A Study of Amivantamab Monotherapy and in Addition to Standard-of-Care Chemotherapy in Participants With Advanced or Metastatic Colorectal Cancer

NCT ID: NCT05379595

Last Updated: 2025-11-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

225 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-07-29

Study Completion Date

2031-10-31

Brief Summary

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The purpose of this study is to assess the anti-tumor activity of amivantamab as a monotherapy (Cohorts A, B, and C), to assess the recommended phase 2 combination dose (RP2CD) of amivantamab when added to SoC chemotherapy (Ph1b cohorts) and to characterize the safety of amivantamab when added to standard-of care (SoC) chemotherapy in participants with metastatic colorectal cancer (mCRC) (Ph2 cohorts).

Detailed Description

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Colorectal cancer (CRC) is a major global health concern and the third most common cancer worldwide. Amivantamab (also known as RYBREVANT or JNJ-61186372) is a fully human immunoglobulin (Ig) G1-based bispecific antibody (Ab) directed against the epidermal growth factor (EGF) and mesenchymal epithelial transition (MET) receptors, with evidence of preclinical activity against non-small cell lung cancer (NSCLC) tumors with activating EGF receptor (EGFR) mutations, the T790M and C797S second-site resistance EGFR mutations, overexpressed wild-type EGFR, as well as with activation of the MET pathway. Amivantamab has demonstrated activity in both EGFR- and MET-driven NSCLC, with preclinical evidence demonstrating its ability to recruit immune effector cells. While two anti-EGFR antibodies are incorporated as part of the SoC for CRC patients, MET is highly expressed or amplified in subsets of CRC and additionally plays a role in mediating resistance to anti-EGFR treatments. The study consists of up to 28 days screening period, treatment period will begin on Cycle 1 Day 1 (C1D1) (for Cohorts A, B, and C) or C1D -2 (for Ph1b-D, Ph1b-E, Cohorts D, E and F) with the administration of the study treatment and continue as 28-day cycles until the end of treatment visit, up to 30 days after discontinuation of study treatment. The safety of amivantamab as a monotherapy or in addition to SoC chemotherapy will be assessed by physical examinations, Eastern Cooperative Oncology Group (ECOG) criteria for performance status (PS), laboratory tests, vital signs, monitoring of adverse events, and concomitant medication usage.

Conditions

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Advanced or Metastatic Colorectal Cancer

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Cohorts A, B, and C: Amivantamab Monotherapy

Participants with left-sided colorectal cancer (CRC) in Cohort A (no prior anti-epidermal growth factor receptor \[EGFR\] therapy) and in Cohort B (post anti-EGFR therapy), and right-sided CRC in Cohort C (with or without anti-EGFR therapy), will be administered intravenous (IV) infusion of amivantamab 1050 milligrams (mg) if body weight (BW) is less than (\<) 80 kilograms (kg) or 1400 mg if BW is greater than or equal to (\>=) 80 kg, as monotherapy on Days 1 and 15 of Cycle 2 (28-days cycle).

Group Type EXPERIMENTAL

Amivantamab IV

Intervention Type BIOLOGICAL

Amivantamab will be administered as intravenous infusion.

Cohorts Ph1b-D and D: Amivantamab+5-Fluorouracil, Leucovorin, and Oxaliplatin (mFOLFOX6)

Participants who are anti-EGFR treatment naïve, have not received oxaliplatin-based chemotherapy in the metastatic setting, will be administered IV infusion of amivantamab 1050 or 700 mg (dose level 0 \[DL0\]) if BW is \<80 kg, or 1400 or 1050 mg (dose de-escalation \[DL-1\]) if BW is \>= 80 kg, on Days -1, -2, 8 and 22 of Cycle 1 and along with mFOLFOX6 SOC chemotherapy on Days 1 and 15 of Cycle 1 and Days 1 and 15 of Cycle 2 (each cycle of 28 days) in Phase 1b dose confirmation Cohort (Cohort Ph1b-D). Participant in Phase 2 Cohort (Cohort D) will receive recommended Phase 2 combination dose (RP2CD) of amivantamab along with mFOLFOX6 SOC chemotherapy determined in Cohort Ph1b-D.

Group Type ACTIVE_COMPARATOR

Amivantamab IV

Intervention Type BIOLOGICAL

Amivantamab will be administered as intravenous infusion.

