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

NCT05379595 | Recruiting Phase 1 FDA Drug

• 4 other identifiers: CR10921561186372GIC20022021-006629-232023-506517-22-00
• Study Type: interventional
• Target: 225
• Locations: 11 countries
• Sites: 53

Brief 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).

Conditions

Advanced or Metastatic Colorectal Cancer

Outcome Measures

Primary Outcomes (9)

• Cohorts A, B, and C: Objective Response Rate (ORR)

  ORR is defined as the percentage of participants who achieve either a partial response (PR) or complete response (CR), as defined by investigator assessment using Response Criteria in Solid Tumors (RECIST) version 1.1.

  Up to 4 years 3 months

• Cohorts Ph1b-D and Ph1b-E: Number of Participants with Dose-limiting Toxicity (DLT)

  Number of participants with DLT will be assessed. The DLTs are specific adverse events and are defined as any of the following: high grade non-hematologic toxicity, or hematologic toxicity.

  Up to 4 years 3 months

• Cohorts Ph1b-D and Ph1b-E: Number of Participants with DLT by Severity

  Number of participants with DLT by severity will be assessed. The DLTs are specific adverse events and are defined as any of the following: high grade non-hematologic toxicity, or hematologic toxicity. Toxicities will be graded for severity according to the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0, graded as Grade 1: mild, Grade 2: moderate, Grade 3: severe, Grade 4: life-threatening, and Grade 5: death related to adverse event.

  Up to 4 years 3 months

• Cohorts D and E: Number of Participants with Adverse Events (AE)

  An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/ biological agent under study. Severity of AEs will be graded according to the NCI CTCAE version 5.0. Severity scale ranges from Grade 1 (Mild) to Grade 5 (Death). Grade 1: mild, Grade 2: moderate, Grade 3: severe, Grade 4: life-threatening and Grade 5: death related to adverse event.

  Up to 4 years 3 months

• Cohorts D and E: Number of Participants with Laboratory Values Abnormalities

  Number of participants with laboratory values abnormalities, which includes serum chemistry, hematology, coagulation, and urinalysis, will be reported.

  Up to 4 years 3 months

• Cohorts D and E: Number of Participants with Vital Signs Abnormalities

  Number of participants with vital signs including temperature, heart rate, respiratory rate, and blood pressure (systolic and diastolic) and oxygen saturation, abnormalities will be reported.

  Up to 4 years 3 months

• Cohorts F: Number of Participants with Adverse Events (AE)

  An AE is any untoward medical occurrence in a participant taking part in a in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/ biological agent under study. Severity of AEs will be graded according to the NCI-CTCAE version 5.0. Severity scale ranges from Grade 1 (Mild) to Grade 5 (Death). Grade 1: mild, Grade 2: moderate, Grade 3: severe, Grade 4: life-threatening and Grade 5: death related to adverse event.

  Up to 4 years 3 months

• Cohorts F: Number of Participants with Laboratory Values Abnormalities

  Number of participants with laboratory values abnormalities, which includes serum chemistry, hematology, coagulation, and urinalysis, will be reported.

  Up to 4 years 3 months

• Cohorts F: Number of Participants with Vital Signs Abnormalities

  Number of participants with vital signs including temperature, heart rate, respiratory rate, and blood pressure (systolic and diastolic) and oxygen saturation, abnormalities will be reported.

  Up to 4 years 3 months

Secondary Outcomes (8)

• Cohorts A, B, C, Ph1b-D, and Ph1b-E: Number of Participants with AEs

  Up to 4 years 3 months

• Cohorts A, B, C, Ph1b-D, and Ph1b-E: Number of Participants with Laboratory Values Abnormalities

  Up to 4 years 3 months

• Cohorts A, B, C, Ph1b-D, and Ph1b-E: Number of Participants with Vital Signs Abnormalities

  Up to 4 years 3 months

• Cohorts Ph1b-D, Ph1b-E, D, E and F: ORR

  Up to 4 years 3 months

• Cohorts Ph1b-D, Ph1b-E, D, E and F: Duration of Response (DoR)

  Up to 4 years 3 months

Study Arms (4)

Cohorts A, B, and C: Amivantamab Monotherapy

EXPERIMENTAL

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).

