Part A and A2: Participants with one histologically or cytologically confirmed malignant advanced solid tumor, for which no standard therapy is available which may convey clinical benefit
Part B: Participants with one histologically or cytologically confirmed malignant advanced solid tumor, for which no standard therapy is available which may convey clinical benefit and/or participants must have progressed after at least 1 prior chemotherapy regimen in the metastatic setting, and for which carboplatin (for Part B1), gemcitabine (for Part B2), or cisplatin (for Part B3) would be considered standard of care.
Histologically proven, locally advanced unresectable or metastatic solid tumors or hematologic malignancies for whom no approved therapy with demonstrated clinical benefit is available or standard treatment was declined.
Subject must have locally advanced or metastatic solid tumor with no additional therapy options available that are known to provide clinical benefit per institutional standards;
For Part A exclusively (RO6874281 monotherapy), confirmed advanced and/or metastatic solid tumor, with at least one tumor lesion of location accessible to biopsy per clinical judgment of the treating physician, and confirmed progression at baseline; for whom no standard therapy that would confer clinical benefit to the participant exists
Patients who have received standard first-line therapy for metastatic cancer (except for the tumors for which no first-line therapy exists) and in whom a trial of targeted therapy is considered the best available treatment option; eligible patients should not have available therapies that will convey clinical benefit
Pathologically confirmed advanced solid tumor for which standard therapy proven to provide clinical benefit does not exist or is no longer effective.
Patients must have histologically confirmed solid tumor that is metastatic or unresectable, and there is no available therapy likely to convey clinical benefit.
Histologically confirmed diagnosis of advanced or metastatic solid tumors, disease should have progressed following at least one line of therapy and no other standard therapy with proven clinical benefit is available
At least one line of prior combination and no other standard therapy with proven clinical benefit is available.
Must have received at least one prior line chemotherapy regimen and no other standard therapy with proven clinical benefit is available.
Participants must have a histologically or cytologically confirmed advanced solid tumor of a non-breast origin, for which standard therapy proven to provide clinical benefit does not exist or is no longer effective
Histologically proven, locally advanced unresectable or metastatic solid tumors for whom no approved therapy with demonstrated clinical benefit is available or standard treatment was declined.
Patients must have histologically confirmed solid tumor that is metastatic or unresectable, and there is no available therapy likely to convey clinical benefit
Participants who have received standard first-line therapy for metastatic cancer (except for the tumors for which no first-line therapy exists) and in whom a trial of targeted therapy is considered the best available treatment option. Eligible participants should not have available therapies that will convey clinical benefit and/or are not suitable options per the treating physician's judgment
Participants must have a pathologically confirmed advanced solid tumor for which standard therapy proven to provide clinical benefit does not exist or is no longer effective.
The patient must have histologic or cytologic evidence of a malignant solid tumor and must have disease that is resistant to or relapsed following available standard systemic therapy, or for which there is no standard systemic therapy or reasonable therapy likely to result in clinical benefit.
Inclusion Criteria:\n\n          -  Histologically confirmed solid malignancy that is metastatic or unresectable for which\n             standard curative or palliative measures do not exist or are no longer effective (Dose\n             Escalation phase only)\n\n          -  Measurable disease according to RECIST v 1.1\n\n          -  Eastern Cooperative Oncology Group (ECOG) score of 0 or 1\n\n          -  Normal organ and marrow function\n\n        Dose Expansion phase specific additional inclusion criteria:\n\n          -  Patients with metastatic colorectal cancer with no available therapy options that are\n             known to provide clinical benefit per institutional standard of care. (colorectal\n             cancer cohort only)\n\n          -  Patients must have a histologically confirmed epithelial ovarian cancer, primary\n             peritoneal cancer or fallopian tube solid tumor cancer that is locally advanced or\n             metastatic with no available therapy options that are known to provide clinical\n             benefit per institutional standard of care. (ovarian cancer cohort only)\n\n          -  Patients must have histologically or cytologically confirmed cervical squamous cell\n             carcinoma that is locally advanced or metastatic with no available therapy options\n             that are known to provide clinical benefit per institutional standard of care.\n             (cervical cancer cohort only)\n\n          -  Patients must have histologically or cytologically confirmed head and neck squamous\n             cell carcinoma that is locally advanced or metastatic with no available therapy\n             options that are known to provide clinical benefit per institutional standard of care.\n             (various solid tumors cohort: head and neck squamous cell carcinoma groups only).\n\n          -  Patients must have received prior therapy with an anti-PD-1 or anti-PD-L1 antibody, or\n             previously participated in Merck MK 3475 clinical trials. Patients must have\n             experienced documented, confirmed radiographic progression of disease by iRECIST, or\n             by RECIST v1.1 (various solid tumors cohort head and neck squamous cell carcinoma,\n             Check point inhibitor experienced group only).\n\n          -  Patients must have histologically or cytologically confirmed small cell lung carcinoma\n             that is locally advanced or metastatic with no available therapy options that are\n             known to provide clinical benefit per institutional standard of care. (various solid\n             tumors cohort, SCLC group only)\n\n          -  Patients must have histologically or cytologically confirmed cholangiocarcinoma that\n             is locally advanced or metastatic with no available therapy options that are known to\n             provide clinical benefit per institutional standard of care. (various solid tumors\n             cohort, cholangiocarcinoma group only)\n\n          -  Patients must have histologically or cytologically confirmed mesothelioma that is\n             locally advanced or metastatic with no available therapy options that are known to\n             provide clinical benefit per institutional standard of care. (various solid tumors\n             cohort, mesothelioma group only)\n\n          -  Patients must have histologically or cytologically confirmed carcinoma of the\n             esophagus including the gastroesophageal junction that is locally advanced or\n             metastatic with no available therapy options that are known to provide clinical\n             benefit per institutional standard of care. (various solid tumors cohort,\n             gastroesophageal carcinoma group only)\n\n        Exclusion Criteria:\n\n        Exclusion criteria apply to all phases and cohorts in the study unless otherwise stated\n\n          -  Prior monoclonal antibody, within 4 weeks prior to first dose of study drug.\n\n          -  Prior chemotherapy, targeted small molecule therapy or radiotherapy within 2 weeks\n             prior to first dose of study drug.\n\n          -  Patients who have received any other investigational agents within 4 weeks of first\n             dose of study drug.\n\n          -  Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic\n             T-lymphocyte-associated antigen-4 (CTLA-4) antibody. (Not applicable for various solid\n             tumors cohort, head and neck squamous cell carcinoma check-point inhibitor experienced\n             group)\n\n          -  History of allergic reactions attributed to compounds of similar chemical or biologic\n             composition to birinapant or pembrolizumab or their constituents.\n\n          -  Uncontrolled intercurrent illness including, but not limited to, symptomatic\n             congestive heart failure, hypertension, unstable angina pectoris, cardiac arrhythmia,\n             autoimmune disease or inflammatory diseases, or psychiatric illness/social situations\n             that would limit compliance with study requirements.\n\n          -  Evidence of active, non-infectious pneumonitis or a history of interstitial lung\n             disease.\n\n          -  Known history of Human Immunodeficiency Virus (HIV (HIV1/2 antibodies), or Active\n             Hepatitis B (HBsAg reactive. Active Hepatitis C (HCV-RNA qualitative).\n\n          -  Currently breast feeding, pregnant or planning to conceive or father Children from\n             screening through 120 Days after last dose of study drug.\n\n          -  Patients who have received anti-PD-L2, anti-CD137, or anti-Cytotoxic\n             T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other\n             antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways)\n             (Various solid tumor cohort, head and neck squamous cell carcinoma check point\n             inhibitor experienced group only)
Histologically or cytologically confirmed advanced/metastatic solid tumor and refractory to or intolerant of existing therapy(ies) known to provide clinical benefit for the condition of the participant
Histologically-proven, unresectable locally advanced or metastatic solid tumors of any histology that test positive for B7-H3 expression on tumor cells or vasculature for whom no approved therapy with demonstrated clinical benefit is available. For all tumor types, the requirement for previous systemic therapy may be waived if a patient was intolerant of or refused standard first-line therapy
Subjects with histologically or cytologically proven advanced or metastatic solid malignancies for whom no effective standard therapy exists or has failed or subjects who are intolerant to established therapy known to provide clinical benefit for their condition (dose escalation cohorts; Part I).
Subjects must have histologically confirmed malignancy that is metastatic or unresectable and for which there is no available therapy likely to convey clinical benefit.
For the Western safety cohort only: participants with locally advanced or metastatic solid tumor for whom no standard treatment with an established survival benefit is available or if the participant refuses other standard therapy.
Dose escalation cohorts: Patients with histologically or cytologically confirmed diagnosis of malignancy (including lymphoma) with demonstrated progression of a tumor for whom there is no available therapy likely to convey clinical benefit AND who have not been previously treated with a PD-1/PD-L1 inhibitor. These patients do not require measurable disease
Has a histologically- or cytologically-confirmed metastatic solid tumor for which there is no available therapy which may convey clinical benefit. Part E: Has advanced malignant melanoma.
Patients must have metastatic disease that is either refractory to standard therapy or for which no effective standard therapy that confers clinical benefit is available
Have a histologically confirmed diagnosis of an advanced and/or metastatic solid tumor that is relapsed and/or refractory to standard therapy, as defined as progression on at least one prior line of therapy in the relapsed/metastatic setting and no existing options are felt to provide clinical benefit.
Has histologically or cytologically confirmed advanced, unresectable metastatic solid tumor(s) for which the patients have no available therapy likely to provide clinical benefit, or for which paclitaxel is considered a standard of care.
Solid tumor malignancy for which no standard of care therapy is available which has a proven overall survival benefit
Advanced metastatic or unresectable malignancy that is refractory to standard therapy and/or existing therapies are not likely to achieve clinical benefit, and/or the patient declines to receive standard treatment such as chemotherapy.
Subjects must have a histologically confirmed malignancy that is metastatic or unresectable for which there is no remaining standard curative therapy and no therapy with a demonstrated survival benefit or they must be ineligible to receive such therapy and/or have declined all such therapy. In addition, subjects must have a tumor that is at least 1 cm in a single dimension and is radiographically apparent on CT or MRI.
Has histologically or cytologically confirmed advanced, measurable or non-measurable metastatic solid tumors for which the patients have no available therapy to convey clinical benefit Expansion Phase only: The target population should include at least
Histological or cytological confirmation of advanced unresectable solid tumors, including those subjects who have progressed on standard anticancer therapy and for whom no further therapy that confers clinical benefit is available.
Patients enrolled in the dose escalation stages must have disease that is resistant to or relapsed following available standard systemic therapy, or for which there is no standard systemic therapy or reasonable therapy in the physician's judgment likely to result in clinical benefit or if such therapy has been refused by the patient. Documentation of the reason must be provided for patients who have not received a standard therapy likely to result in clinical benefit.
Advanced solid tumor for which, in the opinion of the Investigator, no other standard or investigational therapy offers greater benefit.
Has a histologically- or cytologically-confirmed advanced malignancy that has progressed after standard-of-care therapy/treatments and there is no available therapy likely to convey clinical benefit
Subjects must have no alternate therapy of proven benefit or have refused standard therapy.
Subject must have advanced and/or metastatic, histologically or cytologically documented cancer or lymphomas, for whom there is no available standard therapy shown to provide clinical benefit.
Patients with locally advanced or metastatic HPV associate malignancy (cervical, vaginal, vulvar, penile, anal, or oropharyngeal carcinoma), either refractory to standard therapy or for which no effective standard therapy that confers clinical benefit is available
Patients must have histologically documented solid tumors or histologically confirmed diagnosis of lymphoma or multiple myeloma requiring therapy and meet one of the following criteria:\r\n* Patients must have progressed following at least one line of standard systemic therapy and there must not be other approval/standard therapy available that has been shown to prolong overall survival (i.e. in a randomized trial against another standard treatment or by comparison to historical controls); patients who cannot receive other standard therapy that has been shown to prolong overall survival due to medical issues will be eligible, if other eligibility criteria are met; if the patient is currently receiving therapy, the clinician must have assessed that the current therapy is no longer benefitting the patient prior to enrolling on MATCH, regardless of whether it is considered standard OR\r\n* Patients for whose disease no standard treatment exists that has been shown to prolong overall survival\r\n* NOTE: No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer; in situ cervical cancer; adequately treated stage I or II cancer from which the patient is currently in complete remission; any other cancer from which the patient has been disease-free for 5 years
Patients must have progressed following at least one line of standard systemic therapy and there must not be other approved/standard therapy available that has been shown to prolong overall survival (i.e. in a randomized trial against another standard treatment or by comparison to historical controls); patients who cannot receive other standard therapy that has been shown to prolonged survival due to medical issues will be eligible, if other eligibility criteria are met; OR \r\n* Patients for whose disease no standard treatment exists that has been shown to prolong overall survival
Patient must meet at least one of the following criteria: a. Progressed or recurrent despite standard therapy, b. No standard therapy exists for this malignancy, c. Patient is intolerant of standard therapy, d. Patient is not a candidate for standard therapy, e. For AML and MDS patients: patient is not a candidate for allogeneic hematopoietic stem cell transplantation, f, For sarcoma patients: f-1. Patient has disease that is metastatic or unresectable, f-2. Patient with metastatic disease has had at least one prior line of therapy for metastatic disease, f-3. No curative multimodality options exist
Phase I part: Patients with advanced/metastatic solid tumors, with measurable or non-measurable disease as determined by RECIST version 1.1 (refer to Appendix 1), who have progressed despite standard therapy or are intolerant of standard therapy, or for whom no standard therapy exists.
