Promising Efficacy Seen With Amivantamab Regimen in R/R Metastatic CRC

In an interview with Targeted Oncology, Filippo Pietrantonio, MD, Fondazione IRCCS Istituto Nazionale dei Tumori, summarizes new efficacy and safety data from the phase 1b/2 OrigAMI-1 study (NCT05379595) combining amivantamab (Rybrevant) with chemotherapy for treatment of patients with RAS/BRAF wild-type, relapsed/refractory metastatic colorectal cancer. These data were recently presented at the 2026 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium.

Watch the first part of Dr Pietrantonio’s interview.

The latest results from the phase 1b/2 OrigAMI-1 study showed an overall response rate (ORR) of 51% and a median progression-free survival (PFS) of 9.2 months. The data were especially encouraging in the first-line setting, where the ORR exceeded 70%, compared with over 40% in the second-line setting.

A significant clinical milestone from the study was the secondary resection of liver metastases in 6 patients, which Dr Pietrantonio described as a direct consequence of the regimen's high activity. He noted that because these patients were censored at the time of surgery per protocol, the actual efficacy results might be even stronger than what the calculated PFS suggests. This success is biologically supported by amivantamab’s ability to inhibit MET receptors, which are often highly active in the liver microenvironment.

Safety profiles were consistent with the known effects of each individual agent, with no new safety signals or added toxicity observed.

According to Dr Pietrantonio, these findings provide a strong foundation for the ongoing phase 3 studies, OrigAMI-2 (NCT06662786) and OrigAMI-3 (NCT06750094), which seek to evaluate this combination in broader clinical settings. A notable difference for these phase 3 trials is the use of a subcutaneous formulation of amivantamab, which Dr Pietrantonio believes will offer a more convenient route of administration and lead to better patient compliance than the intravenous method used in OrigAMI-1. This evolution in delivery, combined with the agent's bispecific targeting of EGFR and MET, aims to address the unmet need for patients facing primary endocrine resistance to traditional inhibitors.

Read the full interview here.