RecruitingInterventionalPhase 3

A Randomized, Open-label Phase 3 Study of Amivantamab and mFOLFOX6 or FOLFIRI Versus Cetuximab and mFOLFOX6 or FOLFIRI as First-line Treatment in Participants With KRAS/NRAS and BRAF Wild-type Unresectable or Metastatic Left-sided Colorectal Cancer

NCT ID: NCT06662786Sponsor: Janssen Research & Development, LLCLast updated: 2026-06-05

Summary

The purpose of this study is to compare how long the participants are disease-free (progression-free survival) when treated with amivantamab and chemotherapy with 5-fluorouracil, leucovorin calcium (folinic acid) or levoleucovorin, oxaliplatin (mFOLFOX6) or 5-fluorouracil, leucovorin calcium (folinic acid) or levoleucovorin, and irinotecan hydrochloride (FOLFIRI) versus cetuximab and mFOLFOX6 or FOLFIRI in adult participants with Kirsten rat sarcoma viral oncogene homolog (KRAS)/ Neuroblastoma RAS viral oncogene homolog (NRAS) and v-Raf murine sarcoma viral oncogene homolog B1 (BRAF) wild type (WT) unresectable or metastatic left-sided colorectal cancer.

Arms & interventions

BiologicalAmivantamab
Amivantamab will be administered.
BiologicalCetuximab
Cetuximab will be administered.
Drug5-fluorouracil
5-fluorouracil will be administered as chemotherapy regimen.
DrugLeucovorin calcium/Levoleucovorin
Leucovorin calcium/Levoleucovorin will be administered as chemotherapy regimen.
DrugOxaliplatin
Oxaliplatin will be administered as chemotherapy regimen.
DrugIrinotecan Hydrochloride
Irinotecan hydrochloride will be administered as chemotherapy regimen.

Outcome measures

Primary

Progression-Free Survival (PFS) as Assessed by Blinded Independent Central Review (BICR)
PFS is defined as the time from randomization until the date of objective disease progression or death (due to any cause), whichever comes first, as assessed by BICR using response evaluation criteria in solid tumors (RECIST) version (v) 1.1. Participants who have not progressed or have not died at the time of analysis will be censored at their last evaluable RECIST v1.1 assessment date.
Time frame: Up to 4 years and 2 months

Secondary

Overall Survival (OS)
Time frame: Up to 7 Years 3 Months
Objective Response Rate (ORR) as Assessed by BICR
Time frame: Up to 7 Years 3 Months
Objective Response Rate (ORR) as Assessed by Investigator
Time frame: Up to 7 Years 3 Months
Progression Free Survival (PFS) as Assessed by Investigator
Time frame: Up to 7 Years 3 Months
Duration of Response (DOR) as Assessed by BICR
Time frame: Up to 7 Years 3 Months
Duration of Response (DOR) as Assessed Investigator
Time frame: Up to 7 Years 3 Months
Time to Response (TTR) as Assessed by BICR
Time frame: Up to 7 Years 3 Months
Time to Response as Assessed by Investigator
Time frame: Up to 7 Years 3 Months
Progression-free Survival After Subsequent Therapy (PFS2)
Time frame: Up to 7 Years 3 Months
Disease Control Rate (DCR) as Assessed by BICR
Time frame: Up to 7 Years 3 Months
Disease Control Rate (DCR) as Assessed by Investigator
Time frame: Up to 7 Years 3 Months
Time to Treatment Failure
Time frame: Up to 7 Years 3 Months
Curative Resection (R0) Rate
Time frame: Up to 7 Years 3 Months
Number of Participants with Adverse Events (AEs) by Severity
Time frame: Up to 7 Years 3 Months
Number of Participants with Abnormalities in Laboratory Values
Time frame: Up to 7 Years 3 Months
Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Score
Time frame: From Baseline up to 7 Years 3 Months
Time to Worsening in Symptoms and Functioning as Measured by EORTC QLQ-C30
Time frame: Up to 7 Years 3 Months
Change from Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Colorectal Cancer Module 29 (EORTC-QLQ-C29) Score
Time frame: From Baseline up to 7 Years 3 Months
Time to Worsening in Symptoms and Functioning as Measured by EORTC QLQ-CR29
Time frame: Up to 7 Years 3 Months
Overall Side Effect Burden as Measured by European Organisation for Research and Treatment of Cancer (EORTC) Item 168 Scale Score
Time frame: Up to 7 Years 3 Months

