Multinational phase 1b-2 study of aminvantamab in chemorefractory RAS/BRAF wild-type metastatic colorectal cancer

Amivantamab, an EGFR-MET bispecific antibody with immune cell-directing activity, is approved in non-small cell lung cancer. The multinational phase 1b-2 study OrigAMI-1 study evaluated amivantamab for chemorefractory metastatic colorectal cancer (mCRC), a malignancy with few effective treatments. The study included 94 patients with 2 or 3 prior treatment lines for RAS/BRAF/EGFR ectodomain wild-type status mCRC, without ERBB2 amplification. Participants with left-sided mCRC without (cohort A) or with (cohort B) prior anti-EGFR antibody treatment, or right-sided mCRC regardless of prior anti-EGFR treatment (cohort C) received intravenous amivantamab 1,050 mg (1,400 mg for ≥ 80 kg) once every 2 weeks. The primary endpoint was objective response rate (ORR). The median follow-up for 94 participants was 11.9 months. The figure shows the antitumor activity of amivantamab. The ORR was 29% in cohort A and 19% in cohort B with median duration of response 9.0 months and 6.1 months, respectively, and median progression-free survival 5.7 months and 4.6 months. In cohort C, the ORR was 22% (43% had prior anti-EGFR), the median duration of response was 9.8 months, and the median progression-free survival was 3.7 months. Most frequent treatment-related grade ≥3 adverse events were rash (7%), dermatitis acneiform (4%), and hypoalbuminemia (4%). One participant discontinued amivantamab because of a treatment-related adverse event. The authors conclude that aminvantamab monotherapy demonstrated promising, durable antitumor activity in chemorefractory mCRC, regardless of prior anti-EGFR therapy and primary tumor location.