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NCT05379595PHASE1, PHASE2Recruiting

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

Janssen Research & Development, LLC

Start Date

7/29/2022

Completion Date

10/31/2030

Summary

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

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.

Eligibility Criteria

Age Range: 18 years to No maximum

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

Interventions

BIOLOGICAL

Amivantamab IV

BIOLOGICAL

Fluorouracil

BIOLOGICAL

Leucovorin

BIOLOGICAL

Oxaliplatin

BIOLOGICAL

Irinotecan

BIOLOGICAL

Amivantamab

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Conditions

Advanced or Metastatic Colorectal Cancer

Locations

O Neal Comprehensive Cancer Center at UAB

Birmingham, Alabama 35233

United States

University of Southern California

Los Angeles, California 90033

United States

University of California, Los Angeles UCLA

Los Angeles, California 90404

United States

Georgetown University Hospital

Washington D.C., District of Columbia 20007

United States

H Lee Moffitt Cancer Center

Tampa, Florida 33612

United States

University of Maryland School of Medicine

Baltimore, Maryland 21201

United States

University of Michigan Health System

Ann Arbor, Michigan 48103

United States

Start Midwest

Grand Rapids, Michigan 49546

United States

Hattiesburg Clinic

Hattiesburg, Mississippi 39401

United States

NYU Langone Long Island Clinical Research Associates

New York, New York 10016

United States

Herbert Irving Comprehensive Cancer Center Columbia University Medical Center

New York, New York 10032

United States

Stephenson Cancer Center

Oklahoma City, Oklahoma 73104

United States

Vanderbilt Ingram Cancer Center

Nashville, Tennessee 37232

United States

MD Anderson Cancer Center

Houston, Texas 77030

United States

Institut Jules Bordet

Anderlecht, 1070

Belgium

Cliniques Universitaires Saint Luc

Brussels, 1200

Belgium

UZ Antwerpen

Edegem, 2650

Belgium

Universitair Ziekenhuis Gasthuisberg

Leuven, 3000

Belgium

BC Cancer Agency - Vancouver BC

Vancouver, British Columbia V5Z 4E6

Canada

The Ottawa Hospital Cancer Centre

Ottawa, Ontario K1H 8L6

Canada

Princess Margaret Cancer Centre University Health Network

Toronto, Ontario M5G 1X6

Canada

The Second Hospital To Dalian Medical University

Dalian, 116023

China

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

Guangzhou, 510655

China

The Second Affiliated Hospital of Zhejiang University College of Medicine

Hangzhou, 310003

China

Hubei province tumor hospital

Wuhan, 430079

China

Asklepios Klinik Altona

Hamburg, 22763

Germany

Ludwig-Maximilians-Universitaet Muenchen

Munich, 81377

Germany

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, 20133

Italy

A O Ospedale Niguarda Ca Granda

Milan, 20162

Italy

Azienda Ospedaliero Universitaria Pisana

Pisa, 56126

Italy

University Malaya Medical Centre

Kuala Lumpur, 59100

Malaysia

Hospital Umum Sarawak

Kuching, 93586

Malaysia

Beacon Hospital Sdn Bhd

Petaling Jaya, 46050

Malaysia

Ad Vance Medical Research

Ponce, 00717

Puerto Rico

Pan American Center for Oncology Trials LLC

Rio Piedras, 00935

Puerto Rico

Seoul National University Hospital

Seoul, 03080

South Korea

Severance Hospital Yonsei University Health System

Seoul, 03722

South Korea

Asan Medical Center

Seoul, 05505

South Korea

Samsung Medical Center

Seoul, 06351

South Korea

The Catholic University of Korea Seoul St Mary s Hospital

Seoul, 06591

South Korea

Hosp Univ Vall D Hebron

Barcelona, 08035

Spain

Hosp. Gral. Univ. Gregorio Maranon

Madrid, 28007

Spain

Hosp. Univ. Ramon Y Cajal

Madrid, 28034

Spain

Hosp Univ Fund Jimenez Diaz

Madrid, 28040

Spain

Hosp Univ Hm Sanchinarro

Madrid, 28050

Spain

Hosp. Univ. Marques de Valdecilla

Santander, 39008

Spain

Hosp. Clinico Univ. de Valencia

Valencia, 46010

Spain

Changhua Christian Hospital

Changhua, 500

Taiwan

Kaohsiung Chang Gung Memorial Hospital

Kaohsiung City, 83301

Taiwan

Chi Mei Medical Center Liu Ying

Liou Ying Township, 736

Taiwan

National Cheng Kung University Hospital

Tainan, 704

Taiwan

National Taiwan University Hospital

Taipei, 10002

Taiwan

Linkou Chang Gung Memorial Hospital

Taoyuan, 33305

Taiwan