2. Part A, must have a histologically or cytologically documented, incurable, or metastatic solid tumor that has progressed on, or been intolerant to, all standard systemic therapy options for the tumor type in the metastatic setting, or must have a tumor type for which no such standard systemic option exists;
Subjects with histological- or cytological-confirmed, advanced cancer, who have progressed on (or not been able to tolerate) standard therapy or for whom no standard anticancer therapy exists
Participants must have received, and then progressed, relapsed, or been intolerant to, at least 1 standard treatment regimen in the advanced or metastatic setting according to solid tumor histologies
Participants must have received and then progressed or been intolerant to at least 1 standard treatment regimen in the advanced or metastatic setting if such a therapy exists
Must have progressed following standard therapy, or for whom, in the opinion of the Investigator, no effective standard therapy exists, is tolerated or is appropriate.
Patients with advanced/metastatic cancer, with measurable disease as determined by RECIST version 1.1, who have progressed despite standard therapy or are intolerant to standard therapy, and for whom no effective therapy is available. Patients must fit into one of the following groups:
Disease that has progressed on standard therapy or for whom there is no other therapy option available
Patients without a curative therapy or whose tumor does not have standard chemotherapy
Patients with advanced melanoma, endometrial carcinoma, pancreatic or TNBC, with measurable or non-measurable disease who have progressed despite standard therapy or are intolerant of standard therapy, or for whom no standard therapy exists.
Dose escalation phase only: Subject not responding to standard therapy or for whom no standard treatment exists
Dose expansion phase: Subject not responding to standard therapy or for whom no standard treatment exists with:
Histopathologically confirmed diagnosis of an advanced solid tumor such as breast cancer or midline carcinoma with NUT rearrangement, that has progressed despite standard therapy, or for which no standard therapy exists. For enrollment in the expansion cohorts, histopathological confirmation of triple-negative breast cancer or high-grade serous ovarian cancer is required.
have metastatic or unresectable advanced solid tumors that have recurred or progressed following standard therapy or
Participants must have received, and then progressed, relapsed, or been intolerant to, at least 1 standard treatment regimen in the advanced or metastatic setting according to solid tumor histologies
Participants must have received, and then progressed, relapsed, or been intolerant to, all standard treatment regimens with proven survival benefit in the advanced or metastatic setting according to tumor type, if such a therapy exists
Patients must have histologically confirmed metastatic or unresectable malignancy that is refractory to standard therapy or for which no standard therapy exists and where irinotecan is deemed a reasonable treatment option
Dose expansion groups of FAZ053 single agent and FAZ053 in combination with PDR001: Patients with advanced/metastatic solid tumors with at least one measurable lesion as determined by RECIST version 1.1 who may or may not have received prior treatment with an immune checkpoint inhibitor (for FAZ053 single agent no treatment with an anti-PD-L1 inhibitor is permitted), who have progressed despite standard therapy, or for whom no standard therapy is available and fit into one of the following groups:
Must have progressed following standard therapy, or for whom, in the opinion of the Investigator, no effective standard therapy exists, is tolerated or appropriate.
All patients participating in this clinical trial must have progressed following standard therapy, or for whom, in the opinion of the Investigator, no effective standard therapy exists, is tolerated or appropriate.
Patients must have histologically documented solid tumors whose disease has progressed on standard therapy or for which there is no available standard therapy
Phase I: histologically confirmed solid tumors that have progressed on standard therapy known to prolong survival or for which no standard treatment options exist
Diagnosed with a locally advanced or metastatic malignancy that has progressed despite standard therapy, or for which no effective standard therapy exists
Patient must have an advanced (metastatic or recurrent) pathologically proven solid tumor which has not responded to standard therapy or which has progressed following standard therapy for advanced disease and/or for which no standard therapy is known to be effective; patients in expansion cohort A must have accessible tumor for biopsy
Relapsed following or progressed through standard therapy
Have a disease for which no standard effective therapy exists (i.e., a therapy that demonstrates a significant increase in survival)
Patients for whom no standard curative therapy exists
Part A of the study will include patients that have histological confirmation of a solid malignancy (other than HCC) that is refractory to standard therapy or for which no standard of care regimen currently exists.
Subjects must have received prior standard therapy appropriate for their tumor type and stage of disease, or in the opinion of the Investigator, would be unlikely to tolerate or derive clinical benefit from appropriate standard of care therapy.
Subject has received at least one prior standard therapy (or generally accepted upfront therapy if no standard exists) and have no known curative therapy.
Participants must have received, and then progressed or been intolerant to, at least 1 standard treatment regimen
Diagnosis of O-AML that is refractory to or intolerant to standard therapy and is no longer likely to respond to such therapy (at least one line of therapy); or Diagnosis of MDS/CMML that is refractory to or intolerant to standard therapy and is no longer likely to respond to such therapy (at least one line of therapy)
During dose escalation, subjects with advanced solid tumors that have progressed following at least one standard regimen
All patients participating in this clinical trial must have progressed following standard therapy or, in the opinion of the Investigator, no effective standard therapy exists, is tolerated, appropriate or is considered equivalent to study treatment.
If an approved first-line standard therapy for the patient’s tumor is available, subjects must have failed, be intolerant to, be ineligible for, or have refused that treatment; enrollment of patients for whom no standard therapy exists or who decline standard therapy should be discussed with the principal investigator prior to enrollment; patients must have progressive disease on study entry
All patients must have received prior first line standard therapy or declined standard therapy
Patients for whom no standard curable therapy exists
Diagnosis of one of the following: 1. Part 1: Histologically- or cytological-confirmed diagnosis of non-resectable or metastatic solid malignancy. At the time of enrollment, subjects either: have progressed on prior therapy (radiographic documentation of progression is adequate for study participation) AND have no standard-of-care therapy that would be expected to achieve a durable clinical response, OR refuse standard therapy, OR are not candidates for standard therapy, OR have a disease for which no generally-accepted standard-of-care exists. 2. Part 2: Histologically- or cytologically-confirmed diagnosis of metastatic or non-resectable triple-negative breast cancer (TNBC) (estrogen receptor [ER]-/ progesterone receptor [PR]-/Human Epidermal Growth Factor Receptor 2 [Her2]-, as defined by local laboratory standards); metastatic or non-resectable transitional cell carcinoma of the bladder, ureter, or renal pelvis; recurrent GBM; or non-Hodgkin's lymphoma. At the time of enrollment, subjects either: have progressed on prior therapy (radiographic documentation of progression is adequate for study participation) AND have no standard-of-care therapy that would be expected achieve a durable clinical response, OR refuse standard therapy, OR are not candidates for standard therapy.
Patients must have a histologically-confirmed metastatic or locally advanced solid tumor that has failed to respond to standard therapy, progressed despite standard therapy, or for which standard therapy does not exist
Patient has an advanced malignancy that has progressed or recurred following standard therapy for advanced disease, and for which no curative therapies are available.
Histologically or cytologically documented, locally advanced or metastatic solid malignancy that has progressed on available standard systemic therapy, and for whom no effective therapy or standard of care exists.
Have refused standard therapy
Progressed, or been intolerant to, at least one standard treatment regimen, except for subjects in 1st line cohorts.
PHASE I COMPONENT: Histologic confirmation of relapsed/refractory solid tumors, including tumors of the central nervous system that have failed to respond to standard therapy, progressed despite standard therapy, or for which standard therapy does not exist; patients with diffuse pontine glioma are not required to have histologic confirmation of disease, and are eligible with radiologic confirmation
Failure to respond to or refractory to approved/standard therapy; or for whom standard therapy does not exist, or is not tolerable; or for whom approved/standard therapy is not considered to be sufficient or appropriate by the Investigator.
PROCUREMENT: Cancer is:\r\n* Recurrent or persistent after standard therapy OR\r\n* Patient is unable to receive standard therapy
TREATMENT: Cancer is:\r\n* Recurrent or persistent after standard therapy OR\r\n* Patient is unable to receive standard therapy
Patients with a recurrent/metastatic or refractory solid tumor that has progressed or did not respond to standard therapy, or for which no standard anticancer therapy exists or is too toxic
For initial VSTs and subsequent infusions: patients will be eligible following any type of allogeneic transplant if they have CMV, adenovirus, EBV, BK virus and/or HHV6 infection/disease persistent or recurrent despite 14 days of standard therapy OR after failure of treatment after 7 days of standard therapy OR if unable to tolerate standard therapy; patients with persistent human polymavirus type II (JC) virus infection will be eligible as well
Have histologic or cytological proof of advanced cancer that has progressed and for which there is no further standard anticancer therapy available in the opinion of the investigator.
Failure to respond to standard therapy (usually combination chemotherapy with or without radiation and surgery) or development of progressive disease at any phase of standard therapy (any new lesion or an increase in size > 25% of a pre-existing lesion); patients may enter this study with or without re-induction therapy for recurrent tumor
Additional inclusion for part A: Has a histological confirmation of a solid malignancy (other than HCC) that is refractory to standard therapy or for which no standard of care regimen currently exists.
Patients will undergo standard pre-transplant work-up as dictated by standard practice guidelines the results of which may be used for screening for this study
Stage IIB-IV mycosis fungoides or Sezary syndrome, who have failed at least 1 standard systemic therapy or are not candidates for standard therapy
Disease that has progressed after standard therapies or for which standard therapy is otherwise unsuitable (example, intolerance).
Patients who refuse standard therapy are excluded from the study
Dose escalation: Patients with accessible tumors and with measurable disease as determined by RECIST 1.1 who have received at least one but no more than three prior lines of treatment for their disease and progressed despite standard treatment or are intolerant of standard treatment, or for whom no standard treatment exists
Dose expansion: Patients with advanced/metastatic solid tumors: head and neck squamous cell carcinoma (HNSCC), melanoma, accessible tumors and visceral tumors (LHC165 combination with PDR001 only). Patients must have measurable disease as determined by RECIST 1.1, and have progressed despite standard treatment or are intolerant to standard treatment, or for whom no standard treatment exists and have received at least one but no more than three prior lines of treatment for their disease.
Patients with confirmed diagnosis of advanced malignancy, whose disease failed to respond to or progressed after standard therapy; they could not tolerate standard therapy; or such measures are not acceptable to the subject.
Patients with histologically or cytologically confirmed, advanced solid tumors which have progressed despite standard therapy or for whom no standard therapy exists.
Must have received or been intolerant to standard therapy.
Patients must have histologically confirmed solid tumors that have progressed on standard therapy known to prolong survival or for which no standard treatment options exist
Patients must have histologically confirmed solid tumors that have progressed on standard therapy known to prolong survival or for which no standard treatment options exist
Patient must have non-resectable disease that has progressed following standard therapy or has not adequately responded to standard therapy, or the patient must be intolerant to or have declined available standard therapies, or there must be no accepted standard therapy for their disease.
TUMOR BIOPSY SEQUENCING: Patients with histologically documented solid tumors whose disease has progressed following at least one line of standard therapy and/or no standard of treatment exists that has been shown to prolong survival
TREATMENT: Patients with histologically documented solid tumors whose disease has progressed following at least one line of standard therapy or for which no standard therapy exists that has been shown to prolong survival
Subjects must be diagnosed with a glioma, cholangiocarcinoma or other solid malignant tumor that has progressed despite standard therapy, or for which no effective standard therapy exists, with biopsy-confirmed evidence of an IDH1 or IDH2 mutation associated with neomorphic activity of the encoded proteins
Advanced or metastatic cancer for which no standard therapy exists or that has\n             progressed despite standard therapy
DOSE ESCALATION PHASE: Histological or cytopathological diagnosis of an advanced cancer that is refractory to standard therapy or for which no standard therapy exists
Patients with histologically or cytologically proven advanced solid cancer and have undergone treatment with at least one regimen of standard therapy, either cytotoxic chemotherapy, a molecularly targeted agent, or immunotherapy, or have a form of cancer for which no standard therapy exists; patients with prostate cancer may continue on androgen-deprivation therapy if they are currently receiving it
Locally recurrent or metastatic disease that has progressed on or following standard treatment, or is not a candidate for standard treatment
During dose escalation, subjects with advanced solid tumors (except for primary CNS metastases) that have progressed following at least one standard regimen
Histologically or cytologically proven metastatic or locally advanced tumors for which no standard therapy exists, or where standard therapy has failed, or in patients otherwise ineligible for standard therapy, or for an indication that anti-programmed cell death protein 1 (PD-1) therapy has been shown to be effective in studies in HIV-uninfected participants; disease-specific criteria will be applied for certain common cancers and cancers strongly associated with HIV; however, enrollment will not be confined to these tumors
Subjects must have received and have progressed, or are refractory to standard regimens
Phase I only: any (or no) prior therapy for metastatic disease is allowed, including cetuximab; if a patient has not received prior standard therapy, s/he must have been offered and refused prior standard therapy
Subjects who have progressed or have been intolerant to any standard treatment regimen or refused standard treatment, or for which adequate standard therapy does not exist.
