NCT05372640

Testing the Safety and Efficacy of the Combination of Two Anti-cancer Drugs, ZEN003694 and Abemaciclib, for Adult and Pediatric Patients (12-17 Years) With Metastatic or Unresectable NUT Carcinoma, Breast Cancer and Other Solid Tumors

A Phase 1 Study of BET Bromodomain Inhibitor ZEN003694 in Combination With the CDK4/6 Inhibitor Abemaciclib in Patients With NUT Carcinoma, Breast Cancer and Other Solid Tumors

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 45 (estimated)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 12 Years
• Healthy volunteers: Not accepted

Summary

This phase I trial tests the safety, side effects, and best dose of ZEN003694 when given together with abemaciclib in treating patients with NUT carcinoma, breast cancer or other solid tumors that have spread from where it first started (primary site) to other places in the body (metastatic) or cannot be removed by surgery (unresectable). ZEN003694 is an inhibitor of a family of proteins called the bromodomain and extra-terminal (BET). It may prevent the growth of tumor cells that overproduce BET protein. Abemaciclib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving ZEN003694 and abemaciclib may help shrink or stabilize cancer in patients with NUT carcinoma, breast cancer or other solid tumors.

Detailed description

PRIMARY OBJECTIVE: I. Determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of the combination of BET bromodomain inhibitor ZEN-3694 (ZEN003694) and abemaciclib. SECONDARY OBJECTIVES: I. To observe and record anti-tumor activity. II. Determine the preliminary rates of progression-free survival (PFS), overall survival (OS), overall response rate (ORR), time to response (TTR) and duration of response (DoR) for the combination of ZEN003694 and abemaciclib in participants utilizing Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. III. Evaluate the pharmacokinetic (PK) profile of the combination. EXPLORATORY OBJECTIVE: I. Explore potential biomarker indicators of response and resistance in tumor tissue and blood samples. OUTLINE: This is a dose-escalation study of BET bromodomain inhibitor ZEN-3694 followed by a dose expansion study. Patients receive ZEN003694 orally (PO) once daily (QD) on days 1-28 or 5 days on and 2 days off of each cycle, and abemaciclib PO twice daily (BID) on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo imaging evaluation, blood sample collection and tumor biopsy throughout the study. After completion of study treatment, patients are followed up for 30 days, every 3 months for 2 years, and then every 6 months for 3 years.

Conditions

• Anatomic Stage III Breast Cancer AJCC v8
• Anatomic Stage IV Breast Cancer AJCC v8
• Metastatic Breast Carcinoma
• Metastatic Malignant Solid Neoplasm
• Metastatic NUT Carcinoma
• Unresectable Breast Carcinoma
• Unresectable Malignant Solid Neoplasm
• Unresectable NUT Carcinoma

Interventions

Type	Name	Description
DRUG	Abemaciclib	Given PO
DRUG	BET Bromodomain Inhibitor ZEN-3694	Given PO
PROCEDURE	Biopsy Procedure	Undergo biopsy
PROCEDURE	Biospecimen Collection	Undergo blood sample collection
PROCEDURE	Diagnostic Imaging Testing	Undergo imaging evaluation

Timeline

• Start date: 2023-08-10
• Primary completion: 2026-06-01
• Completion: 2026-06-01
• First posted: 2022-05-13
• Last updated: 2026-04-13

Locations

7 sites across 1 country: United States

Regulatory

• FDA-regulated drug study