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy volunteers: No

Inclusion Criteria: * Have histologically or cytologically confirmed adenocarcinoma of the left-sided colorectal cancer. Participants must have unresectable or metastatic disease * Determined to have Kirsten rat sarcoma viral oncogene (KRAS), neuroblastoma RAS viral oncogene homolog (NRAS), and v-raf murine sarcoma viral oncogene homolog B (BRAF) wild-type (WT) tumor by local and/or central testing (if available) * Must agree to the submission of fresh tumor tissue * Have measurable disease according to RECIST v1.1 * Has not received any prior systemic therapy for unresectable or metastatic colorectal cancer (CRC). Prior adjuvant/neoadjuvant therapy in the non-metastatic disease is permitted. However, the last course of adjuvant or neoadjuvant chemotherapy must have concluded greater than (\>) 12 months prior to CRC recurrence/metastases * Have an eastern cooperative oncology group (ECOG) performance status (PS) of 0 or 1 Exclusion Criteria: * Has medical history of (noninfectious) interstitial lung disease (ILD) /pneumonitis/pulmonary fibrosis or has current ILD/pneumonitis/pulmonary fibrosis, or where suspected ILD/pneumonitis/pulmonary fibrosis cannot be ruled out by imaging at screening * Has known allergies, hypersensitivity, or intolerance to excipients of any of the following: (a) amivantamab or cetuximab, (b) any component of mFOLFOX6 and, (c) any component of FOLFIRI * Has a prior or concurrent second malignancy other than the disease under study or one whose natural history or treatment is likely to interfere with any study endpoints of safety or the efficacy of the study treatment(s) * Participant with known mismatch repair deficiency (dMMR)/ high microsatellite instability (MSI-H) status and human epidermal growth factor receptor 2 (HER2)-positive/amplified tumor * Has prior exposure to any agents that target epidermal growth factor receptor (EGFR), mesenchymal epithelial transition (MET) or vascular endothelial growth factor (VEGF)

Study locations (79)

