SPOTLIGHT: Amivantamab Trial Data Promise New Hope for Colorectal Cancer Treatment

The OrigAMI-2 study (NCT06662786) was designed to compare amivantamab, a novel bispecific antibody targeting EGFR and MET receptors, with standard chemotherapy to potentially improve treatment outcomes in patients with metastatic colorectal cancer (mCRC), says Dirk Arnold, MD, PhD, medical director, Asklepios Tumor Biology Center Hamburg, who spoke with The American Journal of Managed Care (AJMC).

The study design was presented in an abstract at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting.

This transcript has been lightly edited.


AJMC: What is the rationale for selecting amivantamab over cetuximab in this first-line setting, particularly given the bispecific EGFR-MET mechanism and prior approvals in lung cancer?

Dirk Arnold, MD, PhD | Image: ESMO

Arnold: Amivantamab is an interesting drug, of course, for humans, which seems to be dependent on RAS regulation, as well as on MET and…other activities of targeted agents in combination with chemotherapy. And specifically, amivantamab in its mechanism of action, being free functional, so to say, being an anti-EGFR inhibitor, being a MET inhibitor, and next to these 2 targets, also via the FC [fragment crystallizable] region of this antibody, resulting in presenting some immune cell–directed activity, including antibody-dependent cytotoxicity. This makes this a highly interesting, attractive target for treatment of colorectal cancer, and we have seen this activity of this drug also in lung cancer, mainly adenocarcinoma of the bronchus. Therefore, it’s interesting to evaluate this in colorectal cancer. And in fact, it’s not the very first thing [that] we are doing here.

When we now think about this phase 3 trial, we’re coming from a phase 1/2 trial, which has been done in first- and second-line treatment, being a combination of this free functional antibody with doublet chemotherapy regimen in suitable patients for this treatment, and this means patients with metastatic colorectal cancer and RAS and BRAF wild-type status, because we do know that anti-EGFR treatments work best in this condition of patients. And this affects 50% of all mCRC patients, and that’s the target population.

We’ll see it’s a large number of patients. We have to improve treatment strategies for those patients, and most likely, these free functional antibodies may work better [than] the former standard of care, which is an anti-EGFR receptor antibody in combination with chemotherapy. I think it’s worth [investigating] it in this phase 3 trial, and that’s now the plan of things [that] are on the way.

Reference
Arnold D, Cervantes A, Ducreux MP, et al. OrigAMI-2: a randomized, phase 3 study of amivantamab vs cetuximab, both in combination with FOLFOX or FOLFIRI, as first-line treatment in left-sided RAS/BRAF wild-type metastatic colorectal cancer. J Clin Oncol. 2025;43(suppl 16):TPS3636. doi:10.1200/JCO.2025.43.16_suppl.TPS3636