Fluorouracil

Intervention Type BIOLOGICAL

Fluorouracil will be administered as intravenous infusion.

Leucovorin

Intervention Type BIOLOGICAL

Leucovorin will be administered as intravenous infusion.

Oxaliplatin

Intervention Type BIOLOGICAL

Oxaliplatin will be administered as intravenous infusion.

Cohorts Ph1b-E and E: Amivantamab+5-Fluorouracil, Leucovorin, and Irinotecan (FOLFIRI)

Participants who are anti-EGFR treatment naïve, have not received irinotecan-based chemotherapy in the metastatic setting, will be administered IV infusion of Amivantamab along with FOLFIRI SOC chemotherapy on Days -1, -2, and 8 of Cycle 1 and Days 1 and 15 of Cycle 2 in Ph1b-E. For Cohort E, RP2CD determined in Ph1b-E will be administered.

Group Type ACTIVE_COMPARATOR

Amivantamab IV

Intervention Type BIOLOGICAL

Amivantamab will be administered as intravenous infusion.

Fluorouracil

Intervention Type BIOLOGICAL

Fluorouracil will be administered as intravenous infusion.

Leucovorin

Intervention Type BIOLOGICAL

Leucovorin will be administered as intravenous infusion.

Irinotecan

Intervention Type BIOLOGICAL

Irinotecan will be administered as intravenous infusion.

Cohort F: Amivantamab + mFOLFOX6

Participant who are treatment-naïve for right-sided unresectable or metastatic CRC. Participants will receive Amivantamab along with mFOLFOX6 SoC chemotherapy.

Group Type ACTIVE_COMPARATOR

Fluorouracil

Intervention Type BIOLOGICAL

Fluorouracil will be administered as intravenous infusion.

Leucovorin

Intervention Type BIOLOGICAL

Leucovorin will be administered as intravenous infusion.

Oxaliplatin

Intervention Type BIOLOGICAL

Oxaliplatin will be administered as intravenous infusion.

Amivantamab

Intervention Type BIOLOGICAL

Amivantamab will be administered.

Interventions

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Amivantamab IV

Amivantamab will be administered as intravenous infusion.

Intervention Type BIOLOGICAL

Fluorouracil

Fluorouracil will be administered as intravenous infusion.

Intervention Type BIOLOGICAL

Leucovorin

Leucovorin will be administered as intravenous infusion.

Intervention Type BIOLOGICAL

Oxaliplatin

Oxaliplatin will be administered as intravenous infusion.

Intervention Type BIOLOGICAL

Irinotecan

Irinotecan will be administered as intravenous infusion.

Intervention Type BIOLOGICAL

Amivantamab

Amivantamab will be administered.

Intervention Type BIOLOGICAL

Other Intervention Names

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RYBREVANT JNJ-61186372 JNJ-61186372 RYBREVANT

Eligibility Criteria

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Inclusion Criteria

* Participant must have been previously diagnosed with histologically or cytologically confirmed unresectable or metastatic adenocarcinoma of the colon or rectum
* Participant must have tumor previously characterized as having wild-type Kirsten rat sarcoma viral oncogene (KRAS), neuroblastoma RAS viral oncogene homolog (NRAS), v-raf murine sarcoma viral oncogene homolog B (BRAF), and without evidence of Erb-b2 receptor tyrosine kinase 2/human epidermal growth factor receptor 2 (ERBB2/HER2) amplification. Additional cohort-specific requirements:

* Phase (Ph) 2 (Cohorts A, B, and C) Amivantamab monotherapy: Participant must have received at least 2 but not more than 3 prior lines of systemic therapy in the metastatic setting. Participant must have been diagnosed with left-sided colorectal cancer (CRC) (Cohort A and B) and right-sided (Cohort C)and have received or been intolerant to standard of care (SoC) fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy and an anti-vascular endothelial growth factor (VEGF) treatment. Participant must be anti-EGFR treatment naive in Cohort A, an anti-epidermal growth factor receptor (EGFR) treatment Cohort B, with or without an anti-EGFR treatment in Cohort C
* Ph 1b Dose Confirmation Cohorts (Ph1b-D and Ph1b-E), Ph2 (Cohorts D and E) Amivantamab+mFOLFOX6/FOLFIRI: Participant must been diagnosed with CRC and have received no more than 1 prior line of systemic therapy in the metastatic setting. Cohort Ph1b-D/Cohort D: Participant must be anti-EGFR treatment naïve, have not received oxaliplatin-based chemotherapy in the metastatic setting, and be eligible for treatment with mFOLFOX6 according to local regulatory approvals and SoC guidelines. Cohort Ph1b-E/Cohort E: Participant must be anti-EGFR treatment naïve, have not received irinotecan-based chemotherapy in the metastatic setting, and be eligible for treatment with FOLFIRI according to local regulatory approvals and SoC guidelines
* Ph2 Cohorts F Amivantamab subcutaneous (SC) + mFOLFOX6: Participants must be treatment-naive for right-sided unresectable or metastatic CRC and be eligible for treatment with mFOLFOX6 according to local regulatory approvals and SoC guidelines
* For Phase 1 dose confirmation cohorts (Cohorts Ph1b-D and Ph1b-E): Participant must have evaluable disease. For Phase 2: Participant must have measurable disease according to Response Criteria in Solid Tumors (RECIST) Version 1.1. If only one measurable lesion exists, it may be used for the screening biopsy as long as baseline tumor assessment scans are performed greater than or equal to (\>=) 7 days after the biopsy
* Participant must have Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
* Participant must have a tumor lesion amenable for biopsy and agree to mandatory protocol-defined screening biopsy. Biopsies are required if clinically feasible for participants in Ph1b-D, Ph1b-E, and Cohort F. For Cohort F, archival tissue is required if a fresh biopsy is not feasible
* A female participant of childbearing potential must have a negative serum pregnancy test at screening and within 72 hours of the first dose of study treatment and must agree to further serum or urine pregnancy tests during the study. Note: Participant must not be pregnant, breastfeeding, or planning to become pregnant while enrolled in this study

Exclusion Criteria

* Cohorts A, B, C, Ph1b-D, D, Ph1b-E, and E: Participant with identified mutation in Kirsten rat sarcoma viral oncogene (KRAS), neuroblastoma RAS viral oncogene homolog (NRAS), v-raf murine sarcoma viral oncogene homolog B (BRAF), or epidermal growth factor receptor (EGFR) ectodomain, or ERBB2/HER2 amplification by central circulating tumor deoxyribonucleic acid (ctDNA) testing at screening; Cohort F: Participant with identified mutation in KRAS, NRAS, BRAF V600, or PTEN, identified fusions in ALK, ROS-1, RET, and NTRK 1, ERBB2/HER2 amplification, or identified to have MSI-H status by central ctDNA testing at screening
* Participant with symptomatic or untreated brain metastasis
* History or known presence of leptomeningeal disease
* Any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant (for example, compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Janssen Research & Development, LLC

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Janssen Research & Development, LLC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Research & Development, LLC

Locations

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O Neal Comprehensive Cancer Center at UAB