Patient must have received at least 1 prior standard therapy for their disease
Subjects who have progressed on (or not been able to tolerate) standard anticancer therapy or for whom no standard anticancer therapy exists. Must have disease that is objectively measurable
Group 2: BRAFV600 positive metastatic colorectal carcinoma (CRC), or advanced non-small cell lung carcinoma (NSCLC) after failure of at least two lines of prior standard therapy or for whom no further standard therapy is indicated.
Histologically or cytologically confirmed advanced solid tumors (excluding HCC) that have progressed following standard therapy, or for which no standard therapy exists (including surgery or radiation therapy) or participants with RR-DTC.
Refractory to or intolerant of standard therapy
Standard treatment interrupted, except if anti-HER2 therapy
Has stable, or no evidence of, extracranial disease and not receiving systemic therapy for extracranial disease; Note: patients with stable disease must have already received standard therapy or are intolerant to standard therapy
Patients with advanced/metastatic cancer, with measurable disease as determined by RECIST version 1.1, who have progressed despite standard therapy or are intolerant to SOC, or for whom no standard therapy exists. Patients must fit into one of the following groups: • CRC •NSCLC • TNBC• RCC
Has progressed after prior therapy and there is no further effective standard anticancer therapy available (including subject refuses or is intolerant)
Participants must have relapsed disease despite standard therapy
Diagnosis of advanced or recurrent, histologically or cytologically confirmed, solid malignancy that is either metastatic or unresectable. At time of enrollment, subjects either refuse standard curative or palliative therapy, are not candidates for standard curative or palliative therapy, have a disease for which no non-investigational therapy exists, OR have progressed on prior therapy (up to three lines of prior cytotoxic agents are permitted).
Patients must have received standard therapy (or generally accepted upfront therapy if no standard exists) and have no known curative therapy
Have histological or cytological diagnosis of locally advanced/metastatic HER2 solid tumors that has progressed or become intolerant to standard therapy or for which no standard therapy is available
Patient with histologically-confirmed Stage IV malignant metastatic adenocarcinoma of the pancreas; (a) who has relapsed from or is refractory to standard therapy and for whom no therapy exists that would be curative or might provide significant benefit or (b) who are intolerant to or refuse standard chemotherapy and, therefore, for whom experimental therapy is a reasonable option.
Must have received and have progressed, are refractory, or are intolerant to standard therapy appropriate for the specific tumor type. Subjects should not have received more than 5 prior lines of therapy for recurrent or metastatic disease including both standards of care and investigational therapies
Subjects must have histologically or cytologically confirmed, IDH1 gene-mutated advanced solid tumors, including glioma, that have recurred or progressed following standard therapy, or that have not responded to standard therapy.
Patient has a confirmed solid tumor diagnosis according to the following: a. Phase 1: patient has a recurrent or refractory solid tumor that has progressed or did not respond to standard therapy, or for which no standard anticancer therapy exists b. Phase 2: patient has radiologically documented measurable disease by RECIST 1.1 (for neuroblastoma, evaluable disease by MIBG/Curie score is also acceptable) in one of the following tumor types and has failed up to three lines of treatment i. Group 1: neuroblastoma ii. Group 2: rhabdomyosarcoma iii. Group 3: Ewing's sarcoma Phase 1 portion or in preclinical studies
Part A1 only: Patients with histological or cytological diagnosis of HNSCC, HCC, melanoma, or clear cell RCC who progressed on or are intolerant to standard therapy, for which no standard therapy is available or who decline standard therapy.
Patients must have histologically documented solid tumors whose disease has progressed on standard therapy that is known to be associated with a survival advantage or have disease for which there is no known standard therapy
Patient has advanced solid malignancy that has progressed despite standard therapy, or for which no effective standard therapy exists
Failure to respond to standard therapy, or for whom standard therapy does not exist.
The participant has a histologic or cytologic diagnosis of a solid tumor (non-prostate, non-breast) that is metastatic and is refractory to or progressed (or relapsed) following standard therapies, or has disease for which no standard therapy exists; presence of metastatic bone lesion(s) is required
Progressed or not tolerated standard therapy, and no further standard therapy is available
Show objective disease progression after the last administration of the last standard therapy or have stopped standard therapy due to intolerability (excluding ASPS subjects who have not received prior therapy) within 6 months of enrollment.
Patients must have a histologically-confirmed metastatic or locally advanced cancer that has failed to respond to standard therapy, progressed despite standard therapy, or for which standard therapy that increases survival by at least three months does not exist
In investigators opinion, no curative standard therapy exists
Histological or cytological diagnosis of advanced/metastatic solid tumor malignancy. Dose Finding Cohorts: Tumor types will be limited to CRC, SCCHN, squamous NSCLC, bladder, or ovarian carcinomas which have progressed on standard therapy, or for which no standard therapy is available.
Part 1: Subjects with solid tumors that are refractory to, relapsed after or intolerant to standard therapy, or for whom no standard therapy exists or who are considered by the investigator to be inappropriate for standard therapy.
Tumor progression following at least one prior standard therapy
Patients for whom no standard curable therapy exists
Advanced or metastatic solid tumor that has progressed or was not responsive to standard therapy
Phase I: Patients with advanced/metastatic solid tumors, with measurable or non-measurable disease as determined by modified RECIST version 1.1 who have progressed despite standard therapy or be intolerant of standard therapy, or for whom no standard therapy exists, who have tumors harboring one of the following: confirmed PIK3CA mutation or amplification, PTEN loss of function, EGFR mutation, cMET activation and/or HER2 overexpression. Endometrial carcinoma will not be selected for any molecular status.
Phase II: Patients with advanced/metastatic solid tumors, with at least one measurable lesion as determined by modified RECIST version 1.1, who progressed despite standard therapy or be intolerant of standard therapy, or for whom no standard therapy exists, fitting in one of the following groups: Group 1: patients with PIK3CA mutated or amplified ER positive (ER+) breast cancer ; Group 2: patients with endometrial carcinoma (not selected for any molecular status); Group 3: patients with solid tumors (with the exception of PIK3CA mutant/amplified ER+ breast cancer and endometrial carcinoma) harboring PIK3CA mutation or amplification/any PTEN status; Group 4: patients with solid tumors (with the exception of endometrial carcinoma) harboring PTEN loss of function/ PIK3CA wild type; Group 5: non-small cell lung cancer harboring cMET activation and/or EGFR mutation. Up to 3 lines of chemotherapy allowed in advanced/metastatic setting.
Patients with locally advanced or metastatic solid tumors who have either relapsed following, or progressed through, standard therapy; have a current disease state for which there is no standard effective therapy; is not a candidate for, or is unwilling to undergo, standard therapy in cases where no curative option exists.
Advanced malignancy, metastatic or unresectable, that has recurred or progressed following standard therapy or failed standard therapy; or for which no standard therapy currently exists, or for which subject is not a candidate for, or is unwilling to undergo, standard therapy.
Pathologically confirmed advanced G/GEJ/E adenocarcinoma (Cohort 1) or other solid tumor (Cohort 2) for which subject has received prior therapy for advanced disease, for which no standard therapy exists, or subject refuses standard therapy
Patients must have either progressed on least one standard therapy or there must be no standard treatment exists that has been shown to prolong survival for the patient’s disease; patients may have received any number of prior cytotoxic agents
Subjects must have confirmed advanced solid tumor and have progressed, are refractory, or are intolerant to standard therapy appropriate for tumor type. Subjects should not have received more than 3 prior lines of therapy for recurrent or metastatic disease including both standards of care and investigational therapies.
Diagnosis of teratoma for which no additional standard surgical or medical therapy exists
progressed or recurred despite standard therapy
no standard therapy exists
patient is intolerant of standard therapy
At least two-weeks since receipt of prior standard or investigational therapy
Patients must have histologically or cytologically confirmed solid malignancy that is metastatic or unresectable, for which standard curative measures do not exist, that has progressed on at least one line of standard therapy or for which no standard therapies exists
All patients must have received prior first line standard therapy or declined standard therapy, and have been either non-responders (progressive disease) or have recurred
Histologically or cytologically confirmed advanced solid tumor, including glioma, or angioimmunoblastic T-cell lymphoma (AITL) that has recurred or progressed following standard therapy, or that has not responded to standard therapy
Histological or cytological diagnosis of advanced/metastatic solid tumor malignancy which has progressed on standard therapy or for which no standard therapy is available.
Histologically- or cytologically-confirmed melanoma or clear-cell RCC that are refractory to standard therapy or for which no standard therapy exists
Histologically or cytologically confirmed gastrointestinal (GI) carcinoma, which has progressed on standard therapies (surgery, radiotherapy, endocrine therapy, chemotherapy), for which effective therapy is not available or for which patients are not a candidate for or intolerant of such therapies.
Patients must have histologic or cytologic evidence of a solid neoplasm for which no standard therapy is available, or have progressed despite standard therapy, or are intolerant to standard therapy.
Progressed or refractory to at least 1 prior line of standard therapy
Patients with cytopathologically or histopathologically confirmed diagnosis of an advanced solid tumor which has progressed despite standard therapy, or for which no standard therapy exists or patients with locally advanced or metastatic basal cell carcinoma who are not amendable or eligible for standard therapy.
Advanced malignant solid tumors for which no curative therapy exists that has recurred or pgrogressed following standard therapy
Progressed, or been intolerant to, at least one standard treatment regimen
Tumors that are relapsed or refractory to at least 1 prior anti-cancer systemic therapy and for which no standard therapy exists
Patients must have histologically or cytologically confirmed advanced malignant solid tumor that has recurred or progressed following standard therapy, or that has not responded to standard therapy, or for which there is no standard therapy, or who are not candidates for standard therapy
RCC patients only: Tumor progression after receiving standard/approved chemotherapy and/or targeted agent, where there is no approved therapy or for tumors where sorafenib based therapy would be standard therapy (Phase I)
Diagnosed with a locally advanced or metastatic malignancy that has progressed despite standard therapy, or for which no effective standard therapy exists. Only patients with tumors characterized by genetic abnormalities in ALK were enrolled.
Diagnosed with advanced refractory solid malignancies or intolerant of standard therapy for the stage of the disease (because there is currently no standard approved therapy for adenoid cystic carcinoma, therefore there is no requirement of prior therapy for this patient population)
Dose-escalation stage: Participants with histologically documented incurable, locally advanced, or metastatic epithelial malignancy that has progressed despite standard therapy or for which no standard therapy exists
Expansion stage: Participants with one of the following epithelial, histologically-documented, incurable, locally advanced, or metastatic tumor that has progressed despite standard therapy or for which no standard therapy exists: CRC, NSCLC, HNSCC, or pancreatic cancer
Disease that has progressed after standard therapy for the specific tumor type, or for which standard therapy has proven to be ineffective, intolerable, or is considered inappropriate, or if no further standard therapy exists; exceptions: NSCLC, head and neck squamous cell cancer (HNSCC), bladder cancer, MSI-H/dMMR cancers and melanoma expansion cohorts in Part 2B pembrolizumab combination. 1) Subjects must not have received more than 5 prior lines of therapy for advanced disease including both standards of care and investigational therapies. 2) Subjects who received prior anti-Programmed cell death protein 1(PD-1)/ Ligand-1 (L1) therapy must have received at least 4 months of treatment (Part 1B and Part 2B).
Phase I-Ib part (including dose ranging part): Patients with advanced/metastatic solid tumors, with measurable or non-measurable disease as determined by RECIST v1.1, who have progressed despite standard therapy or are intolerant of standard therapy, or for whom no standard therapy exists and who did not receive prior anti-PD-1/PD-L1 treatment.
Phase II part (MBG453 single agent): Patients with advanced/metastatic solid tumors in the indication in which at least one confirmed PR or CR was seen during the dose escalation phase I part. Patients must have measurable disease as determined by RECIST v1.1, have progressed despite standard therapy or be intolerant to standard therapy.
Phase II part (MBG453 in combination PDR001): Patients with advanced/metastatic tumors in the below selected indications, with at least one measurable lesion as determined by RECIST v1.1, who have received standard therapy and are intolerant of standard therapy or have progressed following their last prior therapy.:
Has progressed after prior therapy and either a) there is no further effective standard anticancer therapy available (including subject refusal) or b) is intolerant to standard anticancer therapy.
Histologically confirmed advanced malignancy defined as any of the following tumors for which no further standard or curative therapy exists or is considered appropriate by the Investigator:
Participants with hepatocellular carcinoma or Intrahepatic Cholangiocarcinoma (ICC) who have progressed despite standard therapy or are intolerant of standard therapy
Confirmed locally advanced and/or metastatic solid tumor in participants who have progressed on a standard therapy, are intolerant to standard therapy, and/or are non-amenable to standard therapy
Patients with a histologically/cytologically confirmed diagnosis of advanced disease of any of the following tumors that progressed to standard therapy or for whom no standard therapy exists:
Must have received and progressed on or failed one standard/approved treatment for cancer type, if available
Histologically- or cytologically-confirmed diagnosis of locally advanced or metastatic solid tumor that harbors an NTRK1/2/3, ROS1, or ALK gene rearrangement
Phase 1 ONLY: histologically or cytologically confirmed advanced/metastatic solid tumors for which carboplatin/etoposide treatment is considered appropriate.
