In a phase Ib/II study (OrigAMI-1) reported in the Journal of Clinical Oncology, Oberstein et al found that the EGFR-MET bispecific antibody amivantamab-vmjw showed activity when used as monotherapy in patients with chemorefractory RAS/BRAF wild-type metastatic colorectal cancer.
Study Details
In the international trial, 94 patients had received amivantamab monotherapy by October 2024 at 1,050 mg (1,400 mg for body weight ≥ 80 kg) once every 2 weeks. Patients had received two to three lines of prior therapy, and 94% had received prior bevacizumab. Patients were segregated into three cohorts: left-sided primary disease with (n = 17) or without (n = 54) receipt of prior anti-EGFR antibody treatment, and right-sided primary disease (n = 23) irrespective of prior anti-EGFR antibody treatment. The primary endpoint of the trial was objective response rate.
Key Findings
In the left-sided cohort with prior anti-EGFR antibody treatment, objective responses (all partial) were observed in 10 (19%, 95% confidence interval [CI] = 9%–31%) of 54 patients. Median duration of response was 6.1 months (95% CI = 1.9–8.9 months) and median progression-free survival was 4.6 months (95% CI = 3.5–5.6 months).
In the left-sided cohort with no prior anti-EGFR antibody treatment, objective responses (all partial) were observed in 5 (29%, 95% CI = 10%–56%) of 17 patients. Median duration of response was 9.0 months (95% CI = 7.3 months to not estimable) and median progression-free survival was 5.7 months (95% CI = 3.6–7.4 months).
In the right-sided cohort (43% with prior anti-EGFR antibody treatment), objective responses were observed in 10 (22%, 95% CI = 8%–44%) of 23 patients, with complete response in 1. Median duration of response was 9.8 months (95% CI = 3.7 months to not estimable) and median progression-free survival was 3.7 months (95% CI = 3.4–5.5 months).
Among all patients, the most frequent treatment-related grade ≥ 3 adverse events were rash (7%), dermatitis acneiform (4%), and hypoalbuminemia (7%). One participant discontinued amivantamab due to a treatment-related adverse event.
The investigators concluded: “Amivantamab monotherapy demonstrated promising, durable antitumor activity in chemorefractory metastatic colorectal cancer, regardless of prior anti-EGFR therapy and the primary tumor location. The amivantamab safety profile in metastatic colorectal cancer is consistent with experience in [non–small cell lung cancer]. Amivantamab plus chemotherapy is currently being explored in two phase III studies in first-line and second-line metastatic colorectal cancers.”
Paul E. Oberstein, MD, of NYU Langone Health, New York, is the corresponding author for the Journal of Clinical Oncology article.
DISCLOSURE: The study was supported by Janssen Research & Development, LLC, a Johnson & Johnson Company. For full disclosures of the study authors, visit ascopubs.org.
