Purpose

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

Condition

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • Participant must have been previously diagnosed with histologically or cytologically confirmed unresectable or metastatic adenocarcinoma of the colon or rectum - For Phase 1 dose confirmation cohorts (Cohorts Ph1b-D and Ph1b-E): Participant must have evaluable disease. For Phase 2 dose expansion cohorts (Cohorts D and E): 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 - 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

  • 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 - 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

Phase
Phase 1/Phase 2
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
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).
  • Drug: Amivantamab
    Amivantamab will be administered as intravenous infusion.
    Other names:
    • RYBREVANT
    • JNJ-61186372
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.
  • Drug: Amivantamab
    Amivantamab will be administered as intravenous infusion.
    Other names:
    • RYBREVANT
    • JNJ-61186372
  • Biological: Fluorouracil
    Fluorouracil will be administered as intravenous infusion.
  • Biological: Leucovorin
    Leucovorin will be administered as intravenous infusion.
  • Biological: Oxaliplatin
    Oxaliplatin will be administered as intravenous infusion.
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.
  • Drug: Amivantamab
    Amivantamab will be administered as intravenous infusion.
    Other names:
    • RYBREVANT
    • JNJ-61186372
  • Biological: Fluorouracil
    Fluorouracil will be administered as intravenous infusion.
  • Biological: Leucovorin
    Leucovorin will be administered as intravenous infusion.
  • Biological: Irinotecan
    Irinotecan will be administered as intravenous infusion.

Recruiting Locations

O Neal Comprehensive Cancer Center at UAB
Birmingham, Alabama 35233

More Details

Status
Recruiting
Sponsor
Janssen Research & Development, LLC

Study Contact

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

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 and E) 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. The total duration of this study will be up to 4 years 3 months.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.