Neoplasms

Digestive System Diseases

All Conditions

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Antineoplastic Agents

All Drugs and Chemicals

Cetuximab

Cemiplimab

Adagrasib

Antineoplastic Agents, Immunological

Participants enrolled in the Lead-In phase, the dose of adagrasib participants receive will depend on when the participant join this study. The first group of participants will receive the starting dose level of adagrasib. If intolerable side effects are seen, a second group of participants will be enrolled to receive a lower dose. One (1) of these 2 doses will be chosen as the recommended dose of adagrasib.

Participants enrolled in the Expansion phase, participants will receive adagrasib at the recommended dose that was found in the Lead-In phase.

Christine Parseghian, MD

To learn if the drug combination of adagrasib, cetuximab, and cemiplimab can help to control metastatic CRC with KRAS G12C mutations.

Primary Objective

• To determine the objective response rate of the adagrasib, cetuximab, and cemiplimab combination for treatment of advanced KRAS G12C MT CRC that has progressed on at least one line of prior systemic chemotherapy.

Secondary Objectives

* To estimate duration of response (DOR), progression free survival (PFS), and overall survival (OS) for the combination of adagrasib, cetuximab, and cemiplimab in participants with advanced KRAS G12C MT CRC that has progressed on at least one line of prior systemic chemotherapy.
* To estimate the safety and tolerability of the combination of adagrasib, cetuximab, and cemiplimab in participants with advanced KRAS G12C MT CRC that has progressed on at least one line of prior systemic chemotherapy.

Exploratory Objectives

* To assess predictive biomarkers of response and resistance to the combination of adagrasib, cetuximab, plus cemiplimab.
* To assess mechanisms of tumor cell adaptation upon treatment with the combination of adagrasib, cetuximab, plus cemiplimab.
* To determine mechanisms of acquired resistance to the combination of adagrasib, cetuximab, plus cemiplimab.
* To assess the effect of the combination of adagrasib, cetuximab plus cemiplimab on the immune tumor microenvironment.
* To generate cell lines and participant derived xenograft (PDX) models from tumor samples.

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

Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0

M.D. Anderson Cancer Center

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
A Multicenter Phase 1b/2 Study of Adagrasib, Cetuximab, and Cemiplimab for Metastatic Colorectal Cancer Harboring KRAS G12C Mutations	NCT06412198	Metastatic Colo... KRAS G12C Mutat...	Cetuximab Cemiplimab Adagrasib	18 Years -	M.D. Anderson Cancer Center
A Multicenter Phase 1b/2 Study of Adagrasib, Cetuximab, and Cemiplimab for Metastatic Colorectal Cancer Harboring KRAS G12C Mutations	NCT06412198	Metastatic Colo... KRAS G12C Mutat...	Cetuximab Cemiplimab Adagrasib	18 Years -	M.D. Anderson Cancer Center

Spots Global Cancer Trial Database for kras g12c mutations