Recruiting
Phase 1
Phase 2

Amivantamab

Sponsor:

Janssen Research & Development, LLC

Code:

NCT05379595

Conditions

Advanced or Metastatic Colorectal Cancer

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Amivantamab IV

Fluorouracil

Leucovorin

Oxaliplatin

Irinotecan

Study Details

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

Study ID

NCT05379595

Start date

Jul 29, 2022

Status verified date

Aug, 2026

Completion date

Oct 31, 2030

Anticipated

Primary completion date

Apr 27, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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

Study Design

Enrollment

225 participants

Anticipated

Allocation

Non randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: 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).

active comparator: 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.

active comparator: 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.

active comparator: 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.

Interventions

Amivantamab IV

Amivantamab will be administered as intravenous infusion.

Fluorouracil

Fluorouracil will be administered as intravenous infusion.

Leucovorin

Leucovorin will be administered as intravenous infusion.

Oxaliplatin

Oxaliplatin will be administered as intravenous infusion.

Irinotecan

Irinotecan will be administered as intravenous infusion.

Amivantamab

Amivantamab will be administered.

Primary outcome measure

  • Cohorts A, B, and C: Objective Response Rate (ORR) [ Time Frame: Up to 4 years 3 months ]
  • Cohorts Ph1b-D and Ph1b-E: Number of Participants with Dose-limiting Toxicity (DLT) [ Time Frame: Up to 4 years 3 months ]
  • Cohorts Ph1b-D and Ph1b-E: Number of Participants with DLT by Severity [ Time Frame: Up to 4 years 3 months ]
  • Cohorts D and E: Number of Participants with Adverse Events (AE) [ Time Frame: Up to 4 years 3 months ]
  • Cohorts D and E: Number of Participants with Laboratory Values Abnormalities [ Time Frame: Up to 4 years 3 months ]
  • Cohorts D and E: Number of Participants with Vital Signs Abnormalities [ Time Frame: Up to 4 years 3 months ]
  • Cohorts F: Number of Participants with Adverse Events (AE) [ Time Frame: Up to 4 years 3 months ]
  • Cohorts F: Number of Participants with Laboratory Values Abnormalities [ Time Frame: Up to 4 years 3 months ]
  • Cohorts F: Number of Participants with Vital Signs Abnormalities [ Time Frame: Up to 4 years 3 months ]

Central Contacts and Locations

Central contacts

Study Contact

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

Locations

University of California, Los Angeles UCLA

Recruiting

Los Angeles, California, United States, 90404

University of Michigan Health System

Recruiting

Ann Arbor, Michigan, United States, 48103

Hattiesburg Clinic

Recruiting

Hattiesburg, Mississippi, United States, 39401

NYU Langone Long Island Clinical Research Associates

Recruiting

New York, New York, United States, 10016

Herbert Irving Comprehensive Cancer Center Columbia University Medical Center

Recruiting

New York, New York, United States, 10032

Vanderbilt Ingram Cancer Center

Recruiting

Nashville, Tennessee, United States, 37232

MD Anderson Cancer Center

Recruiting

Houston, Texas, United States, 77030

The Ottawa Hospital Cancer Centre

Recruiting

Ottawa, Ontario, Canada, K1H 8L6

Princess Margaret Cancer Centre University Health Network

Recruiting

Toronto, Ontario, Canada, M5G 1X6

More Information

Sponsor

Janssen Research & Development, LLC

Last update posted

Aug 28, 2026

Last verified

Aug, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by Janssen Research & Development, LLC on 2026-08-28.