Amivantamab With or Without Chemotherapy for Right-Sided Metastatic Colorectal Cancer
Filippo Pietrantonio, MD, National Cancer Institute of Milan, Italy, discusses updated results from the phase 1b/2 OrigAMI-1 trial, which showed that amivantamab with or without chemotherapy had durable antitumor activity among patients with right-sided metastatic colorectal cancer.
These results were first presented at the 2025 ASCO Gastrointestinal Cancers Symposium in San Francisco, California.
Transcript:
Hi everyone, my name is Filippo Pietrantonio, I'm a GI medical oncologist at the National Cancer Institute of Milan, in Italy, and at ASCO GI 2025 the OrigAMI-1 phase 1b/2 study subgroup analysis in patients with right-sided tumors were presented.
We know that doublet chemotherapy plus an EGFR inhibitor is the recommended standard first-line treatment for patients with RAS and BRAF wild-type and left-sided metastatic colorectal cancer. However, in patients with right-sided disease there is a level restriction in the United States for the use of panitumumab or cetuximab. In Europe, the guidelines recommend the use of chemotherapy plus an EGFR inhibitor if tumor response is needed and in patients unfit for receiving triplet chemotherapy FOLFOX plus bevacizumab. However, we also know that there is a relatively small subgroup of patients with right-sided disease and potential benefit from the use of EGFR inhibitors and some molecular hyper-selection is important to identify these patients from a genomic point of view, but also the use of more potent next generation EGFR inhibitors may play an important role.
Amivantamab is an anti-MET and EGFR bi-specific monoclonal antibody, and the OrigAMI-1 phase 1b/2 study investigated the activity and safety of amivantamab, which has a trimodal mechanism of action including receptor signaling blockade and then receptor internalization and degradation and also immune cell directing activity. OrigAMI-1 had different cohorts, cohort A was patients with left-sided tumors not pretreated with EGFR inhibitors, cohort B, left-sided tumors pretreated with EGFR inhibitors, and then cohort C, right-sided tumors irrespective of prior anti-EGFR therapy. These cohorts investigated amivantamab monotherapy. In addition, cohorts D and E investigated amivantamab in combination with doublet chemotherapy, either FOLFOX or FOLFIRI in second- or first-line setting and in patients without prior anti-EGFR therapy. At the meeting, the patients with right-sided disease, in cohorts C, D, and E, were pooled together and there were 30 patients included.
In patients treated with monotherapy, the overall response rate was 22% while in patients treated with the chemotherapy combination, the response rate was increased to 43%. In addition, progression-free survival was 3.7 months in monotherapy while 7.4 months in chemotherapy combination.
There is clear evidence of activity of amivantamab alone or in combination in patients with right-sided tumors and this is important because tumor responses were seen across a variety of mutations known to confer resistance to EGFR inhibition and to the use of first-generation EGFR inhibitors. There are 2 phase 3 trials ongoing, OrigAMI-2 and OrigAMI-3. OrigAMI-2 is investigating doublet chemotherapy plus amivantamab versus chemotherapy plus cetuximab in patients with the left-sided disease and RAF and BRAF wild-type status while OrigAMI-3 is investigating in the second-line setting chemotherapy with FOLFIRI plus amivantamab versus chemotherapy with FOLFIRI plus cetuximab or bevacizumab irrespective of primary tumor location.
Overall, these preliminary data support the potential activity and promising antitumor activity of amivantamab irrespective of primary tumor location and also irrespective of the molecular profile of the primary tumor. There is a promising role for future development and in fact, the OrigAMI-2 study will use a novel and more convenient subcutaneous formulation of amivantamab instead of the intravenous formulation used in the initial studies such as OrigAMI-1.
I thank you very much for your kind attention, and I say hi from Italy. Thank you very much.
Source:
Raghav K, Van Cutsem E, Arnold D, et al. Amivantamab with or without chemotherapy in right-sided metastatic colorectal cancer: Updated results from OrigAMI-1, an open-label, phase 1b/2 study. Presented at the 2025 ASCO Gastrointestinal Cancers Symposium. January 23-25, 2025. Abstract 197