RecruitingInterventionalPhase 3

A Randomized, Open-label Phase 3 Study of Amivantamab + FOLFIRI Versus Cetuximab/Bevacizumab + FOLFIRI in Participants With KRAS/NRAS and BRAF Wild-type Recurrent, Unresectable or Metastatic Colorectal Cancer Who Have Received Prior Chemotherapy

NCT ID: NCT06750094Sponsor: 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) and and the length of time until a participant dies (overall survival), when treated with amivantamab and chemotherapy with 5-fluorouracil, leucovorin calcium (folinic acid) or levoleucovorin, and irinotecan hydrochloride (FOLFIRI) versus either cetuximab or bevacizumab and FOLFIRI given to participants with Kirsten rat sarcoma viral oncogene/ neuroblastoma RAS viral oncogene homolog (KRAS/ NRAS) and v-raf murine sarcoma viral oncogene homolog B (BRAF) wild-type recurrent, unresectable or metastatic colorectal cancer who have previously received chemotherapy.

Arms & interventions

BiologicalAmivantamab
Amivantamab will be administered.
BiologicalCetuximab
Cetuximab will be administered.
BiologicalBevacizumab
Bevacizumab 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.
DrugIrinotecan
Irinotecan 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 2 years 1 month
Overall Survival (OS)
OS is defined as the time from the date of randomization to the date of participant's death due to any cause.
Time frame: Up to 4 years 4 months

Secondary

Objective Response Rate (ORR) as Assessed by BICR
Time frame: Up to 4 years 4 months
ORR as Assessed by Investigator
Time frame: Up to 4 years 4 months
Progression Free Survival as Assessed by Investigator
Time frame: Up to 4 years 4 months
Duration of Response (DoR) as Assessed by BICR
Time frame: Up to 4 years 4 months
Duration of Response as Assessed by Investigator
Time frame: Up to 4 years 4 months
Time to Response (TTR) as Assessed by BICR
Time frame: Up to 4 years 4 months
TTR as Assessed by Investigator
Time frame: Up to 4 years 4 months
Progression Free Survival After Subsequent Therapy (PFS2)
Time frame: Up to 4 years 4 months
Disease Control Rate (DCR) as Assessed by BICR
Time frame: Up to 4 years 4 months
Disease Control Rate as Assessed by Investigator
Time frame: Up to 4 years 4 months
Time to Treatment Failure
Time frame: Up to 4 years 4 months
Curative Resection (R0) Rate
Time frame: Up to 4 years 4 months
Number of Participants with Adverse Events (AEs) by Severity
Time frame: Up to 4 years 4 months
Number of Participants with Abnormalities in Laboratory Values
Time frame: Up to 4 years 4 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 4 years 4 months
Time to Worsening in Symptoms and Functioning as Measured by EORTC QLQ-C30
Time frame: Up to 4 years 4 months
Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-CR29) Score
Time frame: From baseline up to 4 years 4 months
Time to Worsening in Symptoms and Functioning as Measured by EORTC QLQ-CR29 Score
Time frame: Up to 4 years 4 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 4 years 4 months

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy volunteers: No

Inclusion Criteria: * Have histologically or cytologically confirmed adenocarcinoma of the colon or rectum. Participants must have recurrent, unresectable or metastatic disease * Determined to have kirsten rat sarcoma viral oncogene/neuroblastoma RAS viral oncogene homolog (KRAS/NRAS), G12, G13 and v-raf murine sarcoma viral oncogene homolog B (BRAF) V600X (X represents any single amino acid change from the original amino acid) wild type status by local and/or central next-generation sequencing (NGS) testing * Must agree to the submission of fresh or archival tumor tissue post progression from the most recent therapy, if clinically feasible * Have measurable disease according to response evaluation criteria in solid tumors (RECIST) version (v) 1.1 * Have an eastern cooperative oncology group (ECOG) performance status (PS) of 0 or 1 * Participant must have received 1 line of systemic therapy (fluoropyrimidine-based and oxaliplatin-based) for metastatic colorectal cancer (mCRC), with documented radiographic disease progression on or after this line of therapy. Participants can receive anti-VEGF as prior line of therapy 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: amivantamab, cetuximab or bevacizumab or 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 who has not received immunotherapy treatments * Participant with known human epidermal growth factor receptor 2 (HER2)- positive/amplified tumor * Has prior exposure to irinotecan, any agents that target epidermal growth factor receptor (EGFR) or mesenchymal epithelial transition (MET)

Study locations (70)

Ironwood Cancer and Research Center

Chandler, Arizona, 85224

Recruiting

Banner MD Anderson Cancer Center

Gilbert, Arizona, 85234

Recruiting

Arizona Oncology Associates PC NAHOA

Prescott, Arizona, 86301

Completed

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

University of Colorado Denver Anschultz Medical Campus

Aurora, Colorado, 80045

Recruiting

Rocky Mountain Cancer Centers

Denver, Colorado, 80218

Recruiting

Eastern Connecticut Hematology & Oncology Assoc.