Birmingham, Alabama, United States

Site Status RECRUITING

University of Southern California

Los Angeles, California, United States

Site Status COMPLETED

University of California, Los Angeles UCLA

Los Angeles, California, United States

Site Status RECRUITING

Georgetown University Hospital

Washington D.C., District of Columbia, United States

Site Status RECRUITING

H Lee Moffitt Cancer Center

Tampa, Florida, United States

Site Status COMPLETED

University of Maryland School of Medicine

Baltimore, Maryland, United States

Site Status COMPLETED

University of Michigan Health System

Ann Arbor, Michigan, United States

Site Status RECRUITING

Start Midwest

Grand Rapids, Michigan, United States

Site Status RECRUITING

Hattiesburg Clinic

Hattiesburg, Mississippi, United States

Site Status RECRUITING

NYU Langone Long Island Clinical Research Associates

New York, New York, United States

Site Status RECRUITING

Herbert Irving Comprehensive Cancer Center Columbia University Medical Center

New York, New York, United States

Site Status RECRUITING

Stephenson Cancer Center

Oklahoma City, Oklahoma, United States

Site Status RECRUITING

Vanderbilt Ingram Cancer Center

Nashville, Tennessee, United States

Site Status RECRUITING

MD Anderson Cancer Center

Houston, Texas, United States

Site Status RECRUITING

Institut Jules Bordet

Anderlecht, , Belgium

Site Status RECRUITING

Cliniques Universitaires Saint Luc

Brussels, , Belgium

Site Status RECRUITING

UZ Antwerpen

Edegem, , Belgium

Site Status RECRUITING

Universitair Ziekenhuis Gasthuisberg

Leuven, , Belgium

Site Status RECRUITING

BC Cancer Agency - Vancouver BC

Vancouver, British Columbia, Canada

Site Status RECRUITING

The Ottawa Hospital Cancer Centre

Ottawa, Ontario, Canada

Site Status RECRUITING

Princess Margaret Cancer Centre University Health Network

Toronto, Ontario, Canada

Site Status RECRUITING

The Second Hospital To Dalian Medical University

Dalian, , China

Site Status COMPLETED

Sun Yat-sen University - The Sixth Affiliated Hospital Guangdong Gastrointestinal Hospital

Guangzhou, , China

Site Status RECRUITING

The Second Affiliated Hospital of Zhejiang University College of Medicine

Hangzhou, , China

Site Status RECRUITING

Hubei province tumor hospital

Wuhan, , China

Site Status RECRUITING

Asklepios Klinik Altona

Hamburg, , Germany

Site Status RECRUITING

Ludwig-Maximilians-Universitaet Muenchen

Munich, , Germany

Site Status RECRUITING

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, , Italy

Site Status RECRUITING

A O Ospedale Niguarda Ca Granda

Milan, , Italy

Site Status RECRUITING

Azienda Ospedaliero Universitaria Pisana

Pisa, , Italy

Site Status RECRUITING

University Malaya Medical Centre

Kuala Lumpur, , Malaysia

Site Status RECRUITING

Hospital Umum Sarawak

Kuching, , Malaysia

Site Status RECRUITING

Beacon Hospital Sdn Bhd

Petaling Jaya, , Malaysia

Site Status RECRUITING

Ad Vance Medical Research

Ponce, , Puerto Rico

Site Status RECRUITING

Pan American Center for Oncology Trials LLC

Rio Piedras, , Puerto Rico

Site Status RECRUITING

Seoul National University Hospital

Seoul, , South Korea

Site Status RECRUITING

Severance Hospital Yonsei University Health System

Seoul, , South Korea

Site Status RECRUITING

Asan Medical Center

Seoul, , South Korea

Site Status RECRUITING

Samsung Medical Center

Seoul, , South Korea

Site Status RECRUITING

The Catholic University of Korea Seoul St Mary s Hospital

Seoul, , South Korea

Site Status RECRUITING

Hosp Univ Vall D Hebron

Barcelona, , Spain

Site Status RECRUITING

Hosp. Gral. Univ. Gregorio Maranon

Madrid, , Spain

Site Status RECRUITING

Hosp. Univ. Ramon Y Cajal

Madrid, , Spain

Site Status RECRUITING

Hosp Univ Fund Jimenez Diaz

Madrid, , Spain

Site Status RECRUITING

Hosp Univ Hm Sanchinarro

Madrid, , Spain

Site Status RECRUITING

Hosp. Univ. Marques de Valdecilla

Santander, , Spain

Site Status RECRUITING

Hosp. Clinico Univ. de Valencia

Valencia, , Spain

Site Status RECRUITING

Changhua Christian Hospital

Changhua, , Taiwan

Site Status RECRUITING

Kaohsiung Chang Gung Memorial Hospital

Kaohsiung City, , Taiwan

Site Status RECRUITING

Chi Mei Medical Center Liu Ying

Liou Ying Township, , Taiwan

Site Status RECRUITING

National Cheng Kung University Hospital

Tainan, , Taiwan

Site Status RECRUITING

National Taiwan University Hospital

Taipei, , Taiwan

Site Status RECRUITING

Linkou Chang Gung Memorial Hospital

Taoyuan District, , Taiwan

Site Status RECRUITING

Countries

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France United Kingdom United States Belgium Canada China Germany Italy Malaysia Puerto Rico South Korea Spain Taiwan

Central Contacts

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Study Contact

Role: CONTACT

Phone: 844-434-4210

Email: [email protected]

Other Identifiers

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61186372GIC2002

Identifier Type: OTHER

Identifier Source: secondary_id

2021-006629-23

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2023-506517-22-00

Identifier Type: REGISTRY

Identifier Source: secondary_id

CR109215

Identifier Type: -

Identifier Source: org_study_id