In dose escalation (Phase I), patients must have histologically or cytologically confirmed metastatic disease from any solid tumor that is incurable and fulfills one of the following criteria:\r\n* Has demonstrated progression of disease following at least one line of effective systemic therapy; prior treatment with anti-CTLA-4 antibody (including ipilimumab) is allowable OR\r\n* For which effective therapy does not exist
Histologically or cytologically confirmed diagnosis of locally advanced or metastatic solid tumor (including non-Hodgkin Lymphoma) (Stage IV, AJCC v.7) that harbors an ALK, ROS1, NTRK1, NTRK2, or NTRK3 gene rearrangement by protocol specified tests.
Participants must have histologically or cytologically confirmed disease from any solid tumor
Histologically or cytologically documented, injectable cancer lesion (limited to solid tumors and mycosis fungoides)
Participants must have histologically or cytologically confirmed disease from any solid tumor
Part A and Part B: Has histologically or cytologically-confirmed metastatic solid tumor.
Histologically or cytologically confirmed advanced solid tumors including:
Has a histologically- or cytologically-confirmed advanced/metastatic solid tumor by pathology report and have received, or been intolerant to, or been ineligible for all treatment known to confer clinical benefit. Participants with solid tumors of any type are eligible for enrollment.
Patients with a histologically or cytologically confirmed solid tumor malignancy
Has a histologically- or cytologically-confirmed advanced/metastatic solid tumor or lymphoma by pathology report and who has received, or been intolerant to, all treatment known to confer clinical benefit. Solid tumors and lymphomas of any type are eligible for enrollment.
Histologically or cytologically-documented, advanced solid tumor of one of the following types:
For enrollment into the NTRK cohort: participants must have a histologically or cytologically confirmed advanced solid tumor and must have received at least one prior line of therapy in the metastatic setting
Diagnosed with histologically confirmed solid tumor located in the peripheral lung
Have histologically or cytologically confirmed diagnosis of advanced solid tumor cancer (excluding lymphomas) for which there is no further standard therapy or when standard therapy is contraindicated. Patients with HGG must have shown unequivocal evidence for recurrence or progression by MRI scan or must have histologically proven tumor recurrence.
Histologically or cytologically confirmed diagnosis of an advanced, malignant, solid tumor(s) with all standard treatment options having been exhausted or declined.
Patients with other immune checkpoint naïve histologically/ cytologically confirmed advanced solid tumor type that has received and progressed on standard-of-care therapy(ies).
Histologically or cytologically confirmed diagnosis of advanced disease of any of the following tumor types:
Histologically/cytologically confirmed advanced/metastatic or unresectable solid tumors, no treatment options
PHASE I: Histologically confirmed solid tumor malignancy
Have a histologically confirmed advanced solid tumor for which curative treatment is not available
Histologically or cytologically confirmed diagnosis of selected advanced or metastatic solid tumors.
Histologically confirmed advanced refractory solid tumor that is measurable or evaluable per RECIST 1.1 criteria.
Histologically or cytologically confirmed solid tumor cancer
Patients must have histologically or cytologically confirmed solid organ malignancy
Patients must have histologically or cytologically confirmed progressive advanced or metastatic solid tumor of one of the following:
Has a histologically or cytologically confirmed diagnosis of a solid tumor malignancy (except for any excluded malignancies listed in the Exclusion Criteria) that is not responsive to standard therapy(ies) or for which there is no approved therapy.
Patients must have histologically (or cytologically)-confirmed diagnosis of solid tumor, refractory after standard therapy for the disease or for which conventional systemic therapy is not reliably effective or no effective therapy is available.
Solid tumor specific:\r\n* Patients must have a histologically/cytologically confirmed primary solid tumor\r\n* Radiographic or clinical evidence of advanced/metastatic disease that is resistant to standard therapy or for which no standard therapy is available; lesions may be measurable or non-measurable
Have a histologically confirmed advanced solid tumor for which curative treatment is not available
Histologically confirmed malignant extra-cranial solid tumor or desmoid fibromatosis.
Patients with a histologically-confirmed, advanced solid malignancy for which pembrolizumab is approved (Parts C and D)
Histologically or cytologically confirmed advanced solid tumor malignancy, refractory or relapsed from prior therapy, or for whom no alternative therapy is available
Histologically or cytologically confirmed diagnosis of solid malignant tumor.
Patients with histologically or cytologically confirmed diagnosis of refractory metastatic solid tumor for whom no other standard treatment options are available
Arm 1: histologically or cytologically confirmed solid tumors that are advanced that gemcitabine-based treatment is considered a clinically appropriate option
Arm 3: histologically or cytologically confirmed solid tumors that are advanced that gemcitabine plus cisplatin treatment is considered a clinically appropriate option
Phase Ib: Patient must have histologically or cytologically documented solid tumor malignancies
Part 1a: Subjects with histologically or cytologically confirmed advanced or metastatic solid tumors that have failed prior standard therapy (including subject refusal or intolerance).
(Combination Therapy - Part E and Part F) -- Histologically or cytologically confirmed advanced or metastatic solid malignancy for which pembrolizumab treatment is approved. In Part F, other advanced solid tumor indications may be eligible as identified by the Sponsor.
Histologically confirmed malignant solid tumor and not a candidate for known regimens or protocol treatments of higher efficacy or priority
Histologically or cytologically confirmed diagnosis of advanced cancer in patients with solid tumors that are refractory to standard treatment, or for whom no effective therapy exists.
Histologically or cytologically confirmed solid tumors or hepatocellular carcinoma with known disease progression.
Histologically confirmed advanced solid tumors with measurable lesions per RECIST v1.1 that are considered nonamenable to surgery or other curative treatments or procedures.
Patients with histologically or cytologically confirmed diagnosis of locally advanced or metastatic solid tumor disease for which standard therapy is not effective, available, acceptable, or is intolerable.
ARM B: Histologically or cytologically confirmed solid tumor with subcutaneous/cutaneous lesions that is refractory (RECIST or with unequivocal clinical progression of disease) to or intolerant to standard therapy
Patients must have histologically and/or cytologically confirmed solid tumors or B cell lymphoma that are metastatic or unresectable and for which standard treatment options do not exist; patients with hepatocellular carcinoma are eligible without pathological diagnosis if diagnosed on the basis of blood work and imaging
Histologically confirmed solid tumor (leukemia and lymphoma are excluded)
Histologically- or cytologically- confirmed solid tumor (except melanoma) that is\n             metastatic or unresectable
Histologically or cytologically confirmed diagnosis of malignancy with demonstrated progression of a solid tumor (non-lymphoma) with no alternative standard-of-care therapeutic option (certain exceptions may apply).
For the phase I portion, patients must have histologically and/or cytologically confirmed malignant solid tumor that is refractory to standard therapies
Subjects with histologically or cytologically confirmed advanced solid tumors or lymphoma that is metastatic or unresectable, and for whom standard life-prolonging measures are not available. Specific tumor types that will be selected for study in Phase 2 are detailed in the protocol.
Part 1: Subjects with histologically or cytologically confirmed advanced or metastatic solid tumors that have failed prior standard therapy (disease progression; subject refusal or intolerance is also allowable).
Subject must have histologically or cytologically confirmed solid tumor;
Subjects must have histologically or cytologically confirmed advanced solid tumor for recurrent or metastatic disease.
Histologically or cytologically documented, incurable or metastatic solid tumor or hematologic malignancy that is advanced (non-resectable) or recurrent and progressing since the last anti-tumor therapy and for which no recognized standard curative therapy exists
Men and women, 18 years or older, with histologically or cytologically-confirmed, advanced solid tumors, Non-Hodgkin Lymphona (NHL), Multiple Myloma (MM), or advanced unresectable solid tumors limited to the tumor types below.
For Phase 1, subjects with histologically or cytologically confirmed advanced or metastatic solid tumors that have failed prior standard therapy (disease progression; subject intolerance is also allowable).
Part A only: Histologically or cytologically confirmed metastatic and/or advanced solid tumors with documented progressive disease for whom no further standard therapy is indicated.
Subjects must have a histologically or cytologically confirmed advanced or metastatic tumor for which no effective standard therapy is available.
Diagnosis of histologically or cytologically confirmed, advanced solid tumor malignancy that is refractory to or not a candidate for standard therapy
Histologically or cytologically confirmed diagnosis of selected advanced or metastatic solid tumors.
Patients with histologically or cytologically confirmed solid malignancy are eligible for treatment as long as insurance approval for docetaxel is obtained
A histologically confirmed solid tumor of the gastrointestinal tract including
In the dose-expansion phase: histologically- or cytologically- confirmed advanced solid tumor where if an approved first-line therapy is available, subjects must have failed, be intolerant to, be ineligible for, or have refused
Phase Ia: Patients must have histologically or cytologically documented metastatic solid tumor malignancies
Presumptive or histologically confirmed advanced or metastatic non-curable solid tumor (if limited to a single lesion, and may not be a candidate for curative surgery or radiation therapy).
Patients must have a histologically or cytologically confirmed metastatic solid tumor malignancy for the phase I component; the phase II component will require patients to have histologically or cytologically confirmed non-small cell lung carcinoma regardless of histology
Subjects with advanced, histologically or cytologically confirmed solid tumors described to express fibroblast growth factor receptor 2 (FGFR2) that are refractory to any standard therapy
Subjects with a histologically or cytologically confirmed diagnosis of solid tumors, advanced or metastatic, refractory to or relapsed from standard therapies or for which there is no known effective treatment
For Part 1a: Subjects with histologically or cytologically confirmed advanced or metastatic solid tumors that have failed prior standard therapy (including subject refusal or intolerance).
Histologically or cytologically confirmed diagnosis of solid malignancy, for which no standard curative or life prolonging therapy is available.
Treatment Group A (TGA): Part 1 and Part 2: Any advanced solid tumor or lymphoma; Part 3: Histologically confirmed disease in specific solid tumors and lymphomas
Histologically or cytologically confirmed solid tumor.
Histologically or cytologically confirmed advanced solid tumor with no available standard treatment options in the opinion of the investigator.
Part A Subjects with histologically or cytologically confirmed malignant advanced solid tumors, who have progressed on at least 1 prior chemotherapy, and for whom either
Subject had histologically or cytologically confirmed diagnosis of advanced solid tumor (measurable or nonmeasurable disease) for which no standard therapy is available.
Must have a histologically or cytologically confirmed metastatic or locally advanced and incurable solid tumor that is deemed appropriate for treatment with 1 of the 2 chemotherapy regimens in Part B of this study, or have progressed despite standard therapy, or for whom conventional therapy is not considered effective. The tumor must be radiographically or clinically evaluable or measurable.
Histologically or cytologically confirmed diagnosis of solid tumor malignancy that is not responsive to standard therapies or for which there is no approved or curative therapy.
Have a histologically or cytologically confirmed diagnosis of advanced solid tumor or lymphoma, or primitive hepatocarcinoma with radiological diagnosis
Histologically or cytologically confirmed diagnosis of a solid tumor.
Dose escalation phase: Subjects with histologically or cytologically confirmed advanced malignancies (solid tumors and malignant lymphomas) who were refractory to or had exhausted all available therapies. Subjects had to have evaluable or measurable disease (as per RECIST 1.1 or Cheson 2007 criteria).
Patients must have a histologically or cytologically confirmed metastatic or locally advanced and incurable solid tumor that is felt to be appropriate for treatment with 1 of the 3 chemotherapy regimens in this study, or have progressed despite standard therapy, or for whom conventional therapy is not considered effective. The tumor must be radiographically or clinically evaluable and/or measurable
Histologically or cytologically confirmed diagnosis of a solid tumor for which no further effective standard treatment is available. Patients with lymphomas may be enrolled.
Histologically or cytologically confirmed diagnosis of solid tumor in advanced stage which taxane-based therapy is a rational treatment option.
Patients aged ?18 years with a histologically or cytologically confirmed diagnosis of a solid tumor or lymphoma for which no further effective standard treatment is available
Patients with a histologically and/or cytologically confirmed solid tumor who are resistant / refractory to approved therapies or for whom no curative therapies are available
Histologically or cytologically confirmed diagnosis of solid malignancy
(Part 1 only) Have a histologically/cytologically confirmed diagnosis of advanced solid tumor, including sarcoma that is refractory to standard therapy. (Part 2 only) Have a histologically confirmed diagnosis of advanced, unresectable, or metastatic soft tissue sarcoma not amenable to curative treatment with surgery or radiotherapy.
