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.

A 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

Colorectal Neoplasms

Metastatic Colorectal Cancer

Colorectal cancer

Anal cancer

Colon cancer

Rectal cancer

Gastrointestinal Cancer

Advanced Solid Tumors

Cancer

Advanced Solid Malignancies

Advanced Solid Tumor

Solid Tumor, Adult

Neoplasms

Adenocarcinoma

Advanced Stage Solid Tumors

Amivantamab

Oxaliplatin

Cetuximab

5-fluorouracil

Leucovorin calcium/Levoleucovorin

Irinotecan Hydrochloride

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

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.

OS is defined as the time from the date of randomization to the date of participant's
death due to any cause. Any participant not known to have died at the time of analysis
will be censored based on the last recorded date on which the participant was known to be
alive.

ORR is defined as the percentage of randomized participants achieving complete response
(CR) or partial response (PR), as determined by BICR using RECIST v1.1 criteria. On or
before the date of subsequent systemic anticancer therapy or date of curative-intent
procedure, whichever occurs first.

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 the
investigator. Participants who have not progressed or have not died at the time of
analysis will be censored at their last evaluable disease assessment date.

ORR is defined as the percentage of randomized participants achieving complete CR or PR,
as assessed by the investigator.

DOR is defined as time from the date of first documented response (CR or PR) until the
date of documented progression or death, whichever comes first, for participants who have
PR or CR, as assessed by BICR using RECIST v1.1 criteria.

DOR is defined as time from the date of first documented response (CR or PR) until the
date of documented progression or death, whichever comes first, for participants who have
PR or CR, as assessed by the investigator.

PFS2 is defined as the time from randomization until the date of second objective disease
progression, after initiation of subsequent anticancer therapy, based on investigator
assessment (after that used for PFS) or death, whichever comes first.

DCR is defined as the percentage of randomized participants achieving CR, PR, or stable
disease (with minimum duration of 7 weeks) as assessed by BICR using RECIST v1.1
criteria.

DCR is defined as the percentage of randomized participants achieving CR, PR, or stable
disease (with minimum duration of 7 weeks) as assessed by the investigator.

Time to treatment failure is defined as time from randomization to discontinuation of
therapy for any reason including death, progression, toxicity, or initiation of new
anticancer therapy.

Curative resection (R0) rate is defined as the percentage of the full analysis set who
underwent curative-intent surgery a where the residual tumor classification was R0.

An AE can be any unfavorable and unintended sign (including an abnormal finding),
symptom, or disease temporally associated with the use of a medicinal (investigational or
non-investigational) product, whether or not related to that medicinal (investigational
or non-investigational) product. AE severity will be graded according to the national
cancer institute common terminology criteria for adverse events (NCI-CTCAE) v5.0. by
using the standard grades as follows: Grade 1: Mild; asymptomatic or mild symptoms; Grade
2: Moderate; minimal, local or noninvasive intervention indicated; Grade 3: Severe or
medically significant but not immediately life threatening; hospitalization or
prolongation of hospitalization indicated; Grade 4: Life-threatening consequences; and
Grade 5: Death related to AE.

Participants with abnormalities in laboratory values (such as serum chemistry,
hematology) will be reported.

The EORTC QLQ-C30, is a self-administered, 30-item questionnaire measuring the
health-related quality of life (HRQoL) of participants with cancer. EORTC QLQ-C30
includes 5 functional scales, 3 symptom scales, a global health status / quality of life
scale, and 6 single items. Responses to items 1-28 are rated on a 4-point Likert response
scale ranging from 1 "Not at all" to 4 "Very much." Two global health status items are
rated on a 7-point numeric rating scale from 1 "Very Poor" to 7 "Excellent." Higher
scores indicate greater functioning, better global health status, and more severe
symptoms.

The EORTC QLQ-C30, is a self-administered, 30-item questionnaire measuring the HRQoL of
participants with cancer. EORTC QLQ-C30 includes 5 functional scales, 3 symptom scales, a
global health status / quality of life scale, and 6 single items. Responses to items 1-28
are rated on a 4-point Likert response scale ranging from 1 "Not at all" to 4 "Very
much." Two global health status items are rated on a 7-point numeric rating scale from 1
"Very Poor" to 7 "Excellent." Higher scores indicate greater functioning, better global
health status, and more severe symptom.

