NCT02587962

Dose-escalation Study of Birinapant and Pembrolizumab in Solid Tumors

A Phase 1/2 Multicenter, Single-Arm, Open-Label, Dose-Escalation Study of Birinapant in Combination With Pembrolizumab (KEYTRUDA®) in Patients With Relapsed or Refractory Solid Tumors

• Status: Terminated
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 34 (actual)
• Sponsor: Medivir · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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.

Conditions

• Solid Tumors

Interventions

Type	Name	Description
DRUG	Birinapant	Birinapant intravenous (IV) on Days 1 and 8 of each 21-Day Cycle. The following escalating doses of birinapant to be studied: 5.6, 11, 17, and 22 mg/m2. In the expansion phase the assigned recommended phase two dose will be administered in all cohorts
DRUG	Pembrolizumab	200 mg pembrolizumab IV on Day 1 of each 21-Day Cycle

Timeline

• Start date: 2017-08-04
• Primary completion: 2020-02-17
• Completion: 2020-02-17
• First posted: 2015-10-27
• Last updated: 2021-01-14
• Results posted: 2021-01-14

Locations

9 sites across 1 country: United States

Regulatory

• FDA-regulated drug study