Norwich, Connecticut, 06360

Recruiting

Florida Cancer Specialists South

Fort Myers, Florida, 33901

Recruiting

Mount Sinai Medical Center Campus

Miami Beach, Florida, 33140

Completed

AdventHealth Cancer Institute

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

University Cancer And Blood Center LLC

Athens, Georgia, 30607

Recruiting

Grady Memorial Hospital

Atlanta, Georgia, 30303

Recruiting

Piedmont Cancer Institute

Atlanta, Georgia, 30318

Recruiting

Winship Cancer Institute Emory University

Atlanta, Georgia, 30322

Recruiting

Illinois Cancer Specialists

Arlington Heights, Illinois, 60005

Recruiting

Illinois CancerCare

Peoria, Illinois, 61615

Recruiting

Franciscan Health

Indianapolis, Indiana, 46237

Recruiting

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242

Recruiting

Mission Cancer Blood

Waukee, Iowa, 50263

Recruiting

Cancer Center of Kansas

Wichita, Kansas, 67214

Recruiting

Mary Bird Perkins Cancer Center

Baton Rouge, Louisiana, 70809

Recruiting

MedStar Franklin Square Medical Center

Baltimore, Maryland, 21237

Recruiting

Frederick Health Hospital - James M Stockman Cancer Institute

Frederick, Maryland, 21702

Recruiting

University of Michigan Rogel Cancer Center

Ann Arbor, Michigan, 48109

Recruiting

Henry Ford Hospital

Detroit, Michigan, 48202

Recruiting

Cancer And Hematology Centers of Western Michigan PC

Grand Rapids, Michigan, 49503

Recruiting

Hattiesburg Clinic

Hattiesburg, Mississippi, 39401

Recruiting

Washington University School Of Medicine

St Louis, Missouri, 63110

Recruiting

Nebraska Cancer Specialists

Omaha, Nebraska, 68130

Recruiting

Astera Cancer Care

East Brunswick, New Jersey, 08816

Recruiting

Perlmutter Cancer Center at NYU Long Island

Mineola, New York, 11501

Recruiting

NYU Langone Medical Center NYU Hematology Associates

New York, New York, 10016

Recruiting

New York Cancer and Blood Specialists

Shirley, New York, 11967

Recruiting

Montefiore Einstein Comprehensive Cancer Center

The Bronx, New York, 10461

Recruiting

Gabrail Cancer Center

Canton, Ohio, 44718

Recruiting

University Hospital of Cleveland

Cleveland, Ohio, 44106

Recruiting

Oregon Health And Science University

Portland, Oregon, 97239

Recruiting

Alliance Cancer Specialists at Main Line

Penn Wynne, Pennsylvania, 19096

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

Tennessee Oncology Chattanooga

Chattanooga, Tennessee, 37404

Recruiting

SCRI Oncology Partners

Nashville, Tennessee, 37203

Recruiting

Tennessee Oncology

Nashville, Tennessee, 37203

Recruiting

Vanderbilt University Medical Center

Nashville, Tennessee, 37232

Recruiting

Texas Oncology West Texas

Abilene, Texas, 79606

Recruiting

Parkland Health and Hospital System

Dallas, Texas, 75235

Recruiting

Texas Oncology DFW

Dallas, Texas, 75246

Recruiting

UT Southwestern Medical Center

Dallas, Texas, 75390

Recruiting

MD Anderson Cancer Center

Houston, Texas, 77030

Recruiting

Baylor Scott & White Medical Center

Round Rock, Texas, 77845

Recruiting

Texas Oncology - San Antonio

San Antonio, Texas, 78240

Recruiting

Scott And White Memorial Hospital

Temple, Texas, 76508

Recruiting

UT Health East Texas HOPE Cancer Center

Tyler, Texas, 75701

Recruiting

Virginia Cancer Specialists

Arlington, Virginia, 22201

Recruiting

Richmond VA Medical Center

Richmond, Virginia, 23249

Recruiting

VCU Massey Comprehensive Cancer Center

Richmond, Virginia, 23298

Recruiting

Providence Regional Cancer System

Lacey, Washington, 98503

Recruiting

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109

Recruiting

Medical College Of Wisconsin

Milwaukee, Wisconsin, 53226

Recruiting