Banner MD Anderson Cancer Center

Gilbert, Arizona, 85234

Recruiting

St. Bernard's Medical Center

Jonesboro, Arkansas, 72401

Recruiting

Highlands Oncology Group

Springdale, Arkansas, 72762

Recruiting

CBCC Global Research

Bakersfield, California, 93309

Recruiting

Los Angeles Cancer Network

Glendale, California, 91204

Recruiting

Cancer and Blood Specialty Clinic

Los Alamitos, California, 90720

Recruiting

USC Norris Comprehensive Cancer Center

Los Angeles, California, 90033

Recruiting

UCLA

Santa Monica, California, 90404

Recruiting

Providence Medical Foundation

Santa Rosa, California, 95403

Recruiting

Torrance Memorial Physicians Network

Torrance, California, 90505

Recruiting

Rocky Mountain Cancer Centers

Denver, Colorado, 80218

Recruiting

Yale University School Of Medicine

New Haven, Connecticut, 06519

Recruiting

Georgetown Univ Medical Center Lombardi Cancer Center

Washington D.C., District of Columbia, 20007

Recruiting

Florida Cancer Specialists South

Fort Myers, Florida, 33901

Recruiting

AdventHealth Medical Group Oncology and Hematology at Orlando

Orlando, Florida, 32804

Recruiting

Florida Cancer Specialists North Region

St. Petersburg, Florida, 33701-4553

Recruiting

Florida Cancer Specialists East

West Palm Beach, Florida, 33401-3406

Recruiting

Grady Memorial Hospital

Atlanta, Georgia, 30303

Recruiting

Winship Cancer Institute Emory University

Atlanta, Georgia, 30322

Recruiting

Illinois Cancer Specialists

Arlington Heights, Illinois, 60005

Recruiting

Illinois CancerCare

Peoria, Illinois, 61615

Recruiting

Fort Wayne Medical Oncology & Hematology

Fort Wayne, Indiana, 46804

Recruiting

University of Iowa Hospital

Iowa City, Iowa, 52242

Recruiting

Mission Cancer Blood

Waukee, Iowa, 50263

Recruiting

Cancer Center of Kansas

Wichita, Kansas, 67214

Recruiting

Ochsner Clinic Foundation

New Orleans, Louisiana, 70121

Recruiting

MedStar Franklin Square Medical Center

Baltimore, Maryland, 21237

Recruiting

Frederick Health Hospital - James M Stockman Cancer Institute

Frederick, Maryland, 21702-4337

Recruiting

VA Ann Arbor Healthcare System

Ann Arbor, Michigan, 48105

Recruiting

University of Michigan

Ann Arbor, Michigan, 48109

Recruiting

Henry Ford Hospital

Detroit, Michigan, 48202

Recruiting

Start Midwest

Grand Rapids, Michigan, 49503

Recruiting

Hattiesburg Clinic

Hattiesburg, Mississippi, 39401

Recruiting

Washington University School Of Medicine

St Louis, Missouri, 63110

Recruiting

Nebraska Cancer Specialists Midwest Cancer Center

Omaha, Nebraska, 68130

Recruiting

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, 89169

Recruiting

Astera Cancer Care

East Brunswick, New Jersey, 08816

Recruiting

Rutgers Cancer Institute

New Brunswick, New Jersey, 08901

Recruiting

University of New Mexico Cancer Center

Albuquerque, New Mexico, 87102

Recruiting

Perlmutter Cancer Center at NYU Long Island

Mineola, New York, 11501

Recruiting

Mount Sinai

New York, New York, 10003

Recruiting

Mount Sinai West

New York, New York, 10009

Recruiting

NYU Langone Medical Center NYU Hematology Associates

New York, New York, 10016

Recruiting

Herbert Irving Comprehensive Cancer Center Columbia University Medical Center

New York, New York, 10032

Recruiting

New York Cancer and Blood Specialists

Shirley, New York, 11967

Recruiting

Montefiore Einstein Comprehensive Cancer Center

The Bronx, New York, 10461

Recruiting

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599

Recruiting

Gabrail Cancer Center

Canton, Ohio, 44718

Recruiting

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106

Recruiting

Cleveland Clinic Cancer Center Fairview Hospital Moll Pavilion

Cleveland, Ohio, 44111

Recruiting

Taussig Cancer Insititute Cleveland Clinic

Cleveland, Ohio, 44195

Recruiting

Cleveland Clinic Cancer Center Independence Family Health Center

Independence, Ohio, 44131

Recruiting

Cleveland Clinic Cancer Center Mansfield

Mansfield, Ohio, 44906

Recruiting

Cleveland Clinic Cancer Center Hillcrest Hospital

Mayfield Heights, Ohio, 44124

Recruiting

Cleveland Clinic Cancer Centers Sandusky

Sandusky, Ohio, 44870

Recruiting

Cleveland Clinic Cancer Center Strongsville

Strongsville, Ohio, 44136

Recruiting

Cleveland Clinic Cancer Center South Pointe Hospital

Warrensville Heights, Ohio, 44122

Recruiting

Wooster Milltown Specialty and Surgery Center

Wooster, Ohio, 44691

Recruiting

Oregon Health And Science University

Portland, Oregon, 97239

Recruiting

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107

Recruiting

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111

Recruiting

University Of Pittsburgh Medical Center UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232 1301

Recruiting

SCRI Oncology Partners

Nashville, Tennessee, 37203

Recruiting

Texas Oncology West Texas

Abilene, Texas, 79606

Recruiting

Texas Oncology DFW

Dallas, Texas, 75246

Recruiting

UT Southwestern

Dallas, Texas, 75390

Recruiting

MD Anderson Cancer Center

Houston, Texas, 77030

Recruiting

Baylor Scott and White Health 1

Round Rock, Texas, 78665

Recruiting

Texas Oncology - San Antonio

San Antonio, Texas, 78240

Recruiting

Baylor Scott and White Health

Temple, Texas, 76508

Recruiting

Virginia Cancer Specialists

Arlington, Virginia, 22201

Recruiting

Inova Schar Cancer Institute Dept of Fairfax Hospital

Fairfax, Virginia, 22031

Recruiting

Richmond VA Medical Center

Richmond, Virginia, 23249

Recruiting

VCU Massey Comprehensive Cancer Center

Richmond, Virginia, 23298

Recruiting

Swedish Cancer Institute Edmonds

Edmonds, Washington, 98026

Recruiting

Swedish Cancer Institute Issaquah

Issaquah, Washington, 98029

Recruiting

Swedish Cancer Institute

Seattle, Washington, 98104

Recruiting

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109

Recruiting

William S. Middleton Memorial VA

Madison, Wisconsin, 53705

Recruiting