Histologically or cytologically confirmed advanced solid tumor with no available standard treatment options in the opinion of the Investigator
Histologically or cytologically confirmed advanced solid tumor with no available standard approved treatment options in the opinion of the Investigator
Histologically or cytologically confirmed cancer (hematologic or solid) who are not currently on hospice care
Patients with a histologically or cytologically confirmed solid tumor or aggressive NHL who are refractory to or have exhausted all available therapies
For Part 1: Histologically- or cytologically-confirmed diagnosis of unresectable GIST or another advanced solid tumor. Patients with unresectable GIST must have disease that has progressed following imatinib and at least 1 of the following: sunitinib, regorafenib, sorafenib, dasatinib, pazopanib or an experimental kinase-inhibitor agent, or disease with a D842 mutation in the PDGFR? gene. Patients with an advanced solid tumor other than GIST must have relapsed or refractory disease without an available effective therapy. OR For Part 2:
Participants must have histologically or cytologically confirmed diagnosis of solid tumor malignancy, lymphoma, or multiple myeloma
Participants must have histologically confirmed diagnosis of a solid tumor for which no curative therapy exists
For Parts A and B: Has histologically or cytologically confirmed metastatic solid tumor
Somatostatin receptor 2 positive tumor as assessed at pre-screening or within 180 d of first drug administration using indium SPECT or gallium PET Patients in Phase 1 must have a histologically or cytologically-confirmed solid tumor in 1 of the following categories:
For patients enrolling once escalation is complete, disease must be measurable per RECIST 1.1 criteria with last imaging performed within 28 days prior to first drug dose In addition to the criterion listed above, Patients in Phase 2a must have a histologically- or cytologically-confirmed, advanced or metastatic solid tumor, in 1 of the following categories: disease history specificied in one of the criteria listed below:
Participants must have a histologically or cytologically confirmed metastatic or locally advanced solid tumor(s) appropriate for treatment with one of the 2 combination therapies in Part B of this study, have progressed despite standard therapy, or for whom conventional therapy is not considered effective.
Adult participants who have a histologically or cytologically confirmed metastatic or locally advanced solid tumor that is appropriate for treatment with either docetaxel or carboplatin + paclitaxel in Part B of this study, or have progressed despite standard therapy, or for whom conventional therapy is not considered effective. The tumor must be radiographically or clinically evaluable and/or measurable.
Patients with a histologically confirmed solid tumor:
Have non-epithelial ovarian tumors (e.g., germ cell tumors, sex cord stromal tumors)
Patients with unbiopsied diffuse intrinsic pontine tumors will NOT be eligible for this study.
Patients that do not qualify for one of the histologic cohorts may be considered for registration in the “Not Otherwise Categorized” Rare Tumors cohort with confirmation of at least one of the study chairs via email
Clinical T4 tumors
Tumors must have PD-L1 status tested centrally as part of the ALCHEMIST-SCREEN protocol
Histologically proven stage III colon adenocarcinoma (any T [Tx, T1, T2, T3, or T4], N1-2M0; includes N1C); tumors must be deemed to originate in the colon including tumors that extend into/involve the small bowel (e.g. those at the ileocecal valve)
Patients with grade 1 NRSTS tumors of any size are not eligible
Patients with MYCN amplified tumors are not eligible
Patients must have had all grossly visible papillary tumors removed within 30 days prior to registration or cystoscopy confirming no grossly visible papillary tumors within 30 days prior to registration
Ewing's family of tumors (EFTs)
For Phase 1b, must have advanced refractory solid tumors in any line of therapy.
Phase II part: Patients with advanced/metastatic solid tumors, with at least one measurable lesion as determined by RECIST version 1.1, who have progressed following their last prior therapy, and fit into one of the following groups:
Rare Tumors:
COHORT A: Patients with newly diagnosed, previously untreated primary tumors that present with brain metastases should not forego available therapy that has demonstrated a definitive overall survival benefit as first line therapy for metastatic disease; therefore, in cases of previously untreated systemic solid tumors only those patients for whom there is no available therapy with definitive overall survival benefit, those that have failed at least one line of prior therapy for their primary tumor, or those refusing standard therapy will be eligible for this study; specifically, for patients with previously untreated primary tumors, the following diagnoses will be excluded: HER2-positive breast cancer; small cell lung cancer; non-small cell lung carcinoma (NSCLC) with targetable genomic tumor aberrations (e.g. EGFR, ALK)
Carcinoid tumors of any site are eligible; patients with pancreatic neuroendocrine tumors are excluded
Patients with histologically or serologically confirmed relapsed/refractory nonseminoma germ cell tumor, (i.e., embryonal carcinoma, choriocarcinoma, or yolk sac tumors) including female germ cell tumors (GCT) and primary mediastinal NSGCT
Any solid tumors with masses that are accessible without imaging
Subjects with any of the following tumors who have experienced relapse following front-line therapy, or who are refractory to front-line therapy, and subjects with tumors that carry a poor prognosis and have no known standard curative therapy are eligible;\r\n* Brain tumors of all World Health Organization (WHO) grades except diffuse intrinsic pontine glioma (DIPG); patients with DIPG are not eligible\r\n* Extracranial solid tumors including histiocytoses (e.g. Langerhans cell histiocytosis [LCH], juvenile xanthogranuloma [JXG], histiocytic sarcoma)
Prior consent to have tumors used for unspecified future research
Subjects must have measurable disease by RECIST 1.1 criteria including one target tumor for injection. Superficial tumors must have one tumor greater than or equal to 1.0 cm, deep tumors greater than or equal to 1.0 cm (as measured by caliper (for non-injected tumors only) or image guidance);
Subjects must have a minimum of one injectable lesion as determined by the investigator (for superficial tumors) or radiologist (deep tumors).
Tumors whose proximal end are higher that the level of the carina
Cumulative volume of all tumors ? 15 cc
Neuronal tumors \r\n* Ganglioglioma (excluding tumors with anaplastic astrocytic components) \r\n* Infantile desmoplastic ganglioglioma
Patients with subependymal giant cell astrocytomas are excluded; patients with intrinsic brain stem tumors of the pons will be excluded from the study
Endometrial Carcinoma (sarcomas and mesenchymal tumors are excluded)
Salivary Gland Carcinoma (sarcomas and mesenchymal tumors are excluded)
Advanced solid tumors
At least one site of measurable disease in subjects with solid tumors and NHL.
High grade, rapidly proliferative solid tumors (eg, small cell lung cancer, germ cell tumors, neuroblastoma) with extensive tumor burden.
Patients with low grade gliomas and Rb1 negative tumors
Patients with sessile appearing tumors, which may be invasive or high-grade
In addition to having AR+ tumors, patients must fit into 1 of the 2 following categories:
Both peripheral and central tumors are accepted for this trial
IO therapy resistant or insensitive tumors
Necrotic tumors or tumors close to large blood vessels that may impose an increased bleeding risk when treated with anti-VEGF agents.
Infratentorial tumors
T1 to T2a tumors OR T3 tumors smaller than 7 cm invading the mediastinal or pericardial pleura are also eligible for this protocol as long as normal tissue dose constraints can be met
Regimen A only (monotherapy): Subjects with advanced metastatic solid tumors
Phase 2a: Patients with various solid tumors or NHL who have received prior therapy.
Advanced solid tumors
Have Karnofsky score ?40 at enrollment (not applicable for subjects with benign bone tumors)
Phase 1: Participants must be diagnosed with histologically confirmed solid tumors (excluding CNS tumors), which is relapsed or refractory, and for which there are no currently available therapies.
Patients with secreting tumors must be receiving pharmacologic catecholamine blockade
T4 tumors with involvement of any adjacent structure, including the trachea, aorta or pleura
Patients with tumors that cannot be measured or clinically followed
Patients with tumors > 7 cm or tumors involving the main bronchus or associated vessels or tumors that invade any critical structures (such as esophagus, brachial plexus, heart, mediastinal major vessels) are not suitable for SABR
Patients with neoplastic lesions in the brainstem, cerebellum, or spinal cord, tumors extending into or crossing the corpus callosum, intraventricular tumors, pineal tumors, pituitary tumors, radiological evidence of active (growing) multifocal disease, leptomeningeal disease, or other locations at the discretion of the treating neurosurgeon
Patients with progression of multifocal tumors or tumors involving the posterior fossa (brainstem and cerebellum) will be excluded, as will patients where the anticipated treatment margin will be within 5 mm of critical intracranial structures (e.g., primary branches of cerebral vessels, dural sinuses, hypophysis or cranial nerves).
For subjects enrolled for “major deformity” or a “significantly disfiguring” tumor, eligible tumors will be limited to tumors of the head & neck or those on other areas of the body that are unable to be concealed by standard garments; in order to enroll a plexiform neurofibroma for these indications, the Study Chair or Co-Chair must be contacted to review patient eligibility prior to enrollment
Accessible tumors for sequential biopsies
Tumors must be potentially surgically resectable via a transoral approach, at the discretion of the treating surgeon
non-hilar tumors
Primary tumors of radiosensitive histology (lymphoma, multiple myeloma, small cell carcinoma, germ cell tumors), as conventional radiation is likely to be effective in such cases
Patients may have single or multinodular tumors
Has measurable disease based on either RECIST 1.1 for solid tumors or RANO for CNS tumors
Patients must have histologically confirmed advanced RCC (any histology); collecting duct tumors and tumors originating from the renal pelvis or upper urinary tract are considered of urothelial origin and are excluded from this protocol
Subjects must have measurable liver tumors that are suitable for injection.
Tumors involving the cerebellum
Only MUC16^ecto tumors with moderate to strong immunoreactive scores (3-5) will be considered positive
Patients whose tumors are positive for the sensitizing ROS-1 fusion
Patients must have untreated or relapsed SCCS that is considered to be aggressive and locally advanced by the following criteria: tumors 2 cm or more, tumors invading deep tissues such as muscle, cartilage or bone; tumors showing perineural invasion, and/or tumors metastatic to loco-regional lymph nodes; patients may have had prior surgical interventions or been treated with investigational agents with residual or recurrent disease
Patients with primary tumors located at or above the carina
Surgery achieves either no gross residual disease or optimal cytoreductive status defined as no single lesion measuring more than 1 cm in its greatest diameter (this protocol calls for the intentional delay in resection of up to 3 tumors per patient until the HIPEC procedure is complete; the surgeon will identify these tumors as easily resectable from a technical and safety aspect)
Patients with tumors primarily of the tail of the pancreas requiring a distal pancreaticoduodenectomy would be excluded; tumors of the body that require a surgical approach similar to pancreatic head tumors are acceptable
Infratentorial and multi-focal tumors are eligible
Tumors infiltrate the cerebellum, bilateral corpus callosum (“butterfly glioma”), ventricular system, or brain stem
Patients must have a confirmed histopathologic diagnosis and be classified as high risk defined by having an expected survival of < 10%; examples include:\r\n* Neuroblastoma or ganglioneuroblastoma\r\n** Failure to achieve at least a partial response (PR) after induction therapy with Children’s Oncology Group (COG) ANBL0532 or standard chemotherapy\r\n** Refractory to induction chemotherapy with COG ANBL0532 or standard chemotherapy\r\n** Patients with high risk disease whose autologous peripheral blood stem cell product is contaminated with neuroblastoma or who do not have an autologous product available\r\n** Patients with high risk disease who do not meet eligibility requirements/organ function requirements for myeloablative conditioning\r\n** Patients with >= 5 identified lesions on the end of induction (COG ANBL0532 or standard chemotherapy) meta-iodobenzylguanidine (MIBG) scan \r\n* Stage 4 rhabdomyosarcoma\r\n* Metastatic Ewing sarcoma\r\n* Osteosarcoma with metastatic disease beyond the lungs and/or with lung metastases not amenable to resection\r\n* Hepatoblastoma not amenable to resection\r\n* Metastatic melanoma\r\n* Desmoplastic small round cell tumor\r\n* Brain tumors such as astrocytic tumors, oligodendroglial tumors, ependymal tumors, choroid plexus tumors, other neuroepithelial tumors, neuronal and mixed neuronal-glial tumors, tumors of the pineal region, embryonic tumors\r\n* Any other solid tumor and soft tissue sarcoma with an estimated < 10% chance of survival will be considered on a case by case basis at the departmental tumor board and/or sarcoma meeting
Biliary strictures caused by confirmed benign tumors
For tumors that are invasive, HER2 must be performed (positive or negative is acceptable).
Patients with advanced malignant hepatic tumors.
Patients with measurable inoperable, histologically confirmed primary lung and esophageal carcinomas, thymic neoplasms, germ cell tumors, malignant pleural mesotheliomas or chest wall sarcomas, as well as patients with gastric, colorectal or renal cancers and sarcomas metastatic to the thorax are eligible
All patients with histologic proof of advanced solid tumors, who are not candidates for known regimens or protocol treatments of higher efficacy or priority
WHO grade I: tumor that are newly diagnosed and tumors that are incompletely excised; tumors that have recurred post resection
Patients must have the diagnosis of (a) DSRCT with peritoneal involvement or (b) other 8H9-positive solid tumors involving the peritoneum (e.g. adrenocortical carcinoma, Wilm's tumor)
For tumors other than DSRCT, 8H9 reactivity must be confirmed by immunohistochemistry
Pure sarcomas or borderline tumors or mucinous tumors
Group 2: NRAS or HRAS mutant solid tumors(Part B)
Patients whose tumors harbor a ROS1 rearrangement must have demonstrated progression on or intolerance to crizotinib
More than 3 metastatic tumors
Subjects must not have tumors adjacent to vital structures such as carotid arteries.
