Participant has histological confirmation of a locally advanced or metastatic solid tumor of a type associated with Prolactin Receptor (PRLR) expression that has progressed on prior treatment, is not amenable to treatment with curative intent, and has no other therapy options known to provide clinical benefit or the subject is ineligible for such therapies.
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;
Histologically confirmed advanced solid tumors with no clear curative treatment options available after at least prior systemic anticancer therapy.
Patient with advanced or metastatic solid tumor and has disease progression or treatment intolerance after treatment with available therapies
Previously treated for advanced cancer with no additional therapy options available known to prolong survival.
Dose escalation:\r\n* Any locally advanced or metastatic solid tumor malignancy with no curative treatment options available
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 .\n\n - Eastern Cooperative Oncology Group (ECOG) score of or \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- or anti-PD-L antibody, or\n previously participated in Merck MK clinical trials. Patients must have\n experienced documented, confirmed radiographic progression of disease by iRECIST, or\n by RECIST v. (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 weeks prior to first dose of study drug.\n\n - Prior chemotherapy, targeted small molecule therapy or radiotherapy within weeks\n prior to first dose of study drug.\n\n - Patients who have received any other investigational agents within weeks of first\n dose of study drug.\n\n - Prior therapy with an anti-PD-, anti-PD-L, anti-PD-L, anti-CD, or anti-Cytotoxic\n T-lymphocyte-associated antigen- (CTLA-) 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 (HIV/ 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 Days after last dose of study drug.\n\n - Patients who have received anti-PD-L, anti-CD, or anti-Cytotoxic\n T-lymphocyte-associated antigen- (CTLA-) 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)
Must have failed or be unable to tolerate or refused other available Food and Drug Administration (FDA) approved effective therapies; NOTE: patients should not have other treatment options considered curative
Have a histologically confirmed advanced solid tumor for which curative treatment is not available
Advanced solid tumor malignancy without curative options
No available curative treatment options, a limited prognosis of several months to < years anticipated survival with currently available therapies, and progressive or relapsed disease
Male or female subjects with AML with no available curative treatment options using currently available therapies
Have a histologically confirmed advanced solid tumor for which curative treatment is not available
Subject must have advanced solid tumor that is not amenable to surgical resection or other approved therapeutic options that have demonstrated clinical benefit but based on evidence gathered in this study or from external sources, the Sponsor in consultation with the Investigators, may decide to limit to specific tumor types.
Relapsed or refractory solid tumor malignancy that has progressed on standard anticancer therapy with no available curative options. (Note: Osteosarcoma participants must be in first or subsequent relapse [greater than or equal to first relapse]). Only the osteosarcoma participants enrolled to Cohorts A and B must be deemed candidates for ifosfamide and etoposide chemotherapy).
Previously treated for advanced cancer and there are no curative therapy options available
Previously treated for advanced cancer with no additional therapy options available known to prolong survival
Subjects with CD+ B cell lymphomas with no available curative treatment options (such as autologous or allogeneic stem cell transplant [SCT]) who have a limited prognosis (several months to < year survival) with currently available therapies
Has relapsed or refractory disease and no standard treatment options as determined by locally or regionally available standards of care and treating physician's discretion
Subject must have advanced solid tumor that is not amenable to surgical resection or other approved therapeutic options that have demonstrated clinical benefit.
Advanced or metastatic colorectal cancer with no curative options available and progression on previous standard therapy, including an EGFR inhibitor if KRAS wild-type
Advanced solid tumor for which no other higher priority therapies are available
Must have advanced disease and no standard treatment options as determined by locally/regionally available standards of care and treating physician's discretion
Subject has no available or declines curative treatment options such as allogeneic stem cell transplant (SCT) and has limited prognosis (< years survival) with currently available therapies
Phase Ia: Patients may have de novo metastatic disease, or documented progression despite any number of prior therapies; patients must have no curative or other effective therapeutic options available
Patient must not have curative options available (e.g. a single metastatic focus in the liver in a patient with MCRC eligible for metastasectomy).
Histologically or cytologically confirmed advanced solid tumor with no available standard treatment options in the opinion of the investigator.
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 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
Participants with advanced solid tumor that is not amenable to surgical resection or other approved therapeutic options.
