had evidence of disease recurrence within 6 months of completion of the adjuvant treatment are also eligible; in this case, the adjuvant therapy will count as the minimum required one prior line of therapy; if patient received adjuvant treatment and had disease recurrence after 6 months, patients will only be eligible after failing one regimen of systemic chemotherapy used to treat the (unresectable or metastatic) disease recurrence\r\n* If the patient has had decompression of the biliary tree within the last 14 days, stability of the bilirubin level needs to be confirmed with two measurements that are within 5 to 7 days of each other; (the second measurement must be obtained within 7 days prior to registration); both the first and second measurement must be =< 2.5 x IULN; stability is defined as the second measurement being no more than one point higher than the first
No prior cytotoxic chemotherapy for metastatic disease; prior immunotherapy is permitted
For patients with locally advanced disease, no previous radiotherapy, surgery, chemotherapy, or investigational therapy for the treatment of PDAC is permitted; for patients with metastatic disease, prior treatment for non-metastatic disease with 5-fluorouracil (5-FU) or gemcitabine administered as radiation sensitizer, or as a cytotoxic therapy, in the adjuvant setting is allowed, provided at least 6 months have elapsed since completion of the last dose and no >= grade 2 treatment-related toxicities are present
The subject must have progressive disease following at least one prior line of hormonal or chemotherapy for treatment of their metastatic disease
Prior therapy:\r\n* Patients with recurrent, metastatic triple negative breast cancer must have had at least 1 chemotherapy regimen for metastatic breast cancer or have developed metastatic breast cancer within 1 year of completion of adjuvant chemotherapy\r\n* Prior therapy for high grade serous platinum-sensitive ovarian cancer patients must have included 2 prior platinum-based chemotherapy regimens\r\n* Participants must be at least 4 weeks since prior radiation therapy, 3 weeks since prior chemotherapy, and 6 weeks if the last regimen included carmustine (BCNU) or mitomycin C\r\n* No small-molecular kinase inhibitors or any other type of investigational agent within 4 weeks before the first dose of study treatment or 5 half-lives of the compound or active metabolite, whichever is shorter\r\n* For any hormonal therapy, participants must have stopped them at least 1 week prior to initiating therapy\r\n* Amount of prior radiotherapy: participants may not have had > 25% of their bone marrow radiated
Patients who have had prior chemotherapy for metastatic pancreatic cancer (other than FOLFIRINOX); prior radiation is allowed; chemotherapy for non-metastatic disease is allowed
Patients may have received any number of prior systemic treatment regimens for distant metastatic disease or advanced regional disease; the following prior therapy is permitted in either the adjuvant or metastatic disease setting:\r\n* No prior therapy\r\n* Immunotherapy consisting of interferon-alpha, interleukin-2, GM-CSF, ipilimumab, anti-PD1, cancer vaccines, or other experimental agent\r\n* Cytotoxic chemotherapy consisting of dacarbazine, temozolomide, carboplatin, or paclitaxel alone or in combination\r\n* Targeted therapy with temsirolimus, bevacizumab, or sorafenib
Any number of prior systemic therapies for metastatic/recurrent disease are permitted in both the phase I and II portions of the study; patients need not have received a prior cetuximab-based chemotherapy regimen to be eligible for this trial
No prior chemotherapy for the treatment of metastatic disease at study entry. Adjuvant chemotherapy is permitted providing cytotoxic chemotherapy was completed 12 months prior to starting the study and without disease recurrence.
Subject must have received at least 1 prior systemic regimen for advanced or metastatic disease
Have received no more than one prior systemic chemotherapy regimen in the relapsed or metastatic setting. Prior treatment with no more than one prior immune checkpoint inhibitor is permitted and will not be considered as a line of systemic chemotherapy.
Have received more than one prior systemic chemotherapy regimen for metastatic disease.
Participants may have received 0-1 prior chemotherapeutic regimens for metastatic breast cancer and must have been off treatment with chemotherapy for at least 14 days prior to registration; no prior platinum in the metastatic setting is allowed; prior platinum in the neo/adjuvant setting is permissible, if at least 12 months elapsed since the end of adjuvant therapy to the development of metastatic disease; all toxicities related to prior chemotherapy must have resolved to Common Terminology Criteria for Adverse Events (CTCAE) version (v) 4.0 grade 1 or lower; if a patient recurs within 12 months of neoadjuvant or adjuvant chemotherapy, this will be counted as one line of therapy for metastatic disease
Previously received > 1 course of chemotherapy (not including immunotherapies or targeted therapies) for the treatment of metastatic a. Note: Subjects may have received 1 course of chemotherapy prior to surgery for the treatment of locally advanced disease and 1 course of chemotherapy for the treatment of metastatic BC; however, if surgery could not be performed, this will count as the 1 chemotherapy course allowed prior to study
Part A: Subject must have failed at least one prior chemotherapy regimen for metastatic disease and/or is unfit for cisplatin-based chemotherapy.
For Part B - Subjects must not have received any prior systemic treatment for metastatic MCC. Prior chemotherapy treatment in the adjuvant setting (no clinically detectable disease; no metastatic disease) is allowable if the end of treatment occurred at least 6 months prior to study start)
No prior systemic chemotherapy for recurrent or metastatic disease
Patient must have received no prior radiotherapy, surgery, chemotherapy, or investigational therapy for the treatment of metastatic disease.
Progression on at least one prior systemic chemotherapy for advanced, unresectable or metastatic disease; prior adjuvant or neoadjuvant therapy is not included as prior systemic chemotherapy unless treatment occurred within the 6 months prior to study enrollment\r\n* There is no limit to the number of prior lines of treatment a patient has received\r\n* No treatment with biologic therapy, immunotherapy, chemotherapy, investigational agent for malignancy, or radiation =< 28 days before study registration; no treatment with nitrosourea or mitomycin =< 42 days before study registration\r\n* Patients should have resolution of any toxic effects of prior therapy (except alopecia) to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4.0, grade 1 or less
Prior chemoradiotherapy for a pelvic recurrence is permitted. Prior chemotherapy in the adjuvant setting for Stage I, II or III disease is permitted. Note: No prior chemotherapy in the setting of Stage IV disease is permitted unless the patient was without evidence of disease at the completion of chemotherapy and had at least six months of progression-free survival since the completion of chemotherapy. Regardless of circumstances, no more than one prior chemotherapy regimen (including chemo-radiotherapy) is permitted.
