National Cancer Institute (NCI)
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.
PRIMARY OBJECTIVES: I. To define the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of BET bromodomain inhibitor ZEN-3694 (ZEN003694) when used in combination with cetuximab and encorafenib. II. To define the safety profile of combination of ZEN003694, encorafenib, and cetuximab. SECONDARY OBJECTIVES: I. To observe and record anti-tumor activity. II. To evaluate clinical response signals of the combination. III. To assess the pharmacodynamic (PD) profile of the combination as defined by MAPK inhibition. IV. To assess the pharmacokinetics (PK) of ZEN003694 in combination…
Inclusion Criteria: * Patients must have histologically confirmed and radiographically measurable metastatic colorectal adenocarcinoma with known BRAF V600E mutation, confirmed in a Clinical Laboratory Improvement Amendments (CLIA) certified laboratory with at least one tumor measurable as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, and for which standard curative or palliative measures do not exist or are no longer effective * Age ≥ 18 years. Because no dosing or adverse event data are currently available on the use of ZEN003694 in combination with cetuximab…
Given PO
Undergo biopsy
Undergo collection of blood samples
Given IV
Undergo CT
Undergo ECHO
Given PO
Undergo MRI
Undergo MUGA