The EORTC QLQ-CR29, is a self-administered, 29-item questionnaire measuring the HRQoL of
participants with colorectal cancer. The QLQ CR29 includes items that evaluate symptoms
(gastrointestinal, urinary, pain, and others) and functional areas (sexual, body image,
weight, and anxiety) that are associated with colorectal cancer and its treatments.
Responses are rated on a 4-point Likert response scale ranging from 1 "Not at all" to 4
"Very much". All scores are linearly converted into a scale from 0 to 100. Higher scores
indicate greater functioning and more severe symptoms.

The EORTC item 168 is a single item used to measure the overall impact of treatment side
effects. Responses are rated on a 4-point Likert response scale ranging from 1 "not at
all" to 4 "very much." Higher scores indicate severe side effects.

Participants will receive amivantamab in combination with chemotherapy (mFOLFOX6
[chemotherapy consisting of 5-fluorouracil, leucovorin calcium (folinic acid) or
levoleucovorin, and oxaliplatin] or FOLFIRI [chemotherapy consisting of 5-fluorouracil,
leucovorin calcium (folinic acid) or levoleucovorin, and irinotecan hydrochloride]) for
28-days treatment cycles and will continue to receive the treatment until radiographic
disease progression or other discontinuation criteria are met.

Participants will receive cetuximab in combination with chemotherapy (mFOLFOX6 or
FOLFIRI) for 28-days treatment cycles and will continue to receive the treatment until
radiographic disease progression or other discontinuation criteria are met.