Patients must have had one or two prior regimens of systemic chemotherapy for metastatic or locally advanced, unresectable disease; (a maintenance regimen of 5-fluorouracil or capecitabine, with or without bevacizumab, should not be counted as a separate line of treatment); prior treatment with irinotecan is allowed; prior treatment for metastatic disease is not required for patients who experienced disease recurrence during or within 6 months of completion of adjuvant chemotherapy
Prior Therapy:\r\n* No more than two regimens in the metastatic setting as long as patients have adequate performance status; patients with no prior chemotherapy for metastatic disease may be included in the trial if they received anthracyclines and taxanes in the adjuvant or neoadjuvant settings; chemotherapy naïve patients with metastatic disease must have failed anthracyclines and taxanes\r\n* Chemotherapy treatment prior to enrollment must be discontinued for at least 3 weeks prior to study entry\r\n* Patients must have completed radiation therapy at least 21 days prior to beginning protocol treatment
Prior therapy with more than one line of cytotoxic chemotherapy following diagnosis of advanced/metastatic disease, or disease which has progressed despite prior fulvestrant therapy.
Prior treatment with greater than (>) 1 cytotoxic chemotherapy regimen or >2 endocrine therapies for advanced or metastatic disease
Have had no prior systemic therapy for advanced or metastatic disease. Prior adjuvant therapy should have been completed at least 9 months from documentation of metastatic disease. Prior palliative radiotherapy allowed if toxicities resolved to grade 1 or baseline.
Prior therapy with ? 1 systemic chemotherapy regimen for unresectable or metastatic pancreatic cancer or unwilling/unable to receive systemic chemotherapy
Patients must have been treated with at least one prior systemic treatment for incurable advanced or metastatic SCCA of the anal canal; prior treatment for metastatic disease is not required for patients who develop new metastatic lesions during or within 6 months of completion of chemoradiation for limited-stage disease; patients who receive chemotherapy for incurable advanced or metastatic SCCA of the anal canal must wait a minimum >= 28 days (6 weeks for nitrosoureas or mitomycin C) after the date of completion of chemotherapy prior to initiating treatment with nivolumab on this study; patients who undergo radiotherapy to a site of tumor must wait a minimum >= 3 months from the date of completion of radiotherapy prior to initiating treatment with nivolumab on this study
Have received and failed only 1 prior chemotherapy regimen for metastatic pancreatic cancer\r\n* Must have received and failed only 1 prior regimen administered for pancreatic cancer in the metastatic setting; failure includes development of metastases on or within 3 months of adjuvant chemotherapy treatment or development of metastases on or within 3 months of treatment for locally advanced disease or radiographic disease progression on or within 3 months of treatments for metastatic disease; documented intolerance (grade 3 or 4 toxicity or hospitalization leading to discontinuation) of treatment for metastatic disease will also be considered a failure\r\n* Radiosensitizing doses of chemotherapy are not considered systemic chemotherapy
Patients are allowed to have had a maximum of 1 prior chemotherapy regimen for metastatic disease; patients are allowed to have a maximum of two prior regimens if they previously received neoadjuvant/adjuvant chemotherapy or chemoradiotherapy for their initial localized disease
Prior chemotherapy for metastatic disease
No prior chemotherapy for metastatic disease
Prior systemic chemotherapy for metastatic disease
Up to one prior line of chemotherapy for advanced disease is allowed; if received, prior chemotherapy must be discontinued at least 14 days prior to initiation of protocol therapy
Documented, progressive disease/tumor growth, which may include after exposure to a platinating agent (e.g. cisplatin or carboplatin) or another cytotoxic chemotherapy or radiation in a prior line of therapy, or documented intolerance to such an agent; prior line of therapy may include induction chemotherapy or chemoradiotherapy, in addition to treatment for recurrent/metastatic disease; de novo metastatic disease is also allowed as long as progressive disease/evidence of tumor growth is documented
Patients with metastatic or advanced-stage malignant tumor. Patients may have received up to 2 prior lines of chemotherapy for their metastatic disease
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);
Patients must have had one prior systemic chemotherapeutic regimen for management of advanced, metastatic, or recurrent carcinoma of the cervix\r\n* Chemotherapy administered concurrent with primary radiation (e.g.; weekly cisplatin) is not counted as a systemic chemotherapy regimen for management of advanced, metastatic, or recurrent disease; adjuvant chemotherapy given following the completion of radiation therapy (or concurrent chemotherapy and radiation therapy) is not counted as a systemic chemotherapy regimen for management of advanced, metastatic, or recurrent disease (e.g.; paclitaxel and carboplatin for up to 4 cycles)
Subjects must have recurrent, unresectable, or metastatic cervical cancer and have relapsed after a platinum-containing doublet administered for treatment of advanced (recurrent, unresectable, or metastatic) disease. Subjects must have persistent, recurrent, or metastatic squamous cell carcinoma, adenosquamous carcinoma or adenocarcinoma of the cervix, with documented disease progression (disease not amenable to curative therapy). Note: The following cervical tumors are not eligible: minimal deviation/adenoma malignum, gastric type adenocarcinoma, clear cell carcinoma and mesonephric carcinoma. Histologic confirmation of the original primary tumor is required via pathology report. Subjects must have had one prior systemic chemotherapeutic regimen for management of persistent, recurrent, or metastatic carcinoma of the cervix (e.g., paclitaxel/cisplatin, paclitaxel/cisplatin/bevacizumab). Chemotherapy administered concurrently with primary radiation (e.g., weekly cisplatin) is not counted as a systemic chemotherapy regimen. Adjuvant chemotherapy given following completion of radiation therapy (or concurrent chemotherapy and radiation therapy) is not counted as a systemic chemotherapy regimen (e.g., paclitaxel and carboplatin for ?4 cycles). Note: Subjects who have received >1 prior regimen are not eligible.
Patients who have received more than one chemotherapy regimen for metastatic disease
Prior palliative chemotherapy for metastatic or recurrent disease
At least 1 prior antineoplastic chemotherapy treatment regimen for metastatic disease and at least 1 prior treatment with a trastuzumab-containing regimen for at least 6 weeks, for metastatic disease or subject relapsing under adjuvant treatment (part 2 only).
More than 2 prior antineoplastic treatment regimens (excluding hormonotherapy) for metastatic disease. Subjects who relapsed under adjuvant treatment shouldn't have received more than one line of chemotherapy for metastatic disease (part 2 only).
No prior systemic chemotherapy for patients who present with metastatic disease. For patients with recurrent head and neck squamous cell carcinoma, prior chemotherapy is allowed if it was given as part of their definitive therapy. If patients have received prior combined modality therapy, they must be off therapy for at least 6 months.
Patient must have received no previous radiotherapy, surgery, chemotherapy or investigational therapy for the treatment of metastatic disease.
Received more than 1 prior regimen for advanced or metastatic disease.
