Stage IV Colorectal Cancer AJCC v8 Clinical Trial
Official title:
Open-Label Phase 1b/2 Study of Cetuximab Administered in Combination With LY3214996 (ERK 1/2 Inhibitor) or Cetuximab in Combination With LY3214996 and Abemaciclib in Patients With Metastatic, Anti-EGFR-Refractory Colorectal Cancer
This phase Ib/II trial investigates the side effects and best dose of LY3214996 when given together with cetuximab alone or in combination with abemaciclib and to see how well they work in treating patients with colorectal cancer that cannot be removed by surgery (unresectable) and/or has spread to other places in the body (metastatic). Cetuximab is a monoclonal antibody that may interfere with the ability of tumor cells to grow and spread. LY3214996 and abemaciclib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving LY3214996 and cetuximab alone or in combination with abemaciclib may help treat patients with colorectal cancer.
PRIMARY OBJECTIVES: I. Determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of ERK1/2 inhibitor LY3214996 (LY3214996) administered in combination with cetuximab. (Phase 1b) II. Determine the MTD and RP2D of LY3214996 administered in combination with cetuximab plus abemaciclib. (Phase 1b) III. Assess the preliminary antitumor activity of the treatment combinations based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. (Phase 2) SECONDARY OBJECTIVES: I. Assess the preliminary antitumor activity of the treatment combinations based on RECIST v.1.1. (Phase 1b) II. Characterize the safety profile of the treatment combinations (DLTs). III. Evaluate for pERK and Ki67 inhibition. EXPLORATORY OBJECTIVES: I. Assess blood- and tissue-based predictive biomarkers of activity and immune effects upon treatment with cetuximab, LY3214996, and abemaciclib. II. Demonstrate feasibility of establishing patient-derived xenograft (PDX) models in matched patients with cetuximab-refractory metastatic colorectal cancer (mCRC) to evaluate for biomarkers of response and mechanisms of resistance. III. Explore mechanisms of resistance to cetuximab plus LY3214996 and cetuximab, LY3214996, plus abemaciclib. OUTLINE: This is a phase Ib, dose-escalation study of ERK1/2 inhibitor LY3214996 followed by a phase II study. Patients are assigned to 1 of 2 arms. ARM A: Patients receive ERK1/2 inhibitor LY3214996 orally (PO) once daily (QD) on days 1-28 and cetuximab intravenously (IV) over 1-2 hours on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. ARM B: Patients receive ERK1/2 inhibitor LY3214996 and cetuximab as in Arm A. Patients also receive abemaciclib PO twice daily (BID) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 30 days. ;
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