Phase 3 Study of MRTX849 With Cetuximab vs Chemotherapy in Patients With Advanced Colorectal Cancer With KRAS G12C Mutation (KRYSTAL-10)

Study Overview
=================
Brief Summary
-----------------
Study 849-010 is an open-label, randomized Phase 3 clinical trial comparing the efficacy of MRTX849 administered in combination with cetuximab versus chemotherapy in the second-line treatment setting in patients with CRC with KRAS G12C mutation.

Official Title
-----------------
A Randomized Phase 3 Study of MRTX849 in Combination With Cetuximab Versus Chemotherapy in Patients With Advanced Colorectal Cancer With KRAS G12C Mutation With Disease Progression On or After Standard First-Line Therapy

Conditions
-----------------
Advanced Colorectal Cancer, Metastatic Colorectal Cancer

Intervention / Treatment
-----------------
* Drug: MRTX849
* Biological: Cetuximab
* Drug: mFOLFOX6 Regimen
* Drug: FOLFIRI Regimen


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histologically confirmed diagnosis of colorectal carcinoma with KRAS G12C mutation in tumor tissue. Prior receipt of 1st line treatment in advanced CRC with a fluoropyrimidine-based chemotherapy regimen containing either oxaliplatin or irinotecan, and radiographically documented progression of disease on or after treatment. Exclusion Criteria: Prior treatment with a therapy targeting KRAS G12C mutation (e.g., AMG 510). Prior treatment with an anti-EGFR antibody (e.g., cetuximab or panitumumab). Active brain metastasis

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MRTX849 + Cetuximab<br> | Drug: MRTX849<br>* 28 Day Cycle<br>Biological: Cetuximab<br>* 28 Day Cycle<br>* Other names: Erbitux;|
| Active Comparator: mFOLFOX6 or FOLFIRI<br> | Drug: mFOLFOX6 Regimen<br>* Fluorouracil Oxaliplatin Folinic acid<br>Drug: FOLFIRI Regimen<br>* Fluorouracil Irinotecan Folinic acid<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | Defined as time from date of randomization to date of death due to any cause. | 30 months | 
| Progression-free Survival (PFS) | Defined as time from randomization until disease progression or death from any cause, whichever occurs first. | 30 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events | Defined as number of patients with treatment emergent AEs. | 30 months | 
| Objective Response Rate (ORR) | Defined as the percent of patients documented to have a confirmed CR or PR. | 30 months | 
| Duration of Response (DOR) | Defined as the time from date of the first documentation of objective tumor response (CR or PR) to the first documentation of either Progression of Disease (PD) or death due to any cause, whichever occurs first. | 30 months | 
| Patient Reported Outcomes (PROs) | To be assessed by European Quality of Life Questionnaire for Cancer Patients (QLQ-C30). | 30 months | 
| Quality of Life Assessment | To be assessed by European Quality of Life Five Dimensions Questionnaire (EQ-5D-5L). | 30 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Colorectal Cancer, Colorectal Cancer Trial, Colorectal Carcinoma, Rectal Cancer, Colon Cancer, KRAS, KRAS G12C, RAS, Colorectal Adenocarcinoma