A Phase 1b/2, Open-Label Study of Amivantamab Monotherapy and in Addition to Standard-of-Care Chemotherapy in Participants With Advanced or Metastatic Colorectal Cancer
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.
Arms & interventions
- BiologicalAmivantamab IV
Amivantamab will be administered as intravenous infusion.
- BiologicalFluorouracil
Fluorouracil will be administered as intravenous infusion.
- BiologicalLeucovorin
Leucovorin will be administered as intravenous infusion.
- BiologicalOxaliplatin
Oxaliplatin will be administered as intravenous infusion.
- BiologicalIrinotecan
Irinotecan will be administered as intravenous infusion.
- BiologicalAmivantamab
Amivantamab will be administered.
Outcome measures
Primary
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Up to 4 years 3 months
Secondary
Cohorts A, B, C, Ph1b-D, and Ph1b-E: Number of Participants with AEs
Time frame: Up to 4 years 3 months
Cohorts A, B, C, Ph1b-D, and Ph1b-E: Number of Participants with Laboratory Values Abnormalities
Time frame: Up to 4 years 3 months
Cohorts A, B, C, Ph1b-D, and Ph1b-E: Number of Participants with Vital Signs Abnormalities
Time frame: Up to 4 years 3 months
Cohorts Ph1b-D, Ph1b-E, D, E and F: ORR
Time frame: Up to 4 years 3 months
Cohorts Ph1b-D, Ph1b-E, D, E and F: Duration of Response (DoR)
Time frame: Up to 4 years 3 months
Cohorts Ph1b-D, Ph1b-E, D, E and F: Disease Control Rate (DCR)
Time frame: Up to 4 years 3 months
Cohorts Ph1b-D, Ph1b-E, D, E and F: Clinical Benefit Rate (CBR)
Time frame: Up to 4 years 3 months
Cohorts D, E and F: Progression Free Survival (PFS)
Time frame: Up to 4 years 3 months
Eligibility criteria
Study locations (14)
O Neal Comprehensive Cancer Center at UAB
Birmingham, Alabama, 35233
University of Southern California
Los Angeles, California, 90033
University of California, Los Angeles UCLA
Los Angeles, California, 90404
Georgetown University Hospital
Washington D.C., District of Columbia, 20007
H Lee Moffitt Cancer Center
Tampa, Florida, 33612
University of Maryland School of Medicine
Baltimore, Maryland, 21201
University of Michigan Health System
Ann Arbor, Michigan, 48103
Start Midwest
Grand Rapids, Michigan, 49546
Hattiesburg Clinic
Hattiesburg, Mississippi, 39401
NYU Langone Long Island Clinical Research Associates
New York, New York, 10016
Herbert Irving Comprehensive Cancer Center Columbia University Medical Center
New York, New York, 10032
Stephenson Cancer Center
Oklahoma City, Oklahoma, 73104
Vanderbilt Ingram Cancer Center
Nashville, Tennessee, 37232
MD Anderson Cancer Center
Houston, Texas, 77030
References
- Oberstein PE, Hecht JR, Raghav K, Pietrantonio F, Arnold D, Moreno V, Van Cutsem E, Malik RA, Hong YS, Lee MA, Yu-Li Su H, Lee J, Chandana S, Cruz-Correa M, Yuan Y, Ahmad A, Lai KM, Hsu HC, Chen EX, Elez E, Lin CC, Lopez C, Prenen H, Rosello-Keranen S, Velez H, Yeh YM, Heinemann V, Eng C, Beom SH, Tejpar S, Chowdhury S, Lyu X, Kamat M, Curtin JC, Patel B, Xie J, Bhattacharya R, Schnepp RW, Yilmaz E, Iwasawa R, Daksh M, Lorenzini P, Thayu M, Baig M, Kim HS, Han SW. Amivantamab Monotherapy in Chemorefractory RAS/BRAF Wild-Type Metastatic Colorectal Cancer: Results From OrigAMI-1, an Open-Label, Phase Ib/II Study. J Clin Oncol. 2026 Apr 21:JCO2502187. doi: 10.1200/JCO-25-02187. Online ahead of print.(PubMed)