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