Phase 1b2 Study of Adagrasib, Cetuximab, and Cemiplimab for Advanced KRAS G12C Mutated Metastatic Colorectal Cancer

What this Trial Is About

Researchers are evaluating a combination of three drugsadagrasib, cetuximab, and cemiplimabto see if they can help control metastatic colorectal cancer CRC that has a specific KRAS G12C mutation and has progressed after at least one prior chemotherapy treatment. This phase 1b2 study aims to determine the objective response rate, as well as other key outcomes like duration of response, progression-free survival, overall survival, and safety of this drug combination. The study also explores how tumors adapt to this treatment and seeks biomarkers that predict response or resistance. Participants will receive the study drugs in two phases a Lead-In phase where adagrasib dosing will be tested at different levels to find the recommended dose, followed by an Expansion phase where patients will receive adagrasib at the chosen dose along with cetuximab and cemiplimab. Adagrasib is taken orally, while cetuximab and cemiplimab are administered intravenously. The study includes mandatory tumor biopsies at baseline and during treatment to assess treatment effects. During the study, participants undergo various assessments including regular monitoring of safety and adverse events, tumor measurements, and laboratory tests to evaluate blood counts and organ function. The trial plans to follow participants through to study completion, averaging about one year, to collect data on treatment effectiveness and side effects. Participants must comply with study requirements including contraception use if applicable and attend scheduled visits for evaluations and biopsies.

A Multicenter Phase 1b/2 Study of Adagrasib, Cetuximab, and Cemiplimab for Metastatic Colorectal Cancer Harboring KRAS G12C Mutations