Amivantamab Plus Chemotherapy Improves Outcomes in RAS/BRAF Wild-Type Melanoma
At this year’s American Society of Clinical Oncology (ASCO) Gastrointestinal (GI) Cancers Symposium, Filippo Pietrantonio, MD, medical oncologist, National Cancer Institute of Milan, Italy, shares new data from the OrigAMI-1 (NCT05379595).
With durable responses, encouraging survival outcomes, and evidence that some patients may become eligible for curative-intent surgery, the combination of amivantamab with standard chemotherapy could signal a meaningful shift in how this molecularly defined population is treated.
This transcript was lightly edited for clarity.
The American Journal of Managed Care® (AJMC®): Can you provide a brief background of the study?
Pietrantonio: OrigAMI-1 is a phase 1/2 study investigating the role of the bispecific EGFR-MET [mesenchymal-epithelial transition] monoclonal antibody amivantamab in patients with wild-type colorectal cancer. This study was a proof-of-concept, signal-seeking trial investigating amivantamab, a next-generation EGFR inhibitor with a trimodal mechanism of action. The agent works through EGFR receptor blockade, receptor internalization and degradation, and cell-directing activity.
The study was a multicohort study, including 3 monotherapy cohorts: left-sided EGFR-refractory patients, left-sided EGFR-experienced patients, and right-sided patients previously exposed to EGFR inhibitors.
In this poster at ASCO GI 2026,data from the 2 chemotherapy combination cohorts were presented. In these cohorts, patients with no more than 1 prior line of therapy and who were EGFR-naive were treated with either FOLFIRI [leucovorin (folinic acid), fluorouracil, and irinotecan] plus amivantamab or FOLFOX [folinic acid, fluorouracil, and oxaliplatin] plus amivantamab. Updated results were presented hear.
AJMC: With an overall response rate (ORR) of 51% and some patients on treatment for more than 1 year, how do you interpret the clinical impact of these longer follow-up results for amivantamab plus chemotherapy?
Pietrantonio: This is realy promising, because I remember when I presented the initial results of these 2 chemotherapy combination cohorts, which was at ESMO [European Society for Medical Oncology] 2023, with updated results and a median follow-up of 16 months, the outcomes had improved compared with the presentation 2 years ago. basically, the response rate is slightly improved with additional follow-up, and a 51% overall response rate in patients treated mostly in the second-line setting is really promising considering historical data with first-generation EGFR inhibitors in combination with doublet chemotherapy.
These results compare favorably because progression-free survival of 9.2 months is definitely worth further investigation.This is also the reason why there are 3 ongoing studies to confirm these positive results, because OrigAMI-1 is, of course, a nonrandomized clinical trial, so randomized, prospective confirmation is needed.
AJMC: Responses were higher in the first-line subgroup. How might this influence where amivantamab fits in the mCRC treatment sequence?
Pietrantonio: Absolutely. The results were, of course, translated in the first-line set, representing a small cohort, so we cannot draw negative conclusions, but the results in terms of response rate and progression-free survival were definitely in the first line. This is expected because,of course,these patients are both chemotherapy and EGFR naive,and using ami
Key Takeaways from the Interview with Dr. Pietrantonio on Amivantamab in Colorectal Cancer:
Here’s a breakdown of the key points from the interview, organized for clarity:
1. Amivantamab’s Potential Role in Treatment:
* Current Use: Currently used in combination with doublet chemotherapy and a first-generation EGFR inhibitor for patients with EGFR-mutated metastatic colorectal cancer.
* Future Potential: Amivantamab may replace first-generation EGFR inhibitors. It could also be used with EGFR inhibition in the first-line setting for challenging populations like those with:
* Right-sided tumors
* Alterations causing primary resistance to first-generation EGFR inhibitors.
2. Curative Surgery & Liver Metastasis:
* Secondary Resection: 6 patients achieved secondary resection of metastasis, indicating critically important response to amivantamab.
* Liver Metastasis Response: Patients with liver metastasis showed slightly superior response and progression-free survival. This suggests HGF (hepatocyte growth factor) may play a role in amivantamab’s efficacy in the liver microenvironment due to the dual blockade of EGFR and MET.
* Future Research: Further investigation is needed to explore amivantamab’s role in patients with liver metastasis, as its a common and poor-prognostic feature of colorectal cancer.
* Study Design Note: Patients undergoing resection were censored in the progression-free survival analysis, potentially underestimating the true benefit of amivantamab. Including these patients in the PFS calculation would likely show even better results.
* Conversion Therapy: Amivantamab shows promise as a conversion therapy for patients with initially unresectable liver metastasis, potentially making them eligible for radical surgery.
3. Safety & Governance:
* Manageable Safety profile: Amivantamab’s safety profile is consistent with other monoclonal antibodies.
* Subcutaneous Administration: Switching to subcutaneous administration (being investigated in Phase 3 trials) is expected to reduce infusion-related reactions and improve tolerability and compliance.
* Combination with Chemotherapy: Combining amivantamab with doublet chemotherapy (FOLFOX or FOLFIRI) did not increase toxicity. Adverse events were attributed to amivantamab (skin rash) or chemotherapy.
* Ongoing Trials: The manageable safety profile is why the combination is being investigated in phase 3 trials (OrigAMI-2 in 1st line, OrigAMI-1 in 2nd line).
In essence, Dr. Pietrantonio highlights amivantamab as a promising treatment option, especially for patients with challenging colorectal cancer profiles and those with liver metastasis, with a manageable safety profile and potential for curative surgical options.The ongoing Phase 3 trials will be crucial in defining its role in the treatment landscape.