No prior therapy for metastatic disease except \r\n* For Group A: > 6 months since completion of adjuvant chemotherapy\r\n* For Group B: those patients who enroll just after completing bevacizumab plus either FOLFOX or FOLFIRI
Subjects with histologically confirmed stage IV or recurrent NSCLC (per the 7th International Association for the Study of Lung Cancer classification squamous or nonsquamous histology, with no prior systemic anticancer therapy (including EGFR and ALK inhibitors) given as primary therapy for advanced or metastatic disease\r\n* Prior adjuvant or neoadjuvant chemotherapy is permitted as long as the last administration is at least 2 months prior to enrollment\r\n* Prior definitive chemoradiation for locally advanced disease is also permitted as long as the last administration of chemotherapy or radiotherapy (whichever was given last) occurred at least 2 months prior to enrollment
No prior systemic chemotherapy or WEE1 kinase inhibitor therapy for metastatic or recurrent disease will be allowed; patients are permitted to have received prior systemic chemotherapy as a part of the initial multimodality treatment for locally advanced disease if this treatment was completed more than 6 months prior to enrollment
Received more than 1 prior regimen for advanced or metastatic disease.
Patient treated with more than one prior chemotherapy regimen for recurrent/metastatic disease
For urothelial cancer patients, no prior combination systemic chemotherapy for metastatic disease, except:\r\n* Single-agent radiosensitizing chemotherapy is not considered prior systemic therapy\r\n* Prior neoadjuvant or adjuvant systemic chemotherapy (including cisplatin-based) is allowed provided it was completed >= 6 months prior to the diagnosis of metastatic disease\r\n* Prior intravesical therapy is permitted
For non-urothelial cancer patients, no more than 1 prior line of combination systemic chemotherapy for metastatic disease is allowed
A single regimen of prior chemotherapy for metastatic melanoma is allowed; patients also may have received other immunotherapy or biologic therapy (including kinase inhibitors, antibodies to checkpoints CTLA4, PD1, PDL1, etc.) for metastatic melanoma and there is a limit of three therapy regimens
For participants who present with de novo metastatic disease, no prior systemic chemotherapy is allowed
Received no prior chemotherapy for advanced or metastatic disease (Part 2 and Part 2a)
May have received ?1 prior systemic chemotherapy regimen for metastatic disease.
Patients may not have received more than two prior systemic treatment regimens for distant metastatic disease; the following prior therapy is permitted in either the adjuvant or metastatic disease setting:\r\n* No prior therapy\r\n* Immunotherapy consisting of interferon, interleukin-2, filgrastim (GM-CSF), ipilimumab, anti-programmed death (PD)1 or other experimental agent\r\n* Cytotoxic chemotherapy consisting of dacarbazine, temozolomide, carboplatin +/- paclitaxel
Prior systemic therapy (including chemotherapy, biological or hormonal therapy) will be permitted for palliative treatment of metastatic or unresectable relapsed disease; additionally, previous chemotherapy delivered with curative-intent (i.e., chemoradiotherapy or adjuvant [postoperative] chemotherapy at a time disease was considered potentially curable) will be permitted; prior taxane (including paclitaxel or docetaxel) and/or platinum exposure will be permitted; however, patients must not have experienced disease progression within 3 months of platinum-based therapy; at least 4 weeks must have elapsed since prior chemotherapy or radiation therapy, 6 weeks if the last regimen included carmustine (BCNU) or mitomycin C; toxicities from prior anticancer therapy must have recovered to =< grade 1
Patient may not have previously received chemotherapy for metastatic disease, except adjuvant therapy completed at least 6 months before the first evidence of metastasis
Patients with metastatic disease who are eligible for first line FOLFOX chemotherapy. Adjuvant or neoadjuvant given at least 12 months prior for non-metastatic disease is permitted.
Phase II: Patient who recurs with metastatic disease =< 6 months of completing adjuvant chemotherapy after curative-intent surgical resection is not eligible; patients who recur with metastatic disease > 6 months after completion of adjuvant chemotherapy are eligible
No prior chemotherapy for metastatic disease
Participants are allowed to have received up to 2 prior lines of chemotherapy in the metastatic setting; if a prior chemotherapy was given for less than 1 cycle, it will not be counted as a prior line; the last dose of chemotherapy must be =< 14 days prior to initiation of study therapy; participants should be adequately recovered from acute toxicities of prior treatment; no prior treatment with eribulin mesylate is allowed
Prior treatment with >1 chemotherapy regimen for metastatic disease
Prior chemotherapy for metastatic breast cancer (MBC) (prior adjuvant chemotherapy permitted as long as > 12 months [mo])
Have had prior chemotherapy for metastatic disease in castration-resistant prostate cancer (prior chemotherapy for hormone-sensitive disease, more than twelve months prior to registration, is acceptable)
Patient must NOT have a history of > 1 line of administered chemotherapy for metastatic disease and must be off chemotherapy for a minimum of 2 weeks; prior chemotherapy in the adjuvant setting is allowed
Patients initially diagnosed with locally advanced pancreatic cancer who have undergone chemotherapy then resection and were with no evidence of disease are eligible if metastatic relapse of disease has occurred and if the last dose of chemotherapy was more than 4 months before the data of study entry.
Criteria 3, Participants had disease progression during or after one or more prior standard of care systemic anti-cancer therapy (eg chemotherapy, targeted therapy) for metastatic disease
One, 2, or 3 prior lines of chemotherapy for metastatic disease and with progression of disease on last treatment regimen.
Histologically or cytologically confirmed diagnosis of advanced or recurrent (Stage IIIB not amenable for multimodality treatment) or metastatic (Stage IV) NSCLC that is ALK-positive by an FDA-approved assay performed centrally. Patients must be ALK positive by local test prior to submitting tissue to the central lab. Randomization will occur after ALK positive confirmation is received from the central lab. Patients may have received up to 1 prior chemotherapy regimen for metastatic disease, which may also include maintenance therapy. Note that patients that have received adjuvant or neoadjuvant chemotherapy and developed metastatic disease within 6 months from the end of that therapy would be considered to have received 1 prior regimen for metastatic disease.
