Amivantamab Trial Promises New Hope for Colorectal Cancer Treatment: Dirk Arnold, MD, PhD

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 Tumour Biology Centre.

The study was presented at the American Society of Clinical Oncology (ASCO) meeting.

This transcript was lightly edited; captions were auto-generated.

Transcript

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?

Amivantamab is an interesting drug, of course, for humans, which seem to be dependent from RAS regulation, as well as from MET and from 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 interestingly attractive target for treatment of colorectal cancer, and we have seen this activity of this drug also in lung cancer, so mainly adenocarcinoma of the of the bronchus. Therefore, it's interesting to evaluate this in colorectal cancer. And in fact, it's not the very first thing which 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 compared to the former standard of care, which is an anti-EGFR receptor antibody in combination with chemotherapy. I think it's worth to investigate it in this phase 3 trial, and that's now the plan of things which are on the way.