Amivantamab Shows Potential to Unlock Curative Surgery in Metastatic CRC

In an interview with Targeted Oncology, Filippo Pietrantonio, MD, Fondazione IRCCS Istituto Nazionale dei Tumori, discusses the potential of amivantamab (Rybrevant) to redefine surgical eligibility for patients with RAS/BRAF wild-type, relapsed/refractory metastatic colorectal cancer.

Watch part 1 and part 2 of Dr Pietrantonio’s interview.

By combining this bispecific antibody with chemotherapy, investigators are seeing robust response rates that may facilitate curative-intent procedures in patients previously deemed unresectable. In updated data from the phase 1b/2 OrigAMI-1 study (NCT05379595) presented this month at the 2026 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium, 6 patients were able to undergo curative intent surgery. Ongoing phase 3 research is being designed to confirm if amivantamab delivers a greater depth of response and more rapid tumor reduction than existing first-generation EGFR inhibitors, according to Dr Pietrantonio.

The probability of a patient undergoing secondary resection—which can involve the liver, lungs, peritoneum, or lymph nodes—depends heavily on the extent and quality of the therapeutic response. Dr Pietrantonio shared a potential biological rationale for the drug's efficacy, specifically within the liver: the liver microenvironment is known for high production of HGF, the signaling ligand that activates the MET receptor. Consequently, amivantamab’s dual-targeting mechanism may be uniquely equipped to neutralize tumor activity in the liver by blocking these specific bypass signals.

Read the full interview here.