Patients may have received up to one prior systemic therapy for advanced or metastatic renal cell carcinoma with the exception of another VEGF inhibitor Food and Drug Administration (FDA)-approved for advanced RCC (i.e., pazopanib, bevacizumab, sorafenib or axitinib); if a patient develops metastatic disease within six months of discontinuation of adjuvant therapy, this will constitute one prior systemic therapy for advanced or metastatic renal cell carcinoma (RCC); if a patient develops metastatic disease and more than six months has elapsed since discontinuation of adjuvant therapy, this will not constitute prior systemic therapy for advanced or metastatic RCC; patients may have also received prior immunotherapy; patients must not have received a MET/hepatocyte growth factor (HGF) inhibitor or sunitinib as prior therapy; at least 14 days must have elapsed since completion of prior systemic therapy; patients must have recovered from all associated toxicities at the time of registration
Documented evidence of advanced RCC
More than 1 prior VEGF-targeted treatment for advanced RCC
During dose escalation only, an additional population with unresectable advanced and/or metastatic 2nd line RCC patients is allowed
Patients must have histologically or cytologically confirmed papillary RCC\r\n* Patients with bilateral multifocal disease can have tumors localized to the kidney or have metastatic disease\r\n* Patients with sporadic papillary RCC (but without multifocal disease) should have advanced disease that is considered unresectable
Diagnosis of advanced RCC associated with HLRCC (cohort 1) or sporadic/non-HLRCC papillary RCC (cohort 2)
Cohort C: advanced or metastatic (stage 4) RCC
Prior systemic treatment of any kind or radiotherapy for RCC
Has at least 1 measurable solid RCC tumor and no RCC tumor that requires immediate surgical intervention. The diagnosis of RCC can be radiologic (histologic diagnosis not required). Patients may have VHL disease-associated tumors in other organ systems
Has received no prior systemic therapy for advanced RCC.
Has received prior radiotherapy for RCC.
Advanced or metastatic RCC
No more than three total prior systemic treatment regimens in the advanced or metastatic RCC setting
Prior systemic therapy for advanced RCC; however, treatment with immunotherapy (i.e., high-dose bolus IL-2, ipilimumab + nivolumab, etc.) is allowed
Metastatic RCC
Prior use of systemic checkpoint inhibitors for the management of metastatic RCC is excluded; prior IFN-alpha or IL-2 is allowed
Radiotherapy for RCC within 14 days of first study treatment with the exception of a single fraction of radiation administered for palliation of symptoms
Patient has received prior treatment for RCC including surgery, radiation, thermoablation or systemic therapy
Prior systemic therapy directed at advanced or metastatic RCC
Must not have had prior systemic therapy for stage IV RCC (except for nivolumab as part of part A of this protocol)
PHASE I: Histologically confirmed advanced RCC of any subtype
PHASE II: Advanced RCC associated with 1) HLRCC or SDH (Cohort 1); OR 2) advanced non HLRCC-related papillary RCC (Cohort 2)
RENAL CELL CARCINOMA (RCC) COHORT INCLUSION CRITERIA: History of histologically-proven locally advanced or metastatic (cT2a-T4NanyMany) chromophobe RCC
(Dose levels 1 and 2) - may have received one or more systemic treatments or regimens for metastatic RCC; (dose level 3) - cannot have received prior systemic treatment for RCC
Metastatic RCC
Recurrent, unresectable, or metastatic RCC or STS (any histologic type) for which pazopanib is an appropriate therapy
Advanced or metastatic RCC
Histologically confirmed, previously untreated (treatment-naive) RCC
No prior systemic therapy for RCC except for one prior adjuvant or neoadjuvant therapy for completely resectable RCC
Phase 2 expansion: RCC
Patient must not have received any prior or concurrent systemic therapy for RCC; adjuvant placebo administration is permitted
For RCC:
Has received no prior systemic therapy for advanced RCC. Prior neoadjuvant/adjuvant therapy for RCC is acceptable if completed >12 months prior to allocation.
Has received no prior systemic therapy for advanced RCC.
Subjects with metastatic RCC who have failed 2 or 3 prior systemic regimens, one of which includes a VEGFR TKI other than sorafenib or tivozanib.
More than 3 prior regimens for metastatic RCC.
RCC subjects must have received ?1 prior line of therapy for metastatic disease (Part 1A)
Prior systemic therapy directed at advanced RCC.
No prior systemic therapy for RCC with the following exception:
Prior treatment with systemic therapy for advanced RCC
For subjects with metastatic RCC who have had no prior systemic treatment for RCC and are considered a poor risk according to Motzer criteria, defined by having >= 3 of the following 5 risk factors for short survival: Karnofsky performance score < 80%, lactate dehydrogenase (LDH) > 1.5 X of ULN, hemoglobin < lower limit of normal (LLN), corrected serum calcium > 10 mg/dL (2.5mM), a time from initial diagnosis of RCC to initiation of systemic therapy of < 1 year
Advanced/metastatic RCC
Subjects enrolled in the I-1, I-3 expansion arms and IN-3 addition arms must not have received any prior systemic therapy for RCC with the following exceptions:
Subjects must have a pathologic diagnosis of advanced renal cell carcinoma (RCC), with histological or cytological confirmation of RCC and must have failed at least 1 prior line of anti-VEGF therapy (including but not limited to sunitinib, and/or sorafenib, and/or bevacizumab and/or pazopanib, and/or axitinib) and must not have received prior therapy with a TORC1 inhibitor (such as temsirolimus or everolimus); or
Subjects must have a pathologic diagnosis of advanced renal cell carcinoma (RCC) and must have progressed on treatment with a TORC1 inhibitor (such as temsirolimus or everolimus).
Have localized non-metastatic renal cell carcinoma (RCC) (< pT2, NO, MO), as per the American Joint Committee on Cancer (AJCC) seventh (7th) edition criteria; patients who have not had a biopsy must have a solid renal mass suggestive of RCC with confirmation of RCC at screening biopsy
Have metastatic RCC with primary tumor in place
1-2 lines of prior therapy for advanced or metastatic RCC including at least one antiangiogenic therapy or nivolumab + ipilimumab
Phase 2: Subjects with advanced or metastatic urothelial carcinoma or RCC.
Patients must not have received systemic therapy for RCC within four weeks prior to registration
Renal Cell Carcinoma (RCC): --Histologic diagnosis of either clear-cell or papillary RCC (metastatic and unresectable, or bilateral, multifocal, unresectable RCC localized to kidneys).
Metastatic or locally advanced unresectable RCC. NOTE: Prior nephrectomy is not mandatory.