At least two BCC tumors, preferably more; these tumors must be located in different body regions or alternatively, located > 10 cm apart at sites that can be reproducibly separated into red and blue illumination fields
THE PATIENT IS INELIGIBLE TO PARTICIPATE IN PART 2 IF ANY OF THE FOLLOWING OCCUR: Tumors do not engraft in the mice or do not respond to any of the selected agents.
Patients with tumors that score negative in the in vitro organoid bio-assay will be excluded
Patients with non-melanoma skin cancers (NMSC) must have advanced or refractory tumors\r\n* Advanced/unresectable is defined by at least 1 of the following criteria: tumors 2 cm or more, tumors considered unresectable, tumors invading deep tissues such as muscle, cartilage or bone, tumors showing perineural invasion, and/or tumors metastatic to loco-regional lymph nodes and/or distant sites\r\n* Refractory is defined by persistent or recurrent tumor despite prior therapy consisting of at least 1 of the following: surgery, radiation therapy, intralesional therapy, topical therapy, or systemic therapy
Multiple (? 2) separate enhancing tumors
tumors encasing major vascular structures (i.e., carotid artery or tumors close to other vital organs), are not considered appropriate
Tumors in which the invasive component is present only as micro-invasion
Patients with grade 1 non-rhabdomyosarcoma soft tissue sarcomas (NRSTS) tumors of any size are not eligible
Assessment of GD2 status is not required for NB or for other tumors known to express GD2 in 70% or more of cases: specifically osteosarcoma (GD2 expressed in 88%), spindle cell sarcoma (93%) and desmoplastic small round cell tumor (DSRCT) (70%); all other non-NB tumors will require confirmation of GD2 expression on cell surface by immunohistochemistry on fresh frozen tissue that will be performed at MSKCC; patients with suspected GD2-positive tumors (other than osteosarcoma, spindle cell sarcoma or DSRCT) will have their tumors assessed after obtaining a separate informed consent for this purpose
Patients with tumors located outside the ventricles (basal ganglia, thalamus) are not eligible
Patients with histologically confirmed unresectable or metastatic pancreatic (p)NETs of low or intermediate grade; high-grade tumors or tumors with small cell histology will be excluded (Part 2)
Patients with histologically or cytologically proven lung or esophageal cancers, thymic or mediastinal germ cell tumors, malignant pleural mesotheliomas, or primary thoracic sarcomas, as well as patients with sarcomas, melanomas, germ cell tumors, or epithelial malignancies metastatic to the lungs, mediastinum, or pleura that have no clinical evidence of active disease (NED) or minimal residual disease (MRD) not readily accessible by non-invasive biopsy or resection/radiation following standard therapy
Histologically proven malignant solid tumors with measurable disease (except lymphomas)
Tumors must have a Ki-67 index greater than 20% and/or > 20 mitotic figures/10 high-power fields
Patients with advanced malignant solid tumors are excluded
Patients with carcinoid tumors
Selected tumors with rhabdoid features
Other INI1-negative malignant tumors (e.g., dedifferentiated chordoma) with Sponsor approval
Cohort 2 - MRT/RTK/selected tumors with rhabdoid features
Cohort 3 - INI-negative tumors:
Other INI1-negative malignant tumors (e.g., dedifferentiated chordoma) with Sponsor approval
For subjects with INI1-negative tumors only - have the following test results available:
Morphology and immunophenotypic panel consistent with INI1-negative tumors, and
Phase I (Cohort X): Participants with PIK3CA-mutant tumors and measurable disease per RECIST v1.1
Phase 1: Subjects with advanced or metastatic solid tumors.
Patients with bilateral renal tumors are eligible provided both tumors have undergone full surgical resection and at least one of the tumors meets all eligibility criteria; patients must plan to start study drug within 84 days after the date of the resection of the first tumor
Inaccessible tumors or for whom biopsy is contraindicated
Patients with non-adenocarcinomas, adenosquamous carcinomas, islet cell (neuroendocrine) tumors, cystadenomas, cystadenocarcinomas, carcinoid tumors, duodenal carcinomas, distal bile duct, and ampullary carcinomas; patients with tumors that are largely IPMN with a minimal or minor component of invasive carcinoma are not eligible; patients with acinar carcinomas are not eligible; patients with IPMN’s that contain some secondary (minor) foci of adenocarcinoma are also not eligible
Individuals with inaccessible tumors or for whom biopsy is contraindicated
Presence of advanced malignant hepatic tumors.
Prior nasopharyngeal cancer, salivary gland or sinus tumors.
Documented IDH1R132-mutant tumors
Metastatic or inoperable solid tumors* (except gastrointestinal tumors or tumors that originated or metastasized to the liver) for which no standard treatment exists, or have progressed or recurred following prior therapy.
Patients with metastatic malignant solid tumors who received treatment in the past 6 months are excluded
Patients who have uterine sarcomas, carcinosarcomas, serous tumors (any component) or pure clear cell carcinomas.
Any patients with infratentorial tumors
Periampullary tumors
Locally advanced tumors at diagnosis (T4), including tumors fixed to the chest wall, peau d’orange, skin ulcerations/nodules, or clinical inflammatory changes (diffuse brawny cutaneous induration with an erysipeloid)
Tumors involving the cerebellum
Have recurrent or metastatic solid tumors
Tumors with involvement of the mediastinum.
For subjects enrolled for a “major deformity” or “significantly disfiguring” tumor, eligible tumors will be limited to tumors of the head & neck or those on other areas of the body that are unable to be concealed by standard garments; in order to enroll a plexiform neurofibroma for these indications, the study chair or co-chair must be contacted to review subject eligibility prior to enrollment
Patients with advanced malignant solid tumors are excluded
Patients with advanced malignant hepatic tumors (metastasis)
other solid tumors (all comers) for which there is no standard systemic therapy and there is a rationale for use of pexidartinib at the Investigator's discretion
Recurrent or refractory solid tumors
Technically resectable, single tumors of any size, tumors with satellite nodules within 2 cm of the primary tumor that are resectable; limited and resectable multi- focal disease (less than 4 tumors technically resectable)
VS or meningioma surgery determined clinically necessary by the treating physician; similar cerebellopontine (CP) angle schwannomas, such as facial nerve schwannomas and “collision tumors”, i.e. tumors arising from multiple cranial nerves, are eligible
Locally advanced tumors at diagnosis, including tumors fixed to the chest wall, peau d’orange, skin ulcerations/nodules, or clinical inflammatory changes (diffuse brawny cutaneous induration with an erysipeloid edge)
Borderline resectable- Tumors considered borderline resectable are defined as follows:
T0 tumors
Patients with cystoscopically detected bladder tumors requiring TURBT
Patients with bladder tumors which are endoscopically resectable by surgeon’s judgment with only one trip into the operating room
Patients with advanced malignant hepatic tumors
Patients with centrally-located pulmonary or mediastinal primary tumors or metastases adjacent to or invading large blood vessels
Tumors poorly visualized by x-ray mammography or ultrasound imaging
Tumors measuring greater than 20mm in diameter
Cavitary tumors or tumors invading or abutting large blood vessels.
Tumors must be supratentorially located
Patients with advanced malignant hepatic tumors
Concurrent metastatic solid tumors
Patients with primary supraglottic tumors that involve the true larynx
Detectable AR-V7 from circulating tumors (CTCs)
Borderline resectable- Tumors considered borderline resectable are defined as follows:
Metastatic and/or locally advanced malignant solid tumors enriched in tumor types known to be mesothelin expressing
Based on the results of the mutation test, lymphoma subjects may be enrolled in one of four cohorts: GCB-DLBCL EZH2 mutant cohort: Tumors must contain one, or more, of the following EZH2 activating mutations: Y641F; Y641N; Y641S; Y641H; Y641C; A677G; and/or A687V. GCB-DLBCL EZH2 wild type cohort: Tumors that do not contain one of the above mutations; Subjects with tumors harboring EZH2 mutations other than the seven outlined above will be enrolled in the EZH2 wild type cohort. tFL EZH2 mutant cohort: Tumors must contain one, or more, of the following EZH2 activating mutations: Y641F; Y641N; Y641S; Y641H; Y641C; A677G; and/or A687V. tFL EZH2 wild type cohort: Tumors that do not contain one of the above mutations; Subjects with tumors harboring EZH2 mutations other than the seven outlined above will be enrolled in the EZH2 wild type cohort
Patients who have benign or malignant soft tissue tumors of the extremities, flanks, pelvis, or shoulders that require surgical intervention
Index tumor involves the skull (treatment of other painful tumors in subjects with skull tumors is not excluded)
Patients who do not have pure uterine sarcomas (i.e., no mixed malignant Mullerian tumors).
Patients with advanced malignant solid tumors
Primary tumors of the sinuses, paranasal sinuses, or nasopharynx, or unknown primary tumors
Tumors that are invading a major vessel; NSCLC tumors abutting to a major vessel
Tumors of the lips, sinuses, salivary glands or nasopharynx.
Cavitary tumors or tumors invading or abutting large blood vessels
Has advanced gastrointestinal tumors refractory to at least 1 chemotherapy
Evidence of HER2 oncoprotein expression at the 2+ level by central laboratory. Patients whose tumors exhibit 2+ staining by IHC are eligible for the study.
Patients whose tumors score 1+ by conventional IHC, are non-amplified by FISH testing, and whose tumors score > or = 10.5 by HERmark® testing, are eligible for the study.
Patients with islet cell tumors or other non-epithelial cell malignancies of the pancreas.
Known advanced malignant hepatic tumors
Subjects with advanced or metastatic solid tumors for whom a chemotherapy regimen is considered appropriate
Histologically confirmed solid tumors, which may include but are not limited to rhabdomyosarcoma and other soft tissue sarcomas, Ewing sarcoma family of tumors, osteosarcoma, neuroblastoma, Wilms' tumor, hepatic tumors, germ cell tumors, primary brain tumors, NF-1 associated PF and LCH. In subjects with brain stem gliomas the requirement for histological confirmation can be waived if a biopsy was not performed. For plexiform neurofibromas, histologic confirmation of tumor is not necessary in the presence of consistent clinical and radiological findings, but should be considered if malignant degeneration of a PN is clinically suspected.
Phase 1: Subjects with advanced or metastatic solid tumors.
Measurable or evaluable disease according to RECIST for solid tumors or according to IWRC for NHL tumors
Patients who have mixed tumors with small-cell elements are ineligible
tumors must be measurable
Have any other functional tumors if they have familial Multiple Endocrine Neoplasia Syndrome 1 or 2 (MEN 1 or MEN 2).
Patients with central tumors within the proximal tree or touching the mediastinal pleura
Patients with infra-tentorial tumors are not eligible
Tumors that are Her2 positive are eligible
TanyN+M0 or T3-4N any M0 tumors
Tumors with significant involvement of the proximal stomach which, in the opinion of the treating thoracic surgeon, would require an esophagogastrectomy
For Part A, participants must have histologically confirmed solid tumors, CNS tumors, or lymphoma based upon biopsy or surgery at initial diagnosis and/or relapse/progression; the only exception to histologic confirmation is for pediatric tumors that are routinely diagnosed exclusively by standard clinical imaging criteria: diffuse intrinsic pontine glioma and optic pathway glioma
Metastatic solid tumors
Infratentorial tumors
Diagnostic categories\r\n* Sarcoma (soft tissue and bone)\r\n* Kidney tumors\r\n* Brain tumors\r\n* Other solid tumors (gonadal and germ cell tumors, retinoblastoma, neuroblastoma, and miscellaneous tumors)\r\n* Hodgkin lymphoma
Subjects must be at the recurrent/metastatic setting, with selected advanced solid tumors.
Benign tumors, neuroendocrine tumors, soft tissue tumors based on preoperative work-up or intraoperative findings
Tumors must be suitable for cryoablation
Index tumor involves the skull (treatment of other painful tumors in subjects with skull tumors is not excluded)
Patients with primary tumors located above the carina
Intracoelomic primary tumors or tumors expected to drain to an intracoelomic SLN
Patient with more than 3 tumors treated with any percutaneous ablation
Adults with intraocular tumors (melanoma, metastasis, retinal tumors) who are going to undergo enucleation diagnosed in the Emory Eye Center Ocular Oncology Service; patients will be assessed by a cardiologist or cardiology fellows
Patients in whom the tumor might not be accessible for peritumoral injection of indocyanine green, e.g. small, central tumors
Patients with known active advanced malignant solid tumors are excluded (except for basal or squamous skin cancers, or carcinomas in situ); patients with additional hematologic malignancies that require treatment are excluded
Tumors of or involving the midline, basal ganglia, or brain stem as assessed by MRI
Patients with T2b tumors or T3 tumors > 5 cm or patients with tumors involving the central chest/structures of the mediastinum
Prior craniotomy for resection of deep seated tumors in thalamus and brain stem
A known other currently active malignancy; (benign tumors and benign polyps, basal cell carcinomas of skin, superficial papillary bladder tumors, and pre-invasive carcinoma of the cervix are permitted)
Tumor tissue or blood collections from patients with benign tumors including but not limited to desmoid tumors, carcinoma in situ, or ongoing complete disease response (CR)
Germ cell tumors (GCTs).
