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.~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, 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 also under a tumor biopsy at baseline, days 1-8 of cycle 2, and at off-treatment. Patients undergo imaging evaluation at baseline, every 2 cycles or 8 weeks, and at off-treatment.~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.
This phase I trial tests the safety, side effects, and best dose of a ZEN003694 when given together with abemaciclib in treating patients with NUT carcinoma or other solid tumors that have spread 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 or other solid tumors.