Radiotherapy for RCC within 14 days of first study treatment with the exception of a single fraction of radiation administered for palliation of symptoms
LOCALIZED RCC TREATED WITH PARTIAL NEPHRECTOMY:\r\nHave primary or suspected diagnosis of RCC, with presence of cT1-2 renal mass by diagnostic computed tomography (CT) assessment
LOCALIZED RCC TREATED WITH PARTIAL NEPHRECTOMY:\r\nScheduled for partial nephrectomy of renal mass
LOCALIZED RCC TREATED WITH PARTIAL NEPHRECTOMY:\r\nExpected survival of at least 3 months
LOCALIZED RCC TREATED WITH PARTIAL NEPHRECTOMY:\r\nWritten informed consent available
LOCALIZED RCC TREATED WITH PARTIAL NEPHRECTOMY:\r\nEastern Cooperative Oncology Group (ECOG) =< 1
LOCALIZED RCC TREATED WITH PARTIAL NEPHRECTOMY:\r\nNegative serum or urine pregnancy test within 24 hours for females of child bearing age
LOCALIZED RCC TREATED WITH PARTIAL NEPHRECTOMY:\r\nRecovered from toxicity of any prior therapy to >= grade 1
ADVANCED RCC TREATED WITH RADICAL NEPHRECTOMY:\r\nHave pathologic or suspected diagnosis of RCC with presence of cT1-4 renal mass and evidence of nodal or metastatic involvement by diagnostic CT assessment
ADVANCED RCC TREATED WITH RADICAL NEPHRECTOMY:\r\nScheduled for radical nephrectomy and lymph node dissection
ADVANCED RCC TREATED WITH RADICAL NEPHRECTOMY:\r\nExpected survival of at least 3 months
ADVANCED RCC TREATED WITH RADICAL NEPHRECTOMY:\r\nECOG =< 2
ADVANCED RCC TREATED WITH RADICAL NEPHRECTOMY:\r\nNegative serum or urine pregnancy test within 24 hours for females of child bearing age
ADVANCED RCC TREATED WITH RADICAL NEPHRECTOMY:\r\nRecovered from toxicity of any prior therapy to >= grade 1
ADVANCED RCC TREATED WITH RADICAL NEPHRECTOMY:\r\nWritten informed consent available
Previously received cryotherapy of RCC
Advanced or Metastatic renal cell carcinoma (RCC)
Patients must have had =< 1 prior cytotoxic regimen for metastatic disease (unless enrolling in the Progressive Brain Metastases Cohort); note that endocrine and immunotherapies do not count as cytotoxic regimens
For dose-expansion cohort only: no more than two prior systemic chemotherapy-containing regimens in the advanced/metastatic setting (excluding trastuzumab emtansine, which is considered a targeted cytotoxic agent)
Receipt of more than 3 prior regimens of cytotoxic chemotherapy for metastatic disease unless prior approval is granted by the Sponsor.
Part A) Triple-negative disease (ER/PR/HER2-negative) and received at least 2 prior cytotoxic regimens in the incurable, unresectable, LA/MBC setting; or ER-positive and/or PR-positive/HER2-negative disease and received at least 2 prior cytotoxic regimens in the incurable, unresectable, LA/MBC setting and are no longer a candidate for hormonal therapy (not enrolling new patients);
Part B) Combination Arm: HER2-positive disease and received at least 2 prior cytotoxic regimens in the incurable, unresectable, LA/MBC setting (not enrolling new patients);
Up to 3 prior cytotoxic chemotherapeutics regimens or myelosuppressive therapies in the advanced setting.
No more than two prior lines of cytotoxic-containing chemotherapy regimens for advanced disease. There is no limit for prior targeted therapy, hormonal therapy and immunotherapy (such as nivolumab).
More than two prior cytotoxic chemotherapy regimens for the treatment of mCRPC
Patients must have NOT received more than two total prior lines of cytotoxic chemotherapy for management of recurrent or persistent disease, including re-treatment with initial chemotherapy regimens
No more than 3 prior regimens of cytotoxic chemotherapy unless approved by the sponsor (Note: all platinum-containing regimens are not to be counted separately but are considered to be a single regimen for the purposes of this criterion)
Patient must have received =< 3 prior cytotoxic regimens in the metastatic setting
For both the extension and expansion cohorts, patients must have received or refused first line standard systemic therapy for their metastases (if applicable) and patients (pancreatic and esophageal cancers) must have received no more than two prior cytotoxic chemotherapy regimens in the last two years after standard therapy; patients (breast, ovarian and gastrointestinal cancers) must have received no more than three prior cytotoxic chemotherapy regimens in the last two years after standard therapy
Patients who have received more than 2 systemic cytotoxic chemotherapy regimens for metastatic urothelial carcinoma\r\n* Note: prior perioperative chemotherapy is allowed and is not counted as a line of therapy
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.
No more than 5 total previous regimens of systemic therapy, including cytokines and cytotoxic chemotherapy.
More than 3 prior systemic anti-cancer therapies (e.g. cytotoxic agents, biologic agents) regimens for metastatic disease
Patients are allowed to have received up to three prior cytotoxic regimens for treatment of their epithelial ovarian, fallopian tube, or primary peritoneal cancer; they must have had one prior platinum-based chemotherapeutic regimen for management of primary disease, possibly including intra-peritoneal therapy, consolidation, biologic/targeted (non-cytotoxic) agents or extended therapy (maintenance/consolidation) administered after surgical or non-surgical assessment; patients are allowed to have received, but are not required to have received, one to two cytotoxic regimens for management of recurrent or persistent disease; (for the purposes of this study poly adenosine diphosphate [ADP] ribose polymerase [PARP] inhibitors given for recurrent or progressive disease will be considered cytotoxic; PARP inhibitors given as maintenance therapy in continuation with management of primary disease will not be considered as a separate cytotoxic regimen); if two cytotoxic regimens had been received for management of recurrent or persistent disease, one of these regimens would have had to contain either a platinum or a taxane agent
Patients who have received more than 2 prior non-docetaxel containing cytotoxic chemotherapy regimens for Metastatic Castration-Resistant Prostate Cancer (mCRPC).
Up to 2 prior cytotoxic regimens for advanced or metastatic breast cancer patients with no prior cytotoxic regimens for advanced or metastatic disease will only be allowed if they relapsed during or within 12 months of (neo-) adjuvant cytotoxic therapy that included a taxane and/or anthracycline, if not contraindicated.
Participants must have received no more than 3 prior chemotherapy or cytotoxic regimens; there is no limit to the number of prior hormonal therapies
Inclusion Criteria.\n\n          -  Have a diagnosis of Hormone Receptor Positive (HR+), Human Epidermal Growth Factor\n             Receptor 2 Negative (HER2-) breast cancer.\n\n          -  Recurrent, locally advanced, unresectable or metastatic breast cancer with disease\n             progression following anti-estrogen therapy.\n\n          -  Prior treatment with at least 2 chemotherapy regimens:\n\n               -  At least 1 of these regimens must have been administered in the metastatic\n                  setting.\n\n               -  At least 1 of these regimens must have contained a taxane.\n\n               -  No more than 2 prior chemotherapy regimens in the metastatic setting.\n\n          -  Have a performance status (PS) of 0 to 1 on the Eastern Cooperative Oncology Group\n             scale.\n\n          -  Have discontinued all previous therapies for cancer.\n\n          -  Have the presence of measureable disease as defined by Response Evaluation Criteria in\n             Solid Tumors Version 1.1.\n\n        Exclusion Criteria:\n\n          -  Have either a history of central nervous system (CNS) metastasis or evidence of CNS\n             metastasis on the magnetic resonance image of brain obtained at baseline.\n\n          -  Received prior therapy with another cyclin-dependent kinases 4 and 6 (CDK4/6)\n             inhibitor.\n\n          -  Have received treatment with a drug that has not received regulatory approval for any\n             indication within 14 or 21 days of the initial dose of study drug.\n\n          -  Have had major surgery within 14 days of the initial dose of study drug.\n\n          -  Have a history of any other cancer (except non-melanoma skin cancer or carcinoma\n             in-situ of the cervix).