Diffuse tumors or multiple malignant tumors in the breast.
synchronous tumors
Part 1: Subjects with advanced or metastatic solid tumors.
Part 1: Subjects with advanced or metastatic solid tumors
Tumors located in the central chest or other location where bleeding is associated with high morbidity
HER2 positive breast cancer or gastric cancer that is resistant to standard therapy or for which no standard therapy is available
PART I: participants must have histologically confirmed malignancy that is metastatic or unresectable and resistant to standard therapy or for which no standard therapy is available
Participants in combination therapy cohorts must have an advanced solid tumor where the use of nivolumab is standard therapy.
Pathologically-confirmed, locally advanced or metastatic solid tumors that have relapsed or are refractory to or are not considered medically suitable to receive standard of care treatment (Dose Escalation Phase)
Diagnosis of tumor type with the potential to have P-cadherin expression that is resistant to standard therapy or for which no standard therapy is available
Patients must have a histologically confirmed nonhematological, metastatic or locally advanced, incurable malignancy for which paclitaxel is clinically appropriate. Patients must have received and failed standard treatment for their malignancy; patients for whom no standard treatment is available will also be eligible.
Histologic evidence of advanced solid tumors (excluding central nervous system (CNS) primary tumors) non-resectable, refractory to standard therapies, or patient cannot receive or refuses standard therapy.
have tumors for which there is no standard therapy
Has a histologically or cytologically documented advanced solid tumor or lymphoma that has relapsed from or is refractory to standard treatment, or for which no standard treatment is available. Subjects with melanoma who are ineligible to receive or have declined ipilimumab treatment, or who are refractory or intolerant to ipilimumab may enroll.
Have a histologically confirmed diagnosis of an advanced solid tumor or lymphoma that has progressed in spite of at least one prior line of treatment, and for which additional effective standard therapy is not available. For this study, effective standard therapy is defined as treatment that has been shown to be curative and/or to prolong survival. In addition, subjects who are considered to not be candidates for standard therapy or who decline standard therapy are eligible for this study; in such cases, documentation of the reason for omitting or declining a standard therapy is required.
During Phase 1, subjects with locally advanced or metastatic solid tumors with disease progression on or after treatment with available therapies, or who are intolerant to treatment, or who refuse standard treatment.
Histologically or cytologically confirmed solid tumors of the types specified below, with incurable, locally advanced or metastatic disease that has failed standard therapy or for which no standard treatment option exists. For Ovarian Cancer
Progression after standard systemic therapy or a lack of available effective therapy, in the assessment of the Investigator.
Progression after standard systemic therapy or a lack of available effective therapy, in the assessment of the Investigator.
Histologically- or cytologically-documented, locally-advanced, or metastatic solid malignancy or lymphoma that is incurable and has failed prior standard therapy, or for which no standard therapy exists, or for which no standard therapy is considered appropriate
Standard treatment is not available
Malignancies for which there is no standard therapy, or previously treated locally advanced, refractory/relapsed or metastatic disease for which local curative surgery, curable radiotherapy, or satisfactory systemic anticancer therapy is no longer available
Phase 1a: histological or cytological confirmation of a solid, malignant tumor, excluding CNS tumors, that is refractory to standard therapies or for which no standard therapies exist.
(Part 1 only) Have a histologically or cytologically confirmed diagnosis of advanced solid tumor that has relapsed or is refractory to standard curative or palliative therapy or has a contraindication to standard therapy.
Patients must have histologically confirmed solid tumors for which all standard therapy known to prolong survival have failed or for which standard therapies do not exist
For the cohort 1, eligible patients must have a histologically, cytologically or radiographically proven metastatic or locally advanced solid tumor of any type, for which there is no curative standard therapy or standard therapy has failed
Patients must have a diagnosis of a solid tumor malignancy and is refractory to standard therapies who have relapsed after standard therapy, or whose cancers have no standard therapy.
For the dose escalation phase: Patients with histologically or cytologically confirmed locally advanced or metastatic solid tumor and have failed available standard of care (SoC) therapy and for whom no curative therapy is available or who are not eligible, intolerant to or refuse standard therapy.
Has relapsed from or is refractory to standard treatment or for which no standard treatment is available
Patient must have recurrent or advanced cancer (i.e., solid tumors) for whom standard therapy offers no curative potential.
All patients must be refractory to approved standard systemic therapy
Patients with advanced cancer that is refractory to standard therapy, or that has either relapsed after standard therapy or has no standard therapy that increases survival by at least three months
Patients with histologically confirmed inoperable, recurrent or metastatic malignant solid tumors, deemed incurable, and who have either:\r\n* Failed to respond to standard therapy or\r\n* For whom no standard therapy is available or\r\n* Refuse to receive standard therapies
Patients with advanced solid tumors that are refractory to approved therapy and have had at least one line of systemic treatment with chemotherapy, immunotherapy, hormonal therapy, or other standard treatments for metastatic disease
Patients must have a diagnosis of advanced or metastatic malignancy that is refractory to standard therapies, who have relapsed after standard therapy, or whose cancers have no standard therapy that induces a complete response (CR) rate of at least 10% or improves survival by at least three months
Patients with advanced or metastatic cancer that is refractory to standard therapy or that has relapsed after standard therapy or has no standard therapy that increases survival by at least three months
PHASE I: Patients must have advanced solid tumor that is resistant or refractory to standard therapy
Dose Escalation Cohort: Patients must have a diagnosis of a histologically confirmed solid tumor that is incurable and refractory to standard therapy or for which no standard therapy exists
Subjects with solid tumor types other than TNBC may also be enrolled after discussion with the sponsor; these subjects must have a diagnosis of a histologically confirmed solid tumor that is incurable and refractory to standard therapy or for which no standard therapy exists
Histologically or cytologically confirmed advanced or metastatic solid tumor or l lymphoma, that is refractory to standard therapy, relapsed after standard therapy, or for which no standard therapy available that is expected to improve survival by at least three months
Patients for whom there is no further standard therapy available at the time of enrollment (Part A)
PHASE I STUDY ELIGIBILITY CRITERIA:\r\nPatients must have histologically or cytologically confirmed advanced solid tumor that is refractory to standard treatment or for which no standard treatment exists
ELIGIBILITY CRITERIA- LYMPHODEPLETION/INFUSION OF tvs-CTL: Recurrent, refractory or relapsed advanced stage melanoma defined as progression of disease through standard therapy or patient choice to not receive standard therapy; for those that received standard systemic therapy, treatment agents may have included (but are not limited to) ipilimumab or vemurafenib (for those patients that are BRAF v600e positive)
Patients with an advanced solid tumor that is refractory to standard treatment, or for which no standard therapy is available, or the subject refuses standard therapy
Patients must have pathologically-confirmed solid tumors, refractory after standard therapy for the disease or for which conventional systemic chemotherapy is not reliably effective or no effective therapy is available.
Patients with advanced or metastatic cancer that is refractory to standard therapy, relapsed after standard therapy, or who have no standard therapy available that improves survival by at least three months
Patients with advanced or metastatic cancer that is refractory to standard therapy, relapsed after standard therapy, or have no standard therapy that induces a complete response of at least 10% or improves survival by at least three months; in addition, patients with disease that are “benign” by pathology, but relentlessly progressive, leading to disability, pain, and premature death in the majority of cases (including, but not limited to lymphangioleiomyomatosis [LAM], type 2 neurofibromatosis [NF], Erdheim Chester disease, and Castleman’s disease) may also be considered for enrollment
Patients with advanced or metastatic cancers and BRAF mutations that are refractory to standard therapy, relapsed after standard therapy, or who have no standard therapy available that improves survival by at least three months; patients with BRAF mutation in cell free deoxyribonucleic acid (DNA) (tested in Clinical Laboratory Improvement Amendments [CLIA] lab) are also eligible
Patients with advanced or metastatic cancer that is refractory to standard therapies, who have relapsed after standard therapy, or whose cancers have no standard therapy that induces a complete response (CR) rate of at least 10% or improves survival by at least three months
Histologically and/or cytologically confirmed malignant solid tumor that is refractory to standard therapies, or for which no standard therapies exist; disease must be measurable by Response Evaluation Criteria in Solid Tumors (RECIST) criteria\r\n* For the non-small cell lung cancer (NSCLC) expanded cohort only: only histologically proven adenocarcinoma that is refractory to standard therapies
Unresectable, locally advanced or metastatic solid tumor for which no standard therapy is recognized or for which standard therapy has failed
Has disease that is refractory to or intolerable with standard treatment, or for which no standard treatment is available
Patient with documented pathological evidence of a cancer from which has developed advanced unresectable solid tumors that are, in the opinion of their treating physician, refractory to standard therapy or for which no standard therapy is available
Subjects must have a pathologically documented, definitively diagnosed, advanced solid tumor that is refractory to standard treatment, for which no standard therapy is available, or the subject refuses standard therapy
For the dose escalation part: Patients with histologically confirmed, locally advanced or metastatic solid tumors who are not candidates for or refuse standard therapy or whose disease progressed and for which standard anti-cancer treatment is no longer effective, excluding primary brain or spinal tumors.
Patient has advanced or metastatic breast cancer that is refractory to at least one standard therapy or that has relapsed after standard therapy or that has no standard systemic therapy that increases survival by at least 3 months.
For the dose escalation part: Patients with selected, relapsed solid tumors who have failed available standard therapy or who are not candidates for standard therapy.
For the expansion part: Patients with relapsed, advanced and/or metastatic solid tumors who are not candidates for standard therapy
Patients must have relapsed after or be refractory to effective standard therapies; for NF1 PN there is no standard medical therapy, and therefore no requirement for prior therapy; there are no limits on number of prior therapeutic regimens
COHORT I (DOSE ESCALATION): histologic proof of cancer that is now unresectable, not amenable to any other standard therapies, or patient refuses standard therapy
STANDARD RISK PATIENTS:
Advanced (unresectable) solid tumors: patients must have failed or been intolerant to at least one line of standard therapy or refuse standard treatment
Patients with histologically confirmed inoperable, recurrent or metastatic malignant solid tumors, deemed incurable, and who have either:\r\n* Failed to respond to standard therapy or\r\n* For whom no standard therapy is available or\r\n* Refuse to receive standard therapies\r\n** The study is intended to enroll patients with melanoma, renal cell, and pancreatic cancer; patients with other types of solid tumors will require approval by the principal investigator
Patients must have histologically proven solid tumors (Phase I) with biopsiable tumor (expansion cohort) refractory to standard therapy or for whom no standard therapy exists or who decline standard therapy
Histologically or cytologically confirmed diagnosis of advanced solid tumors that have relapsed from or are refractory to standard treatment or for which no standard treatment is available
Diagnosis - Dose Escalation Phase: Histologically or cytologically confirmed diagnosis of advanced solid tumor that is resistant to standard therapy or for which no standard therapy is available.
Pathologically documented, advanced colorectal, pancreatic or non-small cell lung cancer that is refractory to standard treatment, or the subjects have been intolerant to or refuse standard treatment.
Part A: histologically or cytologically confirmed advanced malignant solid tumor that is refractory to or intolerant of standard therapy or for which no standard therapy is available
Patients must have a histologically confirmed non-hematological malignancy established by biopsy or resection; patients must have received and failed standard treatment for their malignancy; patients for whom no standard treatment is available will also be eligible
Subjects must have no standard therapy available, or have actively refused standard therapy
Histologically or cytologically confirmed metastatic breast cancer relapsed or refractory to approved standard available treatment
Patients must have a diagnosis with solid tumors and lymphomas, either refractory to standard therapy or for which no effective standard therapy that conveys clinical benefit
Patients with relapsed, advanced and/or metastatic cancer who have failed available standard treatments or who are not candidates for standard therapy. Patients must have measurable disease
Patients with advanced or metastatic cancers that are refractory to standard therapy, relapsed after standard therapy, or who have no standard therapy available that improves survival by at least three months.
Subject has histologic or cytologic confirmation of advanced solid tumors that is refractory to standard therapy or for which no standard therapy is available
Patients must have histologically confirmed solid tumor malignancy (excluding primary brain tumor) that is metastatic or unresectable and have failed standard therapies; patients are also eligible patients declined (or if their physicians determined them unsuitable for) standard therapy options.
For the dose-escalation cohorts: Subjects with histologically or cytologically confirmed advanced malignancies (solid tumors), refractory to any standard therapy, have no standard therapy available
For the expansion cohort: Subjects with advanced, histologically or cytologically confirmed triple-negative breast cancer (TNBC), refractory to any standard therapy, have no standard therapy available, or subjects actively refused any standard treatment and / or if, in the judgment of the investigator, experimental treatment is clinically acceptable.
Dose Escalation Cohort only: Confirmed advanced solid tumor or lymphoma for which standard curative or palliative measures do not exist or are no longer effective; subjects with progressive brain metastases are also eligible. OR Confirmed Histological/cytological hematological malignancy that is refractory to/relapsed after and/or intolerant of standard therapies or for which no standard therapy exists. OR Confirmed high grade glioma (grade 3and4) that is relapsed/refractory to standard therapies and who have progressive disease following radiation therapy. Patients with any number of prior treatments are allowed.
