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A Study of Amivantamab and FOLFIRI Versus Cetuximab/Bevacizumab and FOLFIRI in Participants With KRAS/NRAS and BRAF Wild-type Colorectal Cancer Who Have Previously Received Chemotherapy

RecruitingPhase 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

Who can join

Ages 18 and older · All sexes

Full eligibility criteria
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)

About the study

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.

What is being tested

Sponsor: Janssen Research & Development, LLC · Participants: 700 · Started: Dec 12, 2024

Contact the study team

Official record on ClinicalTrials.gov — NCT06750094

Locations in the U.S.

ArizonaIronwood Cancer and Research Center, Chandler
Banner MD Anderson Cancer Center, Gilbert
ArkansasSt. Bernard's Medical Center, Jonesboro
Highlands Oncology Group, Springdale
CaliforniaCBCC Global Research, Bakersfield
Los Angeles Cancer Network, Glendale
Cancer and Blood Specialty Clinic, Los Alamitos
USC Norris Comprehensive Cancer Center, Los Angeles
UCLA, Santa Monica
Providence Medical Foundation, Santa Rosa
Torrance Memorial Physicians Network, Torrance
ColoradoUniversity of Colorado Denver Anschultz Medical Campus, Aurora
Rocky Mountain Cancer Centers, Denver
FloridaFlorida Cancer Specialists South, Fort Myers
AdventHealth Cancer Institute, Orlando
Florida Cancer Specialists North Region, St. Petersburg
Florida Cancer Specialists East, West Palm Beach
GeorgiaUniversity Cancer And Blood Center LLC, Athens
Grady Memorial Hospital, Atlanta
Piedmont Cancer Institute, Atlanta
Winship Cancer Institute Emory University, Atlanta
IllinoisIllinois Cancer Specialists, Arlington Heights
Illinois CancerCare, Peoria
IndianaFranciscan Health, Indianapolis
IowaUniversity of Iowa Hospitals and Clinics, Iowa City
Mission Cancer Blood, Waukee
KansasCancer Center of Kansas, Wichita
LouisianaMary Bird Perkins Cancer Center, Baton Rouge
MarylandMedStar Franklin Square Medical Center, Baltimore
Frederick Health Hospital - James M Stockman Cancer Institute, Frederick
MichiganUniversity of Michigan Rogel Cancer Center, Ann Arbor
Henry Ford Hospital, Detroit
Cancer And Hematology Centers of Western Michigan PC, Grand Rapids
MississippiHattiesburg Clinic, Hattiesburg
MissouriWashington University School Of Medicine, St Louis
NebraskaNebraska Cancer Specialists, Omaha
New JerseyAstera Cancer Care, East Brunswick
New YorkPerlmutter Cancer Center at NYU Long Island, Mineola
NYU Langone Medical Center NYU Hematology Associates, New York
New York Cancer and Blood Specialists, Shirley
Montefiore Einstein Comprehensive Cancer Center, The Bronx
University of Buffalo Kaleida Health Cancer Care, Williamsville
OhioGabrail Cancer Center, Canton
University Hospital of Cleveland, Cleveland
OregonOregon Health And Science University, Portland
PennsylvaniaAlliance Cancer Specialists at Main Line, Penn Wynne
Fox Chase Cancer Center, Philadelphia
Thomas Jefferson University, Philadelphia
University Of Pittsburgh Medical Center UPMC Hillman Cancer Center, Pittsburgh
TennesseeTennessee Oncology Chattanooga, Chattanooga
SCRI Oncology Partners, Nashville
Tennessee Oncology, Nashville
Vanderbilt University Medical Center, Nashville
TexasTexas Oncology West Texas, Abilene
Parkland Health and Hospital System, Dallas
Texas Oncology DFW, Dallas
UT Southwestern Medical Center, Dallas
MD Anderson Cancer Center, Houston
Baylor Scott & White Medical Center, Round Rock
Texas Oncology - San Antonio, San Antonio
Scott And White Memorial Hospital, Temple
UT Health East Texas HOPE Cancer Center, Tyler
VirginiaVirginia Cancer Specialists, Arlington
Richmond VA Medical Center, Richmond
VCU Massey Comprehensive Cancer Center, Richmond
WashingtonProvidence Regional Cancer System, Lacey
Fred Hutchinson Cancer Research Center, Seattle
WisconsinMedical College Of Wisconsin, Milwaukee

Conditions

From ClinicalTrials.gov, data retrieved Sep 30, 2026. Each study sets its own eligibility; the study team decides who can join.