Participants may have had up to two previous cytotoxic therapeutic regimens provided these were discontinued >= 4 weeks before starting the trial
Experienced progression after one or more prior regimens of cytotoxic chemotherapy
Patients who have had 2 or more regimens containing cytotoxic chemotherapy for metastatic melanoma.
Patient must have received =< 3 prior cytotoxic regimens for metastatic breast cancer; this does not include cytotoxic regimens used in the adjuvant setting
More than 4 prior cytotoxic chemotherapy regimens
Patients may not have received more than 2 prior cytotoxic regimens
Patients are allowed to have previously received, but are not required to receive, one or two additional cytotoxic regimens for management of recurrent or metastatic disease according to the following definition: cytotoxic regimens include any agent that targets the genetic and/or mitotic apparatus of dividing cells, resulting in dose-limiting toxicity to the bone marrow and/or gastrointestinal mucosa
More than 2 prior cytotoxic chemotherapy regimens for relapsed or metastatic disease
Received at least two prior systemic cytotoxic chemotherapy regimens for unresectable, locally advanced or metastatic disease.
At least one of the prior systemic cytotoxic chemotherapy regimens for unresectable, locally advanced or metastatic disease must have contained gemcitabine and have met the following criteria:
Subject has received more than 5 prior cytotoxic agent-containing regimens.
May be systemic naïve or received up to two previous systemic treatment regimens for metastatic melanoma.
Prior treatment with more than two regimens of systemic cytotoxic chemotherapy for locally recurrent or metastatic disease
More than two regimens of systemic cytotoxic chemotherapy for recurrent or advanced NSCLC
Receipt of 2 or more prior cytotoxic chemotherapy regimens for advanced, recurrent, or metastatic endometrial cancer.
Patients may have received, but are not required to have received, one or two additional cytotoxic regimens for management of recurrent or persistent disease
More than two regimens of cytotoxic chemotherapy for the treatment of locally advanced or metastatic cancer
Prior treatment with greater than (>) one cytotoxic chemotherapy regimens or experienced recurrent or progressive disease on > two endocrine therapies for MBC
More than 2 prior cytotoxic chemotherapy regimens for recurrent or metastatic disease
Patients may not have received more than 2 prior cytotoxic regimens
There is no limit to the number of prior lines of treatment a patient has received
There is no limit to the number of prior lines of treatment a patient has received
H&N, NETs, biliary tract, CUP: one or two prior chemotherapy-containing lines
Diagnosis of platinum resistant or refractory OVCA having received 2 or fewer prior lines, or recurrent advanced NSCLC having received 3 or fewer prior lines
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;
For Arm B: must have received at least 2 but not more than 4 prior lines of therapy.
Failure or intolerance to at least two prior lines of standard chemotherapies with each containing one or more of the following agents:
CRC - No more than four different prior lines of systemic therapy for advanced disease
Patients must have failed at least 2 lines of stand therapy as outlined for the specific diseases
Cohort 1: Are BRCA negative and have received 3 or more prior lines of therapy.
Cohort 2: Are BRCA negative and have received less than 3 prior lines of therapy.
Has previously received at least 3 lines of myeloma therapy.
Must have had at least two (2) prior lines of systemic therapy for liposarcoma (not to exceed 5 prior lines)
There is no limitation on the number of prior lines of systemic therapy
INCLUSION CRITERIA FOR REGISTRATION (HER2 MUTATION IDENTIFIED BY WASH U GPS LABORATORY): There is no limitation on the number of prior lines of systemic therapy
INCLUSION CRITERIA FOR REGISTRATION (HER2 MUTATION IDENTIFIED AT AN OUTSIDE CLIA CERTIFIED LOCATION): There is no limitation on the number of prior lines of systemic therapy
More than 5 lines of previous cytotoxic therapies. For patients of CTCL who failed romidepsin, more than 4 lines of previous therapies
No more than 3 prior lines of treatment for cGVHD.
The patient has received 1 to 3 prior lines of therapy; by definition, a single line of therapy may consist of 1 or more agents, and may include induction, hematopoietic stem cell transplantation, and maintenance therapy; radiotherapy, bisphosphonate, or a single short course of steroids (i.e., less than or equal to the equivalent of dexamethasone 40 mg/day for 4 days) would not be considered prior lines of therapy
1 to 4 prior lines of therapy
Patients may have received any number of lines of prior systemic therapy for locally advanced/metastatic disease
PHASE IB: =< 2 lines of prior systemic therapy for patients with progressive locally-advanced disease
Patients may have had no more than 3 prior lines of systemic therapy; prior therapy with a MET inhibitor is allowed as long as the patient has not had progressive disease while receiving the agent
Phase II: histologically confirmed colorectal adenocarcinoma post at least two lines of therapy, NSCLC post at least two lines of therapy, or granulosa cell ovarian cancer post at least one line of therapy; patients must have measurable disease
Has received no more than 5 previous lines of chemotherapy and has received at least two lines of chemotherapy in the metastatic setting.
Has received four or more systemic anticancer regimens for mCRPC. Treatment with docetaxel or abiraterone for non-castrate metastatic disease is permissible and does not count towards the lines of therapy for mCRPC. A ‘line’ is a regimen. Combinations of hormones and other types of therapies count as single lines
Have received any number lines of prior systemic therapy (including systemic therapy in the curative intent setting, and including a platinum containing regimen)
One to four prior lines of therapy
Greater than 2 lines of prior systemic therapy for CRPC
ARM I INCLUSION CRITERIA: There are no restrictions on the number of prior lines of treatment for systemic disease
Patients must have had at least 4 prior lines of therapy
Subjects must have received at least one line of systemic therapy in the advanced/metastatic setting. Subjects with diseases without known effective options are also eligible. a) Subjects with relapsed and/or refractory lymphoma must have had at least 2 prior lines of systemic therapy and are not candidates for high dose therapy/autologous stem cell transplant.
Have received no prior lines of systemic therapy and are suitable to receive doxorubicin, ifosfamide and mesna. All previous anticancer treatments must have completed ?3 weeks (21 days) prior to the first dose of study treatment.