Had received standard treatment (no limitations for prior therapies), and in treating physician’s opinion, no suitable standard treatment is available, or for those subjects who decline chemotherapy
Patients with advanced or metastatic cancer that is refractory to standard therapy or has relapsed after standard therapy
Patients with advanced or metastatic cancer that is refractory to standard therapy, relapsed after standard therapy, or have no standard therapy that induces a complete response (CR) rate of at least 10% or improves survival by at least three months
Histologically or cytologically documented locally-advanced and/or metastatic solid malignancy that is incurable, and has failed prior standard therapy or for which standard therapy is not appropriate
Histologically or cytologically documented, unresectable, locally advanced or metastatic solid tumor for which no standard therapy is recognized or for which standard therapy has failed
Refractory to standard therapy, relapsed after standard therapy, or have no standard therapy that increases survival at least 3 months
Failed to respond to or relapsed following standard treatment, or declined or was not eligible for standard treatment.
For dose escalation part: Histologically or cytologically proven metastatic or locally advanced solid tumors, for which no standard therapy exists or standard therapy has failed
Patients with advanced or metastatic cancers with no available standard therapy are eligible to enter the phase 1 portion of this study
Patients must have pathologically-confirmed acute leukemia, refractory or relapsed after standard therapy for the disease or for which conventional systemic chemotherapy is not reliably effective or no effective therapy is available Phase II Only: Patient must have histologically or pathologically confirmed diagnosis of AML based on WHO classification that is refractory after standard therapy, or for which conventional systemic chemotherapy is not reliably effective, or no effective therapy is available. Patients aged 60 years or older with newly diagnosed AML who are not eligible for, or who refuse, standard care are also eligible.
In the dose-escalation phase: histologically- or cytologically- confirmed advanced solid tumor that is refractory to standard therapy and for which no standard therapy exists.
Patient must have histologically or cytologically confirmed diagnosis of advanced solid tumor or lymphoma harboring a B-Raf proto-oncogene, serine/threonine kinase (BRAF) mutation, for which no standard therapy is available, is resistant/refractory to standard therapy, has relapsed after standard therapy, or has no standard therapy that improves survival by at least three months
Patients with advanced solid tumor that is refractory to standard treatment, for which no standard treatment is available, or the patient refuses standard therapy.
Patients with advanced cancer should be refractory to standard therapy, relapsed after standard therapy, or have no standard therapy available that improves survival by at least three months
Patients with advanced cancer, either refractory to standard therapy or for which no effective standard therapy that increases survival for at least 3 months is available
Dose Escalation phase: Patients with solid tumors (including melanoma) who have failed or are not candidates for standard therapies of for whom no approved therapy is available
Histologically or cytologically confirmed diagnosis of a solid malignancy with advanced disease that has relapsed, that is refractory to standard therapies, or for which there is not standard therapy, or for which the patient opts not to receive standard therapy; patients with tumor types in which carboplatin and paclitaxel is appropriate as a first-line regimen for advanced disease are eligible
Patients with advanced or metastatic cancers that are refractory to standard therapy, relapsed after standard therapy, or who have no standard therapy available that improves survival by at least three months
Patients with pathologically confirmed advanced or metastatic cancer that is refractory to standard therapy, relapsed after standard therapy, or who have had no standard therapy that induces a complete response (CR) rate of at least 10% or improves survival by at least three months
Patients with advanced or metastatic cancer that is refractory to standard therapy, relapsed after standard therapy, or have no standard therapy that induces a complete response (CR) rate of at least 10% or improves survival by at least three months
Histologically or cytologically proven metastatic or locally advanced solid tumors for which no standard therapy exists or standard therapy has failed. Availability of tumor archival material or fresh biopsies is optional for subjects in dose escalation.
Patients with advanced or metastatic cancer that is refractory to standard therapy, relapsed after standard therapy, or have no standard therapy that induces a complete response (CR) rate of at least 10% or improves survival by at least three months
Locally advanced or metastatic solid tumors with the exception of primary brain tumor, and have failed standard of care therapy
Solid tumors refractory to standard therapy
Patients with histologically confirmed solid tumors who: o Part 1: have tumor progression following standard therapy, have treatment-refractory disease, or for whom there is no effective standard of therapy
Patients must have histologically or cytologically confirmed AML, other than acute promyelocytic leukemia, as defined by the 2008 World Health Organization (WHO) criteria that have relapsed or refractory to standard chemotherapy; unsuitable for standard chemotherapy or unwilling to undergo standard chemotherapy; subjects >= 60 years of age with newly diagnosed AML who are not candidates for or have refused standard chemotherapy are eligible
Confirmed relapsed or refractory locally advanced or metastatic solid cancer for whom no standard therapy is considered appropriate, or for whom standard therapy is considered intolerable.
Subjects must have histologically or cytologically confirmed locally advanced or metastatic solid tumors and must be refractory to any standard therapy, or have no standard therapy available, or have actively refused any standard therapy or, in the investigator's opinion, experimental treatment in this study is clinically and ethically acceptable for the subject.
Subjects with advanced, histologically or cytologically confirmed tumor, refractory to any standard treatment, with no standard therapy available, in whom standard therapy is not a therapeutic option or the subject actively refuses use of chemotherapy which would be regarded standard and/or if in the judgment of the investigator, experimental treatment is clinically and ethically acceptable.
Histologically or cytologically confirmed advanced solid tumors that are refractory to standard therapy or for which no standard therapy exists (Monotherapy and in Cohorts A and B)
Diagnosis of solid tumor that is advanced/metastatic and resistant to standard therapy or for whom no standard therapy is available
Diagnosis of solid tumor that is advanced/metastatic and resistant to standard therapy or for which no standard therapy is available.
Male or female patient with Glypican 3 positive advanced solid tumor not amenable to standard therapy or for which standard therapy is not available or not indicated
Advanced breast cancer with HER2 overexpression that is refractory to or intolerable with standard treatment, or for which no standard treatment is available.
Advanced breast cancer with HER2 low expression that is refractory to or intolerable with standard treatment, or for which no standard treatment is available. Part 2d:
Advanced/unresectable or metastatic tumor with HER2 mutation that is refractory to or intolerable with standard treatment, or for which no standard treatment is available. Part 2e:
Advanced breast cancer with HER2 overexpression that is refractory to or intolerable with standard treatment, or for which no standard treatment is available.
Part 1, Part 2b, Part 2d, and Part 2e: Patients with advanced solid tumors who have tumor progression following standard therapy, have treatment-refractory disease, or for whom there is no effective standard of therapy.
Subjects with advanced, histologically or cytologically confirmed advanced malignancies (solid tumors), refractory to any standard therapy, have no standard therapy available, or subjects actively refused any standard treatment and / or if, in the judgment of the investigator, experimental treatment is clinically and ethically acceptable.
Patients with recurrent metastatic or locally advanced disease considered refractory or intolerant to all standard treatment available for their tumor, or those tumors for which no standard treatment is available
Advanced/metastatic solid tumor refractory to standard therapy
Pathologically-documented, definitively-diagnosed AML that is relapsed or refractory to standard treatment, for which no standard therapy is available or the subject refuses standard therapy
Histologically confirmed cancers (excluding melanoma and papillary thyroid cancer) with a BRAF V600 mutation and that are resistant to standard therapy or for which standard or curative therapy does not exist
Patients with relapsed, advanced and/or metastatic cancer who have failed available standard treatments or who are not candidates for standard therapy. Patients must have measurable disease
Group 1: Histologically or cytologically confirmed advanced malignant solid tumor or lymphoma (any subtype) that is refractory to or intolerant of standard therapy or for which no standard therapy is available
Progression on standard therapies or withdrawn from standard treatment due to unacceptable toxicity. Previous standard treatment must include all of the following:
Diagnosis of advanced/metastatic solid tumor that is resistant to standard therapy or for which no standard therapy is available
Diagnosis of solid tumor that is advanced/metastatic and resistant to standard therapy or for whom no standard therapy is available
Has a histologically or cytologically documented advanced solid tumor or lymphoma that has relapsed from or is refractory to standard treatment, and for whom no standard treatment is available.
Have advanced or metastatic disease refractory to standard curative or palliative therapy or contraindication to standard therapy
Advanced or metastatic solid tumor refractory to standard therapy
Patients with histologically or cytologically confirmed, locally advanced or metastatic solid tumors who are not candidates for standard therapy or in whom regorafenib or cetuximab is considered a standard treatment. Patients with metastatic colorectal cancer (mCRC) must have a record of K-ras gene mutational analysis available and no K-ras mutation is present.
Histologically/cytologically confirmed advanced or metastatic solid tumors who have failed standard therapy or for whom no effective standard anti-cancer therapy exists
For dose escalation cohorts: Subjects with advanced, histologically or cytologically confirmed solid tumors are eligible. Subjects' tumors (all comers) must be refractory to standard treatment with no standard therapy available, or subjects actively refuse any treatment, which would be regarded standard. In addition, the investigator must judge the experimental treatment as clinically and ethically acceptable
Patients with a malignancy that is either refractory to standard therapy or for which no standard therapy is available.
Part 1 only: Patients with histologically or cytologically proven progressive or metastatic solid tumors who have failed standard treatment and have no other effective treatment available. Part 2 only: Patients with histologically or cytologically proven progressive or metastatic solid tumors who have failed standard treatment and have no other effective treatment available, or docetaxel-naive patients who have failed standard treatment and have tumors for which a docetaxel-based regimen would be appropriate.
Arm 1 only: Histologically confirmed malignant solid tumor which is refractory to or has failed standard treatments, or participant is not considered medically suitable to receive standard of care treatment or refuses standard of care treatment
Pathologically documented, definitively diagnosed, advanced solid tumor that is refractory to standard treatment, or which no standard therapy is available, or the subject refuses standard therapy or multiple myeloma
Pathologically confirmed solid tumor, locally advanced / metastatic, refractory after standard therapy, or for which no effective curative or surgical treatment options are available
Histologically or cytologically confirmed solid tumors known to express C4.4a (eg, carcinomas of the lung, head & neck SCC, esophagus SCC (squamous cell carcinoma),colon, ovary, prostate, and breast) that are refractory to any standard therapy, or have no standard therapy available, or for which subjects actively refuse any treatment that would be regarded as standard and in whom, in the opinion of the investigator, experimental therapy with BAY1129980 may be beneficial.
Histologically- or cytologically-confirmed advanced/metastatic solid tumor or lymphoma that is refractory to standard therapies, or the patient refuses standard therapy
Histologically or cytologically confirmed solid tumors that are refractory to standard therapy or for which no standard therapy exist
Patients with advanced cancer should be refractory to standard therapy, relapsed after standard therapy, or have no standard therapy that improves survival by at least three months
Histologically or cytologically documented, incurable, locally advanced or metastatic solid tumors or recurrent malignant lymphoma in subjects who failed standard therapy or for whom standard or curative therapy does not exist or is not tolerable.
locally advanced or metastatic solid tumors with the exception of primary brain tumor, and have failed or are not eligible for standard of care therapy.
Patients with advanced cancer, either refractory to standard therapy or for which no effective standard therapy that increases survival for at least 3 months if available
Subjects with advanced or metastatic solid tumors (non-hematologic refractory to or relapsed from standard therapies or for which there is no known effective treatment during dose escalation
Patients with confirmed diagnosis of advanced solid tumors (dose-escalation phase) or another solid tumor type based on antitumoral activity (dose-expansion phase) that are not responsive to standard therapy or for which no standard therapy exists
Patients with advanced or metastatic cancer that is refractory to standard therapy, relapsed after standard therapy, or has no standard therapy that improves survival by at least three months
Histologically or cytologically confirmed solid tumor that has recurred after standard therapy, or for which there is no standard therapy. Subjects with brainstem glioma DO NOT need histologic proof of the diagnosis.
(Part A only) Histologically or cytologically confirmed metastatic and/or advanced solid tumors or lymphomas for which no standard therapy exists, or who are not eligible for standard treatment. Subjects must have received at least one prior therapy for their malignancy;
Participant in the dose escalation cohorts must have histological confirmation of locally advanced or metastatic solid tumor that is either refractory after standard of care therapy for the disease or for which standard of care therapy or does not exist.
For the dose escalation cohorts, histologically-proven metastatic colorectal adenocarcinoma that is refractory to 2 prior standard treatment regimens or standard treatment was declined.
For the dose expansion cohorts, histologically-proven metastatic colorectal adenocarcinoma that is refractory to 1 prior standard treatment regimen or standard therapy was declined.
Relapsed or refractory malignant solid tumors of any histology for which no standard curative therapy is available (escalation phase).
Has failed standard treatment
The participant has histologically or cytologically advanced solid tumor that is resistant to standard therapy or for which there is no standard therapy.
The participant has histologically or cytologically confirmed advanced solid tumor that is resistant to standard therapy or for which there is no standard therapy.
Histologically or cytologically confirmed non-CNS solid tumor that recurred after standard/frontline therapy, or for which there is no standard/frontline therapy available.
Patients with advanced cancer who are refractory to, have demonstrated intolerance to, or have refused access to, available standard therapies
Patients must have histologically confirmed solid tumors for which standard therapy known to prolong survival has failed in the metastatic setting or for which standard therapies do not exist