Amivantamab Monotherapy in Chemorefractory <i>RAS</i> / <i>BRAF</i> Wild-Type Metastatic Colorectal Cancer: Results From OrigAMI-1, an Open-Label, Phase Ib/II Study

PURPOSE: Amivantamab, an EGFR-MET bispecific antibody with immune cell-directing activity, is approved in non-small cell lung cancer (NSCLC). Effective treatments are limited for chemorefractory metastatic colorectal cancer (mCRC). METHODS: amplification. Participants with left-sided mCRC without (cohort A) or with (cohort B) prior anti-EGFR antibody treatment, or right-sided mCRC (cohort C) regardless of prior anti-EGFR treatment, received intravenous amivantamab 1,050 mg (1,400 mg for ≥80 kg) once every 2 weeks. The primary end point was objective response rate (ORR) per RECIST v1.1. RESULTS: By October 31, 2024, 94 participants received amivantamab monotherapy (median follow-up, 11.9 months). The median age was 60 years, and 65% of participants were male, with a median of 2 prior lines (94%, prior bevacizumab). In left-sided cohorts, the ORR was 29% (5 of 17) in cohort A and 19% (10 of 54) in cohort B; the median duration of response (DoR) was 9.0 months and 6.1 months, and the median progression-free survival (PFS) was 5.7 months and 4.6 months, respectively. In the right-sided cohort, the ORR was 22% (10 of 23; 43% had prior anti-EGFR), the median DoR was 9.8 months, and the median PFS was 3.7 months. Most frequent treatment-related grade ≥3 adverse events (AEs) were rash (7%), dermatitis acneiform (4%), and hypoalbuminemia (4%). One participant discontinued amivantamab because of a treatment-related AE. CONCLUSION: Amivantamab monotherapy demonstrated promising, durable antitumor activity in chemorefractory mCRC, regardless of prior anti-EGFR therapy and the primary tumor location. The amivantamab safety profile in mCRC is consistent with experience in NSCLC. Amivantamab plus chemotherapy is currently being explored in two phase III studies in first-line and second-line mCRCs.

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Journal
Journal of Clinical Oncology
Published
2026-04-21
DOI
https://doi.org/10.1200/jco-25-02187
Primary Topic
Colorectal Cancer Treatments and Studies
Type
article
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article

Amivantamab Monotherapy in Chemorefractory RAS / BRAF Wild-Type Metastatic Colorectal Cancer: Results From OrigAMI-1, an Open-Label, Phase Ib/II Study

J. Randolph Hecht, Víctor Moreno, Rianka Bhattacharya, Han Sang Kim et al.
Journal of Clinical Oncology
Colorectal Cancer Treatments and Studies
article

Amivantamab Monotherapy in Chemorefractory RAS / BRAF Wild-Type Metastatic Colorectal Cancer: Results From OrigAMI-1, an Open-Label, Phase Ib/II Study

J. Randolph Hecht, Víctor Moreno, Rianka Bhattacharya, Han Sang Kim, Cathy Eng, Susana Roselló‐Keränen, Yong Sang Hong, Jeeyun Lee, Myung Ah Lee, Hung‐Chih Hsu, Rozita Abdul Malik, Sabine Tejpar, Volker Heinemann, Kanwal P. S. Raghav, Meena Thayu, Chia‐Chi Lin, Ying Yuan, Robert W. Schnepp, Seung‐Hoon Beom, Dirk Arnold, Sae‐Won Han, Mahadi Baig, Hans Prenen, Patricia Lorenzini, Eric X. Chen, Emrullah Yilmaz, Ryota Iwasawa, Filippo Pietrantonio, Bharvin Patel, Eric Van Cutsem, Sanjib Chowdhury, John Xie, Joshua C. Curtin, Héctor Vélez, Xuesong Lyu, Harvey Yu-Li Su, Paul E. Oberstein, Sreenivasa Chandana, Azura Ahmad, Carlos Lopez, Marcia Cruz-Correa, Mahesh Daksh, Yu-Min Yeh, Medha Kamat, Kuan-Ming Lai
article en

Abstract

PURPOSE: Amivantamab, an EGFR-MET bispecific antibody with immune cell-directing activity, is approved in non-small cell lung cancer (NSCLC). Effective treatments are limited for chemorefractory metastatic colorectal cancer (mCRC). METHODS: amplification. Participants with left-sided mCRC without (cohort A) or with (cohort B) prior anti-EGFR antibody treatment, or right-sided mCRC (cohort C) regardless of prior anti-EGFR treatment, received intravenous amivantamab 1,050 mg (1,400 mg for ≥80 kg) once every 2 weeks. The primary end point was objective response rate (ORR) per RECIST v1.1. RESULTS: By October 31, 2024, 94 participants received amivantamab monotherapy (median follow-up, 11.9 months). The median age was 60 years, and 65% of participants were male, with a median of 2 prior lines (94%, prior bevacizumab). In left-sided cohorts, the ORR was 29% (5 of 17) in cohort A and 19% (10 of 54) in cohort B; the median duration of response (DoR) was 9.0 months and 6.1 months, and the median progression-free survival (PFS) was 5.7 months and 4.6 months, respectively. In the right-sided cohort, the ORR was 22% (10 of 23; 43% had prior anti-EGFR), the median DoR was 9.8 months, and the median PFS was 3.7 months. Most frequent treatment-related grade ≥3 adverse events (AEs) were rash (7%), dermatitis acneiform (4%), and hypoalbuminemia (4%). One participant discontinued amivantamab because of a treatment-related AE. CONCLUSION: Amivantamab monotherapy demonstrated promising, durable antitumor activity in chemorefractory mCRC, regardless of prior anti-EGFR therapy and the primary tumor location. The amivantamab safety profile in mCRC is consistent with experience in NSCLC. Amivantamab plus chemotherapy is currently being explored in two phase III studies in first-line and second-line mCRCs.

Journal of Clinical Oncology
University Health Network (CA), Johnson & Johnson (United States) (US), The University of Texas MD Anderson Cancer Center (US), University of Puerto Rico, Medical Sciences Campus (PR), Ponce Health Sciences University (PR), Yonsei University (KR), University of Puerto Rico System (PR), Vanderbilt University (US), Severance Hospital (KR), Universitair Ziekenhuis Leuven (BE), Asan Medical Center (KR), Samsung Medical Center (KR), Princess Margaret Cancer Centre (CA), Seoul National University Hospital (KR), University of Malaya (MY), Asklepios Klinik Altona (DE), NYU Langone Health (US), Kaohsiung Chang Gung Memorial Hospital (TW), Hospital Clínico Universitario de Valencia (ES), Marqués de Valdecilla University Hospital (ES), Antwerp University Hospital (BE), Instituto de Investigación Marqués de Valdecilla (ES), Linkou Chang Gung Memorial Hospital (TW), South Texas Accelerated Research Therapeutics (US), Vall d'Hebron Hospital Universitari (ES), Johnson Electric (China) (CN), Hospital Universitario Fundación Jiménez Díaz (ES), National Taiwan University Hospital (TW), Fondazione IRCCS Istituto Nazionale dei Tumori (IT), Start Treatment & Recovery Centers (US), Second Affiliated Hospital of Zhejiang University (CN), National Cheng Kung University Hospital (TW), Changhua Christian Hospital (TW), The Catholic University of Korea Seoul St. Mary's Hospital (KR), UCLA Jonsson Comprehensive Cancer Center, Vanderbilt-Ingram Cancer Center, Ludwig-Maximilians-Universität München (DE), Catholic University of Korea (KR), KU Leuven (BE)
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Colorectal Cancer Treatments and Studies
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