Biological: Amivantamab IV

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

ACTIVE COMPARATOR

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.

Biological: Amivantamab IV; Biological: Fluorouracil; Biological: Leucovorin; Biological: Oxaliplatin

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

ACTIVE COMPARATOR

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.

Biological: Amivantamab IV; Biological: Fluorouracil; Biological: Leucovorin; Biological: Irinotecan

Cohort F: Amivantamab + mFOLFOX6

ACTIVE COMPARATOR

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

Biological: Fluorouracil; Biological: Leucovorin; Biological: Oxaliplatin; Biological: Amivantamab

Interventions

Amivantamab IV BIOLOGICAL

Amivantamab will be administered as intravenous infusion.

Also known as: RYBREVANT, JNJ-61186372

Cohorts A, B, and C: Amivantamab Monotherapy; Cohorts Ph1b-D and D: Amivantamab+5-Fluorouracil, Leucovorin, and Oxaliplatin (mFOLFOX6); Cohorts Ph1b-E and E: Amivantamab+5-Fluorouracil, Leucovorin, and Irinotecan (FOLFIRI)

Fluorouracil BIOLOGICAL

Fluorouracil will be administered as intravenous infusion.

Cohort F: Amivantamab + mFOLFOX6; Cohorts Ph1b-D and D: Amivantamab+5-Fluorouracil, Leucovorin, and Oxaliplatin (mFOLFOX6); Cohorts Ph1b-E and E: Amivantamab+5-Fluorouracil, Leucovorin, and Irinotecan (FOLFIRI)

Leucovorin BIOLOGICAL

Leucovorin will be administered as intravenous infusion.

Cohort F: Amivantamab + mFOLFOX6; Cohorts Ph1b-D and D: Amivantamab+5-Fluorouracil, Leucovorin, and Oxaliplatin (mFOLFOX6); Cohorts Ph1b-E and E: Amivantamab+5-Fluorouracil, Leucovorin, and Irinotecan (FOLFIRI)

Oxaliplatin BIOLOGICAL

Oxaliplatin will be administered as intravenous infusion.

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

Irinotecan BIOLOGICAL

Irinotecan will be administered as intravenous infusion.

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

Amivantamab BIOLOGICAL

Amivantamab will be administered.

Also known as: JNJ-61186372, RYBREVANT

Cohort F: Amivantamab + mFOLFOX6

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (53)