More than 2 lines of chemotherapy in the metastatic setting; no limit on endocrine therapy lines; prior exposure to CDK4/6 inhibitor acceptable
More than 5 lines of prior systemic therapy in the preceding three years
Patients must have had at least two, but not more than four prior lines of therapy for their disease, with lines of therapy being separated by the presence of documented disease progression; using this definition, treatment with induction therapy, followed by high dose chemotherapy and autologous stem cell transplantation, and finally by maintenance therapy, would constitute one line, provided that multiple myeloma did not meet criteria for progression at any time during this period
Prior treatment with more than 2 lines of therapy (combination treatments are considered 1 line of therapy)
Patients with R/R PTCL who have received at least one and no more than three previous lines of therapy are eligible to be enrolled in this study
Must be refractory or intolerant to standard lines of therapy
At least one and up to two previous lines of systemic cytotoxic therapy for advanced NSCLC, of which one must have been a platinum-based doublet therapy. Up to four total previous lines of systemic therapy (including immunotherapy and molecularly targeted therapy)
Relapsed disease after at least 2 lines of therapy
Receipt of >/=1 but not more than 3 prior lines of therapy (Cohorts A, B, C, D1, E)
Receipt of >/=4 lines of prior therapy and are refractory to the last line of treatment (Cohort F)
Patients with steroid refractory cGVHD typically have received salvage with multiple lines of therapy; hence in this trial there will be no restriction in terms of prior lines of therapy received; prior ECP exposure is allowed, however prior IL-2 use is excluded
Received less than 4 lines of anti-myeloma therapy
All lines of prior therapy accepted; subjects with prior hepatic or extra-hepatic resections of metastatic disease will be included
In the first 5 patients enrolled in treatment groups on part B of this study (receiving combination ipilimumab and nivolumab), patients may have had 1-0 prior lines of systemic therapy after being diagnosed with metastatic disease; this restriction will be lifted in all subsequent cohorts of patients treated on part B
Patients with solid tumors as described below:\r\n* Inoperable or metastatic (advanced) melanoma:\r\n** Has received, is intolerant, or refused a CTLA-4 inhibitor (ipilimumab) or a PD-1 inhibitor (nivolumab or pembrolizumab) as monotherapy and/or a combination of ipilimumab and nivolumab\r\n** Has received or is intolerant of a BRAF inhibitor or the combination of BRAF and MEK inhibitors for BRAFv600 mutant melanoma and a PD-1 inhibitor as monotherapy or in combination\r\n* Inoperable or metastatic (advanced) ovarian, primary peritoneal or fallopian tube carcinoma:\r\n** Has received platinum containing chemotherapy and has platinum refractory or resistant disease that has progressed on second line therapy\r\n** If platinum sensitive disease, should have received >= 2 lines of chemotherapy\r\n** May have received PARP inhibitors, bevacizumab or other targeted VEGF inhibitor therapy\r\n* Inoperable or metastatic (advanced) synovial sarcoma:\r\n** Should have received and progressed on >= two lines of systemic therapy\r\n* Subjects with other histologies:\r\n** Must have previously received two lines of systemic standard care (or effective salvage chemotherapy regimens) for metastatic disease, if known to be effective for that disease, and have been deemed either non-responders (progressive disease) or have recurred
Patients can have received up to 4 lines of systemic treatment; psoralen plus ultraviolet light therapy (PUVA) is not considered to be a systemic therapy
Patients can have any lines (including zero) of prior therapy to sign consent prior to tissue harvest; vaccination will not take place until at least one line of standard chemotherapy is given
Patients who have received up to two previous lines of systemic chemotherapy are eligible for this trial
Subjects must have had at least three lines of therapy for their disease, including a proteasome inhibitor and immunomodulatory drug (e.g., lenalidomide), with lines of therapy being separated by the presence of documented disease progression; using this definition, treatment with induction therapy, followed by high dose chemotherapy and autologous stem cell transplantation, and finally by maintenance therapy, would constitute one line, provided that multiple myeloma did not meet criteria for progression at any time during this period
To be eligible for Cohorts 1-4, patients must have failed one or two prior lines of systemic therapy for advanced/metastatic disease
Must have undergone prior treatment with ?2 treatment lines of anti-myeloma therapy and failed last line of treatment (disease progression ?60 days of completion of last therapy)
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.
More than three lines of prior therapy.
More than 2 lines of therapy beyond corticosteroids with or without calcineurin inhibitors or sirolimus
Arms 2, 2E, 3, 3E: patients who previously received > 2 lines of systemic chemotherapy for advanced or metastatic disease
There will be no limits to prior lines of treatment
Prior systemic therapy: (a) Phase 1b: Any number of lines of prior therapy; (b) Phase 2: Progressed after 1 or 2 lines of prior chemotherapy
Received no more than 3 prior lines of systemic therapy for metastatic disease.
Patients must have received at least 3 prior lines of therapy (Note: Induction therapy and stem cell transplant ± maintenance will be considered as one line).
Criteria 4 Received at least 1 but not more than 3 prior lines of therapy for multiple myeloma (induction therapy followed by stem cell transplant and consolidation/maintenance therapy will be considered as 1 line of therapy, see Appendix E for guidance)
Refractory to and disease progression within 6 months from the last dose of at least 2 lines of prior therapy
Subjects who have received up to 3 lines of therapy for advanced disease, without prior exposure to taxane in the advanced stage setting
Has received at least 2 prior lines of therapy as described in the protocol.
For Part 1, prior treatment with less than 4 prior lines of chemotherapy
No limits to the prior lines of treatment
Progression on at least two prior lines of therapy for unresectable metastatic colorectal adenocarcinoma\r\n* Administration of bevacizumab previously does not impact study inclusion
RENAL COHORT: Any number of prior treatment lines is allowed on study
Patients can have any lines (including zero) of prior therapy to sign consent prior to tissue harvest
Any number of prior lines of therapy
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
Subjects with one to three lines of therapy for their disease with lines of therapy being separated by the presence of documented disease progression; using this definition, treatment with induction therapy, followed by high dose chemotherapy and autologous stem cell transplantation, and finally by maintenance therapy, would constitute one line, provided that multiple myeloma did not meet criteria for progression at any time during this period
Patient must have received 2 or more prior lines of systemic therapy for myeloma; patients must be off last treatment for at least 2 weeks (wks) by the beginning of treatment on this protocol
Subjects may have received no more than 2 lines of prior therapy for advanced disease.
Subjects may have received no more than 2 lines of prior therapy for advanced disease.
Subjects may have received no more than 2 lines of prior therapy for the advanced disease
previously received at least 1 but no more than 4 lines of therapy, one therapy must have included a VEGF TKI
previously received at least 1 but no more than 3 lines of therapy, one therapy must have included a fluoropyrimidine based regimen
Must have received at least two prior lines of systemic therapy, including at least one VEGFR-targeting TKI (e.g., sunitinib, sorafenib, pazopanib, cabozantinib)
Histologically confirmed metastatic soft tissue sarcoma (i.e., non-GIST, non-adipocytic) that has progressed by RECIST following treatment with anthracycline chemotherapy. Patients may have received up to four lines of systemic therapy for metastatic disease and no more than two lines of combination treatment ( Phase 2 only)
Received prior treatment with at least 1, but no more than 3, prior lines of therapy for MM.
