NCT02259114

A Dose-Finding Study of Birabresib (MK-8628), a Small Molecule Inhibitor of the Bromodomain and Extra-Terminal (BET) Proteins, in Adults With Selected Advanced Solid Tumors (MK-8628-003)

A Phase IB Trial With OTX015/MK-8628, a Small Molecule Inhibitor of the Bromodomain and Extra-Terminal (BET) Proteins, in Patients With Selected Advanced Solid Tumors

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 47 (actual)
• Sponsor: Oncoethix GmbH, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA) · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Open-label, phase I, non-randomized, multicentric study of single-agent birabresib (MK-8628) (formerly known as OTX015) administered according to two distinct regimens to participants with selected advanced tumors. The study will be performed in two parts. Dose Escalation Part: This step is designed to determine the maximum tolerated dose (MTD) in each of the two regimens, which will be evaluated in parallel. Participants will receive oral birabresib according to: Continuous Dosing Regimen: continuous, once daily for 21 consecutive days (21-day cycles). OR Days 1-7 Dosing Regimen: once daily on Days 1 to 7, repeated every 3 weeks (21-day cycles; 1 week ON/2 weeks OFF). Participants will be sequentially assigned to Continuous Dosing Regimen or Days 1-7 Dosing Regimen according to the next available place and receive birabresib at escalating doses levels (DL). Cohorts of 3 participants will be treated, and an additional 3 participants will be treated at the first indication of dose-limiting toxicity (DLT). MTD assessment will be based on the tolerability observed during the first 21 days of treatment. Expansion Part: The efficacy of birabresib in each of the five indications (i.e., Bromodomain-Nuclear Protein in Testis \[BRD-NUT\] midline carcinoma, triple negative breast cancer \[TNBC\], non-small cell lung cancer \[NSCLC\] harboring a rearrangement Anaplastic Lymphoma Kinase \[ALK\] gene/fusion protein or Kirsten Ras \[KRAS\] mutation, castrate-resistant prostate cancer, and pancreatic ductal carcinoma) will be assessed in terms of response (Response Evaluation Criteria in Solid Tumors v1.1 \[RECIST v1.1\] or Prostate Cancer Clinical Trials Working Group 2 \[PCWG2\]) using a selected regimen.

Conditions

• NUT Midline Carcinoma
• Triple Negative Breast Cancer
• Non-small Cell Lung Cancer With Rearranged ALK Gene/Fusion Protein or KRAS Mutation
• Castrate-resistant Prostate Cancer
• CRPC
• Pancreatic Ductal Adenocarcinoma

Interventions

Type	Name	Description
DRUG	Birabresib	Birabresib 10, 20 and/or 40 mg oral capsules

Timeline

• Start date: 2014-10-23
• Primary completion: 2017-03-03
• Completion: 2017-03-03
• First posted: 2014-10-08
• Last updated: 2021-01-26
• Results posted: 2018-10-01

Regulatory

• FDA-regulated drug study