Amivantamab with or without chemotherapy in right-sided metastatic colorectal cancer: Updated results from OrigAMI-1, an open-label, phase 1b/2 study.
Authors: Kanwal Pratap Singh Raghav, Eric Van Cutsem, Dirk Arnold, Paul Eliezer Oberstein, Myung Ah Lee, Marcia Cruz-Correa, Eric Xueyu Chen, Sae-Won Han, Rozita Abdul Malik, Cathy Eng, Victor Moreno, Sanjib Chowdhury, Ryota Iwasawa, Robert W. Schnepp, Rianka Bhattacharya, Patricia A Lorenzini, Mahadi Baig, Filippo Pietrantonio, Joel R Hecht
Journal: Journal of Clinical Oncology (2025)

197 Background: Amivantamab (ami) is an EGFR-MET bispecific antibody with immune cell-directing activity and is FDA approved in EGFR -mutated advanced non-small cell lung cancer. High MET expression is observed in ~68% of patients (pts) with metastatic colorectal cancer (mCRC). Additionally, MET amplification occurs in up to 23% of EGFR-resistant mCRC and is implicated in driving resistance to EGFR-targeting antibodies (EGFRi). Compared to left (L)-sided disease, right (R)-sided disease is less responsive to EGFRi and associated with poorer outcomes. We present longer follow-up data among pts with R-sided mCRC. Methods: OrigAMI-1 (NCT05379595) is assessing ami as monotherapy and combined with chemotherapy in mCRC. All pts were wild-type for KRAS , NRAS , BRAF , and EGFR ectodomain by central ctDNA testing, without ERBB2 / HER2 amplification. One ami monotherapy cohort (Cohort C) enrolled only pts with R-sided disease (all pts must have 2-3 prior lines; prior EGFRi allowed). The ami plus chemotherapy cohorts (Cohorts D [with FOLFOX] and E [with FOLFIRI) enrolled both L- and R-sided disease (1 prior line max; prior EGFRi use was exclusionary). Primary tumor locations of cecum, ascending colon, hepatic flexure, and transverse colon were considered R-sided. Response was assessed by the investigator per RECIST v1.1. Results: As of 26-Aug-2024, 23 pts with R-sided mCRC received ami monotherapy (median follow-up of 8.1 months [mo]). Median number of prior lines was 2, and 43% had prior EGFRi. There were 7 pts with R-sided disease who received ami plus FOLFOX or FOLFIRI (median follow-up of 6.5 mo); all 7 had received 1 prior line. Among pts receiving ami monotherapy, objective response rate (ORR) was 22% (5/23) and disease control rate (DCR) was 78% (18/23), with 1 achieving a complete response. Median duration of response (DoR) is 7.4 mo; response and treatment are ongoing for 3 of the 5 responders. In pts receiving ami plus FOLFOX or FOLFIRI, ORR was 43% (3/7) and DCR was 86% (6/7). Median DoR is 5.8 mo, with all 3 responders on treatment, of which 2 are ongoing response. Additional details are in the Table. Biomarker data will be presented at the meeting. Safety profile among R-sided disease was consistent with prior reports, with the most common ami-related grade 3+ AEs being rash and hypoalbuminemia (2 pts each). Conclusions: Ami monotherapy or combined with FOLFOX or FOLFIRI demonstrated durable antitumor activity in R-sided mCRC. Clinical trial information: NCT05379595 . Efficacy. Ami monotherapy (n=23) Ami + FOLFOX or FOLFIRI (n=7) Median follow-up, mo (range) 8.1 (0.6–17.5) 6.5 (3.2–8.8) Median number prior lines 2 1 Prior EGFRi, n (%) 10 (43) 0 ORR, % (95% CI) 22 (8–44) 43 (10–82) Median DoR, mo (95% CI) 7.4 (3.7–NE) 5.8 (NE–NE) a DCR, % (95% CI) 78 (56–93) 86 (42–100) Median progression-free survival, mo (95% CI) 3.7 (3.4–5.5) 7.4 (1.8–NE) a All 3 responders remain on treatment; 2 of 3 responders are ongoing response.