Testing the Addition of Anti-cancer Drug, ZEN003694, to the Usual Chemotherapy Treatment, Cetuximab Plus Encorafenib, for Colorectal Cancer

Summary

This phase I trial tests the safety, best dose, and effectiveness of ZEN003694 in combination with cetuximab and encorafenib in treating patients with colorectal cancer that has not responded to previous treatment (refractory), that has come back after a period of improvement (relapsed), and that has spread from where it first started (primary site) to other places in the body (metastatic). ZEN003694 is a protein inhibitor that binds to BET proteins. When ZEN003694 binds to BET proteins, it disrupts gene expression. Preventing the expression of certain growth-promoting genes may inhibit proliferation of tumor cells that over-express BET proteins. Immunotherapy with monoclonal antibodies, such as cetuximab, may help the body's immune system attack the tumor, and may interfere with the ability of tumor cells to grow and spread. Encorafenib is an enzyme inhibitor. It inhibits pathways that are responsible for controlling cell proliferation and survival, which may lead to a decrease in tumor cell proliferation. Both cetuximab and encorafenib have been approved to treat cancer. Adding ZEN003694 to cetuximab and encorafenib may be more effective at treating patients with refractory metastatic colorectal cancer than giving the usual treatment (cetuximab and encorafenib) alone.

Timeline

Start

2024-06-05

Primary completion

2027-01-30

Completion

2027-01-30

Publications

• Lee HM, Zheng Z, Sorokin A, Wong CW, Napolitano S, Chowdhury S, Kanikarla PM, Singh AK, Kochat V, Bristow CA, Srinivasan S, Peoples M, Arslan E, Alshenaifi JY, Villarreal OE, Morris VK, Shen JP, Meric-Bernstam F, Jain AK, Fowlkes NW, Anderson A, Menter DG, Saw AK, Rai K, Kopetz S. Reprogramming of Cellular Plasticity via ETS and MYC Core-regulatory Circuits During Response to MAPK Inhibition in BRAF-mutant Colorectal Cancer. Clin Cancer Res. 2026 May 8. doi: 10.1158/1078-0432.CCR-25-4370. Online ahead of print.
• Lee HM, Zheng Z, Sorokin A, Wong CW, Napolitano S, Chowdhury S, Kanikarla PM, Singh AK, Kochat V, Bristow CA, Srinivasan S, Peoples M, Arslan E, Alshenaifi JY, Villarreal OE, Morris VK, Shen JP, Meric-Bernstam F, Jain AK, Fowlkes NW, Anderson A, Menter DG, Saw AK, Rai K, Kopetz S. Reprogramming of Cellular Plasticity via ETS and MYC Core-regulatory Circuits During Response to MAPK Inhibition in BRAF-mutant Colorectal Cancer. bioRxiv [Preprint]. 2025 Jun 20:2025.06.15.659716. doi: 10.1101/2025.06.15.659716.

Drugs

Indications