Dose-escalation Study of Birinapant and Pembrolizumab in Solid Tumors

Status: Active

Description

An ascending dose study in patients with solid tumors to evaluate the safety, tolerability, pharmacodynamics and efficacy of birinapant when given in combination with pembrolizumab. A dose expansion phase of 4 cohorts will also be included.

Eligibility Criteria

Inclusion Criteria

  • Inclusion Criteria: - Histologically confirmed solid malignancy that is metastatic or unresectable for which standard curative or palliative measures do not exist or are no longer effective (Dose Escalation phase only) - Measurable disease according to RECIST v 1.1 - Eastern Cooperative Oncology Group (ECOG) score of 0 or 1 - Normal organ and marrow function Dose Expansion phase specific additional inclusion criteria: - Patients with metastatic colorectal cancer with no available therapy options that are known to provide clinical benefit per institutional standard of care. (colorectal cancer cohort only) - Patients must have a histologically confirmed epithelial ovarian cancer, primary peritoneal cancer or fallopian tube solid tumor cancer that is locally advanced or metastatic with no available therapy options that are known to provide clinical benefit per institutional standard of care. (ovarian cancer cohort only) - Patients must have histologically or cytologically confirmed cervical squamous cell carcinoma that is locally advanced or metastatic with no available therapy options that are known to provide clinical benefit per institutional standard of care. (cervical cancer cohort only) - Patients must have histologically or cytologically confirmed head and neck squamous cell carcinoma that is locally advanced or metastatic with no available therapy options that are known to provide clinical benefit per institutional standard of care. (various solid tumors cohort: head and neck squamous cell carcinoma groups only). - Patients must have received prior therapy with an anti-PD-1 or anti-PD-L1 antibody, or previously participated in Merck MK 3475 clinical trials. Patients must have experienced documented, confirmed radiographic progression of disease by iRECIST, or by RECIST v1.1 (various solid tumors cohort head and neck squamous cell carcinoma, Check point inhibitor experienced group only). - Patients must have histologically or cytologically confirmed small cell lung carcinoma that is locally advanced or metastatic with no available therapy options that are known to provide clinical benefit per institutional standard of care. (various solid tumors cohort, SCLC group only) - Patients must have histologically or cytologically confirmed cholangiocarcinoma that is locally advanced or metastatic with no available therapy options that are known to provide clinical benefit per institutional standard of care. (various solid tumors cohort, cholangiocarcinoma group only) - Patients must have histologically or cytologically confirmed mesothelioma that is locally advanced or metastatic with no available therapy options that are known to provide clinical benefit per institutional standard of care. (various solid tumors cohort, mesothelioma group only) - Patients must have histologically or cytologically confirmed carcinoma of the esophagus including the gastroesophageal junction that is locally advanced or metastatic with no available therapy options that are known to provide clinical benefit per institutional standard of care. (various solid tumors cohort, gastroesophageal carcinoma group only) Exclusion Criteria: Exclusion criteria apply to all phases and cohorts in the study unless otherwise stated - Prior monoclonal antibody, within 4 weeks prior to first dose of study drug. - Prior chemotherapy, targeted small molecule therapy or radiotherapy within 2 weeks prior to first dose of study drug. - Patients who have received any other investigational agents within 4 weeks of first dose of study drug. - Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody. (Not applicable for various solid tumors cohort, head and neck squamous cell carcinoma check-point inhibitor experienced group) - History of allergic reactions attributed to compounds of similar chemical or biologic composition to birinapant or pembrolizumab or their constituents. - Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, hypertension, unstable angina pectoris, cardiac arrhythmia, autoimmune disease or inflammatory diseases, or psychiatric illness/social situations that would limit compliance with study requirements. - Evidence of active, non-infectious pneumonitis or a history of interstitial lung disease. - Known history of Human Immunodeficiency Virus (HIV (HIV1/2 antibodies), or Active Hepatitis B (HBsAg reactive. Active Hepatitis C (HCV-RNA qualitative). - Currently breast feeding, pregnant or planning to conceive or father Children from screening through 120 Days after last dose of study drug. - Patients who have received anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways) (Various solid tumor cohort, head and neck squamous cell carcinoma check point inhibitor experienced group only)

Locations & Contacts

Maryland

Baltimore
Johns Hopkins University / Sidney Kimmel Cancer Center
Status: Active
Name Not Available

Pennsylvania

Philadelphia
Thomas Jefferson University Hospital
Status: Temporarily closed to accrual
Name Not Available

Texas

Houston
M D Anderson Cancer Center
Status: Active
Name Not Available

Trial Objectives and Outline

This study will be conducted in two phases. The Phase 1 portion of the study will employ a sequential group dose-escalation design to determine the dose-limiting toxicity (DLT) and recommended Phase 2 dose (RP2D) of birinapant administered in combination with 200 mg pembrolizumab, both administered as a 30-minute intravenous (IV) infusion. The following proposed doses of birinapant are to be evaluated: 5.6, 11, 17, and 22 mg/m2. The Phase 2 portion, the dose expansion phase, will compromise 4 cohorts of 26-30 patients. The 4 cohorts will include the following: - Colorectal cancer - Ovarian Cancer - Cervical cancer - Various solid tumors (30 patients, including 5 patients with each of the following 6 tumor types: Head and Neck Squamous Cell Carcinoma (HNSCC)-checkpoint-inhibitor naïve; and HNSCC checkpoint-inhibitor experienced; Gastroesophageal carcinoma; Mesothelioma; Small cell lung cancer (SCLC); Cholangiocarcinoma A Simon's 2-stage design will be used for each of the cohorts in colorectal cancer, ovarian cancer and cervical cancer. A predefined interim analysis allowing stopping each of these cohorts for futility and safety will be conducted in the first stage to limit undue exposure before further inclusion into a given cohort. The design of the various solid tumors cohort will limit undue exposure in any of the selected tumor types by limiting the number of enrolled patient to five in each tumor type.

Trial Phase & Type

Trial Phase

Phase I/II

Trial Type

Treatment

Lead Organization

Lead Organization
Medivir

Trial IDs

Primary ID BPT-201
Secondary IDs NCI-2015-01955, MK3475 KEYNOTE KN163, TL32711-POC-0103-PTL
Clinicaltrials.gov ID NCT02587962