Testing the Combination of the Anti-cancer Drugs ZEN003694 (ZEN-3694) and Talazoparib in Patients With Advanced Solid Tumors, The ComBET Trial

Summary

This phase II trial tests whether ZEN003694 (ZEN-3694) in combination with talazoparib works to shrink tumors in patients with solid tumors that are unlikely to be cured or controlled with treatment and that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced). Another aim of this study is to find out if, and how, patients' genes influence their response to this specific drug combination. For this part of the study, investigators will run tests using samples of patients' tumor tissue and blood that will be collected during the study. ZEN-3694 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. Talazoparib is an inhibitor of PARP, an enzyme that helps repair deoxyribonucleic acid (DNA) when it becomes damaged. Blocking PARP may help keep cancer cells from repairing their damaged DNA, causing them to die. PARP inhibitors are a type of targeted therapy. Genes are pieces of the DNA code that individuals inherit from their parents. Some genes work to protect against cancer by correcting damage that can occur in the DNA when cells divide. BRCA1 and BRCA2 are two examples of these types of genes, and they are called tumor-suppressor genes. For example, if a person has a mutation in a BRCA1/2 gene they have a greatly increased risk of developing breast and ovarian cancer because their cells may no longer be able to completely repair damaged DNA. It is the accumulation of DNA damage which causes a cell to change into a cancerous cell. Other genes are also involved in this process, and these are called DNA damage repair genes. The KRAS mutation is a change in a protein in normal cells. Normally KRAS serves as an information hub for signals in the cell that lead to cell growth, but when there is a mutation in KRAS it signals too much and cells grow without being told to, which causes cancer. Combination therapy with ZEN-3694 and talazoparib may be effective at slowing or stopping tumor growth in patients with advanced cancer.

Conditions

• Advanced Malignant Solid Neoplasm
• Metastatic Malignant Solid Neoplasm
• Unresectable Malignant Solid Neoplasm

Interventions

DRUG

BET Bromodomain Inhibitor ZEN-3694

Given PO

PROCEDURE

Biopsy Procedure

Undergo tumor biopsy

PROCEDURE

Biospecimen Collection

Undergo blood sample collection

PROCEDURE

Diagnostic Imaging Testing

Undergo diagnostic imaging

DRUG

Talazoparib

Given PO

Sponsors & Collaborators

• National Cancer Institute (NCI)

  lead NIH

Principal Investigators

• Timothy A Yap · University of Texas MD Anderson Cancer Center LAO

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2022-11-14

Primary Completion

2026-12-31

Completion

2027-12-31

FDA Drug

Yes

Countries

• United States

Study Locations