Three or more prior lines of systemic therapy for GBM.
There is no limitation in the number of prior lines of therapy
Had more than 2 prior lines of systemic therapy. Maintenance therapies and hormonal therapies are not considered additional lines of therapy
Must have undergone prior treatment with ?2 treatment lines of anti-myeloma therapy
Has histopathologically confirmed gastric or GEJ adenocarcinoma with documented disease progression after 0-2 prior lines of systemic therapy
Has histopathologically confirmed nonsquamous or squamous NSCLC with documented disease progression after 0-3 prior lines of systemic therapy
Has histologically confirmed biliary tract adenocarcinoma with documented progression after 1-2 prior lines of systemic therapy
Has received ?3 lines of prior systemic therapy for gastric or GEJ adenocarcinoma and BTC or ?4 lines for NSCLC or urothelial cancer.
Patient has had at least 2 or more prior lines of therapy including lenalidomide and bortezomib and has demonstrated disease progression on or within 60 days of completion of the last therapy
No more than 2 prior lines of anti-cancer therapy, one of which must have included pemetrexed and a platinum.
Have received any number lines of prior systemic therapy (including systemic therapy in the curative intent setting)
More than two previous treatment lines of systemic antineoplastic therapies in the advanced setting
More than 2 prior lines of systemic antineoplastic therapies in the advanced setting
MEL subjects may be treatment naïve or may have received prior lines of therapy for metastatic disease (Parts 1A and 1B)
The patient must have received no more than 3 prior lines of therapy for metastatic disease.
The patient must have received no more than 2 prior lines of therapy for metastatic disease.
At least three prior lines of therapy for advanced ovarian cancer as defined in the protocol
Treatment naive patients in first-line or pre-treated patients with no more than 2 lines of prior therapy
Patients in Phase 2 expansion cohort B will have experienced disease progression with 1 or 2 prior lines of therapy, including up to 1 prior line of liver-directed therapy
Received 1 or 2 prior lines of therapy.
More than three prior lines of cytotoxic therapy.
Has histopathologically confirmed gastric or GEJ adenocarcinoma with documented disease progression after 1-2 prior lines of systemic therapy
Has histopathologically confirmed nonsquamous or squamous NSCLC with documented disease progression after 1-3 prior lines of systemic therapy
No more than two prior lines of chemotherapy for metastatic sarcoma are allowed; neoadjuvant/adjuvant chemotherapy with definitive therapy (radiation, surgery or radiation and surgery) will not be counted as one of these prior lines of therapy; non-cytotoxic therapies will not be counted as one of these prior lines of therapy
Pancreatic neuroendocrine patients must have had progression after prior therapy; patients with other foregut neuroendocrine tumors must have had progressive disease over the last 12 months, irrespective of prior therapy; patients with both functional (who may continue somatostatin analogues as required for control of related symptoms) and non-functional tumors are eligible; in patients who have previously received therapy, the number of prior lines of therapy should not be more than 2 lines of systemic therapy not including somatostatin analogues
No more than 2 prior lines of cytotoxic therapy, which should have included pemetrexed and a platinum
Subject that have received more than 2 prior lines of chemotherapy must not have liver metastases
Patients must have received two or more prior lines of treatment. A previous regimen is defined as one of the following: at least two months of single-agent therapy, at least two consecutive cycles of polychemotherapy, autologous transplant, radioimmunotherapy.
Patients must have previously treated relapsed and/or refractory MCL with at least 2 prior lines of therapy (prior carfilzomib, ibrutinib, bortezomib, anthracycline, rituximab or stem cell transplant are acceptable); there is no upper limit for prior lines of therapy
No more than 2 prior lines of systemic chemotherapy for metastatic urothelial cancer
Patients may have received unlimited lines of prior therapy
At least 2 and no more than 3 prior lines of therapy for incurable or metastatic NSCLC
Received more than 3 lines of prior conventional therapy for advanced disease
Unlimited number of lines of endocrine therapy and up to two lines of cytotoxic chemotherapy in the metastatic setting (Phase Ib)
No more than 4 prior lines of systemic anti-cancer therapy.
Male and female, ages 18 and above, with relapsed or refractory FL lymphoma after > or =2 prior treatment lines; each of the 2 prior treatment lines must include at least CD20 antibody and/or an alkylating agent
Symptomatic myeloma that has progressed/relapsed after 1 to 3 prior lines of therapy
One or more prior lines of cytotoxic treatment for advanced disease (prior hormonal therapy is not considered to count as prior lines of therapy)
The patient has received =< 5 lines of prior therapy
PART B: Patients must have received prior platinum-based chemotherapy but may have received any number of other lines of prior therapy
More than 3 prior lines of chemotherapy for recurrent cancer.
Secretory MM for which the patient previously received 1-3 prior lines of therapy (Phase 2).
1-3 prior lines of therapy
May have received up to two prior lines of chemotherapy for advanced disease
Progression on or following, or intolerant of, at least two prior lines of standard systemic therapy for advanced or metastatic colorectal cancers.
More than 2 prior lines of CLL therapy.
All patients may have received up to two prior lines of chemotherapy for recurrent/advanced disease
Patients must have received at least one but no more than 4 prior lines of systemic therapy
For participation in the Phase I portion, patients must have completed either one or two lines of prior therapy
No more than 4 prior lines of systemic anti-cancer therapy.
Subjects who progressed after receiving at least 2, but no more than 3, prior SoC treatment lines
For Phase 1b of the study: Participants who have experienced failure of multiple lines of prior chemotherapy are eligible.
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.
Previously received at least 3, but no more than 6, lines of therapy including at least 1 course of platinum-based therapy
More than three prior lines of chemotherapy
Must have received 2 or 3 prior lines of conventional molecularly targeted therapy
Received at least 2 prior lines of therapy (induction therapy and stem cell transplant ± maintenance are to be considered a single line of therapy).
No more than 3 prior lines of therapy
Patients must have received >= 2 previous lines of therapy that must have included bortezomib and Revlimid; patients must have received 1, but no more than 4 prior treatment regimens or lines of therapy for multiple myeloma; (induction therapy followed by stem cell transplant and consolidation/maintenance therapy will be considered as one line of therapy)
For Part 3, subject has received 4 or more prior lines of cytotoxic chemotherapy for systemic disease.
Received 1, but no more than 3 prior treatment regimens or lines of therapy for multiple myeloma. (Induction therapy followed by stem cell transplant and consolidation/maintenance therapy will be considered as one line of therapy).
Subjects must have undergone prior treatment with ? 2 treatment lines of anti-myeloma therapy