Banner MD Anderson Cancer Center

St. Bernard's Medical Center

CBCC Global Research

Los Angeles Cancer Network

Cancer and Blood Specialty Clinic

USC Norris Comprehensive Cancer Center

UCLA

Providence Medical Foundation

Torrance Memorial Physicians Network

Rocky Mountain Cancer Centers

Yale University School Of Medicine

Georgetown Univ Medical Center Lombardi Cancer Center

Florida Cancer Specialists South

AdventHealth Medical Group Oncology and Hematology at Orlando

Florida Cancer Specialists North Region

Florida Cancer Specialists East

Grady Memorial Hospital

Winship Cancer Institute Emory University

Fort Wayne Medical Oncology & Hematology

Ochsner Clinic Foundation

MedStar Franklin Square Medical Center

VA Ann Arbor Healthcare System

University of Michigan

Henry Ford Hospital

Hattiesburg Clinic

Washington University School Of Medicine

Nebraska Cancer Specialists Midwest Cancer Center

Comprehensive Cancer Centers of Nevada

Astera Cancer Care

Rutgers Cancer Institute

University of New Mexico Cancer Center

Perlmutter Cancer Center at NYU Long Island

Mount Sinai

Mount Sinai West

NYU Langone Medical Center NYU Hematology Associates

Herbert Irving Comprehensive Cancer Center Columbia University Medical Center

New York Cancer and Blood Specialists

Montefiore Einstein Comprehensive Cancer Center

University of North Carolina at Chapel Hill

University Hospitals Cleveland Medical Center

Cleveland Clinic Cancer Center Fairview Hospital Moll Pavilion

Taussig Cancer Insititute Cleveland Clinic

Cleveland Clinic Cancer Center Independence Family Health Center

Cleveland Clinic Cancer Center Mansfield

Cleveland Clinic Cancer Center Hillcrest Hospital

Cleveland Clinic Cancer Centers Sandusky

Cleveland Clinic Cancer Center Strongsville

Cleveland Clinic Cancer Center South Pointe Hospital

Wooster Milltown Specialty and Surgery Center

Thomas Jefferson University

Fox Chase Cancer Center

University Of Pittsburgh Medical Center UPMC Hillman Cancer Center

SCRI Oncology Partners

Texas Oncology West Texas

Texas Oncology DFW

MD Anderson Cancer Center

Texas Oncology - San Antonio

Baylor Scott and White Health

Virginia Cancer Specialists

Inova Schar Cancer Institute Dept of Fairfax Hospital

VCU Massey Comprehensive Cancer Center

Swedish Cancer Institute

William S. Middleton Memorial VA

Institut Jules Bordet

Universitair Ziekenhuis Antwerpen

AZ Maria Middelares

Hopital de Jolimont

Az Groeninge

Universitair Ziekenhuis Leuven

Centre Hospitalier Universitaire de Liege Domaine Universitaire du Sart Tilman

Fundacao Pio XII

Fundacao Universidade de Caxias do Sul

Fundacao Doutor Amaral Carvalho

Hospital Nossa Senhora da Conceicao S A

Hospital Santa Izabel Santa Casa de Misericordia da Bahia

Clinica de Hematologia e Oncologia Viver Ltda

Fundacao Faculdade Regional De Medicina S Jose Rio Preto Hospital De Base

Fundacao Faculdade de Medicina - Instituto do Cancer do Estado de Sao Paulo

Fundacao Antonio Prudente A C Camargo Cancer Center

Associacao Feminina de Educacao e Combate ao Cancer Hospital Santa Rita de Cassia

Arthur J E Child Comprehensive Cancer Centre

Ottawa Hospital

Princess Margaret Cancer Centre

Centre de Recherche du CHUM

Peking University First Hospital

Beijing Friendship Hospital Capital Medical University

Beijing Cancer Hospital

Peking University Third Hospital

The First Bethune Hospital of Jilin University

Hunan Cancer hospital

Sun Yat Sen University Cancer Center

The Sixth Affiliated Hospital Sun Yat sen University

Guangdong Provincial People's Hospital

The First Affiliated Hospital Zhejiang University College of Medicine

The Second Affiliated Hospital of Zhejiang University College of Medicine

Zhejiang Cancer Hospital

Harbin medical university cancer hospital

Huizhou Central People's Hospital

Illinois CancerCare

Praxis fur interdisziplinare Onkologie & Hamatologie GbR

Assuta MC

St James University Hospital

Karolinska Universitetssjukhuset

Oregon Health And Science University

Severance Hospital Yonsei University Health System

Seoul National University Hospital

National Taiwan University Hospital

Dr Abdurrahman Yurtaslan Oncology Training and Research Hospital

Hopital Prive Jean Mermoz

Hopital Claude Huriez

West China Hospital of Sichuan University

Hopital Saint Antoine

Rambam Medical Center

Hospital Pulau Pinang

Bialostockie Centrum Onkologii im Marii Sklodowskiej Curie w Bialymstoku

Narodowy Instytut Onkologii im Marii Sklodowskiej Curie Panstwowy Instytut BadawczyOddz w Gliwicach

Hosp. Gral. Univ. Gregorio Maranon

Sahlgrenska University Hospital

Sodersjukhuset

Ankara Bilkent Sehir Hastanesi

Marmara Universitesi Pendik Egitim ve Arastirma Hastanesi

Universitatsmedizin der Johannes Gutenberg Universitat Mainz

Istituto Dei Tumori Di Milano

Kaohsiung Medical University Chung Ho Memorial Hospital

Gabrail Cancer Center

SPZOZ Opolskie Centrum Onkologii im. Prof. Tadeusza Koszarowskiego

First Hospital of Shanxi Medical University

Istituto Clinico Humanitas

SPZOZ Ministerstwa Spraw Wewnetrznych z Warminsko Mazurskim Centrum Onkologii w Olsztynie

Clinica Univ. de Navarra

Hosp. Univ. 12 de Octubre

Peking University Shenzhen Hospital

Hospital Kuala Lumpur

National Cancer Center Hospital

Antoni van Leeuwenhoek

Gazi Universitesi Hastanesi

Kaohsiung Chang Gung Memorial Hospital

Fudan University Shanghai Cancer Center

Yitzhak Shamir Medical Center

University Malaya Medical Centre

Szpital Specjalistyczny w Brzozowie Podkarpacki Osrodek Onkologiczny im Ks B Markiewicza

A 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

Trials at a glance

Trials at a glance

A 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

Outcome measures

Primary outcome measures

Secondary outcome measures