O Neal Comprehensive Cancer Center at UAB

Birmingham, Alabama, 35233, United States

RECRUITING

University of Southern California

Los Angeles, California, 90033, United States

COMPLETED

University of California, Los Angeles UCLA

Los Angeles, California, 90404, United States

RECRUITING

Georgetown University Hospital

Washington D.C., District of Columbia, 20007, United States

RECRUITING

H Lee Moffitt Cancer Center

Tampa, Florida, 33612, United States

COMPLETED

University of Maryland School of Medicine

Baltimore, Maryland, 21201, United States

COMPLETED

University of Michigan Health System

Ann Arbor, Michigan, 48103, United States

RECRUITING

Start Midwest

Grand Rapids, Michigan, 49546, United States

RECRUITING

Hattiesburg Clinic

Hattiesburg, Mississippi, 39401, United States

RECRUITING

NYU Langone Long Island Clinical Research Associates

New York, New York, 10016, United States

RECRUITING

Herbert Irving Comprehensive Cancer Center Columbia University Medical Center

New York, New York, 10032, United States

RECRUITING

Stephenson Cancer Center

Oklahoma City, Oklahoma, 73104, United States

RECRUITING

Vanderbilt Ingram Cancer Center

Nashville, Tennessee, 37232, United States

RECRUITING

MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Institut Jules Bordet

Anderlecht, 1070, Belgium

RECRUITING

Cliniques Universitaires Saint Luc

Brussels, 1200, Belgium

RECRUITING

UZ Antwerpen

Edegem, 2650, Belgium

RECRUITING

Universitair Ziekenhuis Gasthuisberg

Leuven, 3000, Belgium

RECRUITING

BC Cancer Agency - Vancouver BC

Vancouver, British Columbia, V5Z 4E6, Canada

RECRUITING

The Ottawa Hospital Cancer Centre

Ottawa, Ontario, K1H 8L6, Canada

RECRUITING

Princess Margaret Cancer Centre University Health Network

Toronto, Ontario, M5G 1X6, Canada

RECRUITING

The Second Hospital To Dalian Medical University

Dalian, 116023, China

COMPLETED

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

Guangzhou, 510655, China

RECRUITING

The Second Affiliated Hospital of Zhejiang University College of Medicine

Hangzhou, 310003, China

RECRUITING

Hubei province tumor hospital

Wuhan, 430079, China

RECRUITING

Asklepios Klinik Altona

Hamburg, 22763, Germany

RECRUITING

Ludwig-Maximilians-Universitaet Muenchen

Munich, 81377, Germany

RECRUITING

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, 20133, Italy

RECRUITING

A O Ospedale Niguarda Ca Granda

Milan, 20162, Italy

RECRUITING

Azienda Ospedaliero Universitaria Pisana

Pisa, 56126, Italy

RECRUITING

University Malaya Medical Centre

Kuala Lumpur, 59100, Malaysia

RECRUITING

Hospital Umum Sarawak

Kuching, 93586, Malaysia

RECRUITING

Beacon Hospital Sdn Bhd

Petaling Jaya, 46050, Malaysia

RECRUITING

Ad Vance Medical Research

Ponce, 00717, Puerto Rico

RECRUITING

Pan American Center for Oncology Trials LLC

Rio Piedras, 00935, Puerto Rico

RECRUITING

Seoul National University Hospital

Seoul, 03080, South Korea

RECRUITING

Severance Hospital Yonsei University Health System

Seoul, 03722, South Korea

RECRUITING

Asan Medical Center

Seoul, 05505, South Korea

RECRUITING

Samsung Medical Center

Seoul, 06351, South Korea

RECRUITING

The Catholic University of Korea Seoul St Mary s Hospital

Seoul, 06591, South Korea

RECRUITING

Hosp Univ Vall D Hebron

Barcelona, 08035, Spain

RECRUITING

Hosp. Gral. Univ. Gregorio Maranon

Madrid, 28007, Spain

RECRUITING

Hosp. Univ. Ramon Y Cajal

Madrid, 28034, Spain

RECRUITING

Hosp Univ Fund Jimenez Diaz

Madrid, 28040, Spain

RECRUITING

Hosp Univ Hm Sanchinarro

Madrid, 28050, Spain

RECRUITING

Hosp. Univ. Marques de Valdecilla

Santander, 39008, Spain

RECRUITING

Hosp. Clinico Univ. de Valencia

Valencia, 46010, Spain

RECRUITING

Changhua Christian Hospital

Changhua, 500, Taiwan

RECRUITING

Kaohsiung Chang Gung Memorial Hospital

Kaohsiung City, 83301, Taiwan

RECRUITING

Chi Mei Medical Center Liu Ying

Liou Ying Township, 736, Taiwan

RECRUITING

National Cheng Kung University Hospital

Tainan, 704, Taiwan

RECRUITING

National Taiwan University Hospital

Taipei, 10002, Taiwan

RECRUITING

Linkou Chang Gung Memorial Hospital

Taoyuan District, 33305, Taiwan

RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

amivantamab; Fluorouracil; Leucovorin; Oxaliplatin; Irinotecan

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Coordination Complexes; Organic Chemicals; Camptothecin; Alkaloids

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Central Study Contacts

Study Contact

CONTACT

844-434-4210; Participate-In-This-Study1@its.jnj.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 17, 2022
• First Posted: May 18, 2022
• Study Start: July 29, 2022
• Primary Completion (Estimated): April 27, 2027
• Study Completion (Estimated): October 31, 2030
• Last Updated: April 13, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

MY (3); IT (3); TW (6); DE (2); US (14); KR (5); CN (4); PR (2); CA (3); BE (4); ES (7)