Amivantamab Plus FOLFOX/FOLFIRI Demonstrates Strong, Durable Activity in mCRC

New longer-term results from the phase 1b/2 OrigAMI-1 (NCT05379595) study show that amivantamab-vmjw (Rybrevant; Johnson & Johnson) combined with standard chemotherapy achieved encouraging antitumor activity and durable responses in patients with RAS/BRAF wild-type metastatic colorectal cancer (mCRC).¹

Presented at the 2026 American Society of Clinical Oncology (ASCO) Gastrointestinal (GI) Cancers Symposium, the data highlight early and sustained responses, low treatment-related discontinuation rates, and notable activity in patients with liver metastases, supporting further investigation of the EGFR/MET-targeting strategy in pivotal phase 3 trials.

“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,” Filippo Pietrantonio, MD, medical oncologist, National Cancer Institute of Milan, Italy, told The American Journal of Managed Care^® (AJMC^®) in an interview.²

The study was an open-label, multicenter trial designed to evaluate the safety, tolerability, and efficacy of amivantamab with either FOLFOX or FOLFIRI chemotherapy in patients with RAS/BRAF wild-type mCRC.¹ Eligible patients were confirmed to be wild-type for KRAS, NRAS, and BRAF based on circulating tumor DNA testing and were negative for HER2/ERBB2 amplification.

Participants were either treatment naive or had received a single prior line of systemic therapy in the metastatic setting, with no prior EGFR inhibitor therapy allowed. The study included cohorts receiving intravenous amivantamab plus FOLFOX or FOLFIRI. The primary end point was safety and tolerability, while secondary end points assessed overall response rate (ORR), duration of response (DOR), clinical benefit rate, and progression-free survival (PFS). Overall survival (OS) was evaluated as an exploratory end point.

At a median follow-up of 16 (range, 1.2-29.5) months, amivantamab combined with FOLFOX (n = 20) or FOLFIRI (n = 23) achieved a confirmed ORR of 51% (95% CI, 36-67), with a median time to first response of 8.3 (range, 7.3-20.3) weeks. The median DOR was 9.3 months (95% CI, 5.8-14.7), and the median PFS was 9.2 months (95% CI, 5.4-12.9).

In the first-line subgroup, ORR was 73% (95% CI, 53-86) with median DOR not yet reached, and 4 of 11 patients proceeded to curative-intent surgery.

In the second-line subgroup (n = 32), ORR was 44% (95% CI, 26-62) with a median DOR of 7.4 months (95% CI, 5.4-14.5), and more than one-third of patients remained on therapy for more than 1 year, including 3 patients continuing beyond 2 years.

Among 30 patients with liver metastases, the ORR was 57% (95% CI, 37-75) with a median PFS of 11.3 months (95% CI, 5.9-16.4). Treatment was generally well tolerated, with only 9% of patients discontinuing due to treatment-related adverse events and no new safety signals observed.

"Treatment for metastatic colorectal cancer has remained largely unchanged for many years, underscoring the need for new strategies," said Kiran Patel, MD, vice president, global head, solid tumor clinical development and companion diagnostics, Johnson & Johnson Innovative Medicine, in a statement. "We are drawing on our scientific leadership in EGFR-driven lung cancer to evaluate the potential of amivantamab and its dual-targeting of EGFR and MET in colorectal cancer and other solid tumors driven by these pathways."

These findings support continued evaluation of this dual EGFR/MET–targeting approach in ongoing phase 3 trials, offering potential new treatment options for patients who historically have had limited durable responses with standard therapies.

References

1. Rybrevant (amivantamab-vmjw) longer-term results show promising and durable responses in difficult-to-treat colorectal cancer. News release. Johnson & Johnson. January 10, 2026. Accessed January 12, 2026. https://www.prnewswire.com/news-releases/rybrevant-amivantamab-vmjw-longer-term-results-show-promising-and-durable-responses-in-difficult-to-treat-colorectal-cancer-302656931.html

2. Steinzor P, Pietrantonio F. Amivantamab plus chemotherapy delivers durable responses in RAS/BRAF wild-type mCRC: Filippo Pietrantonio, MD. AJMC. January 9, 2026. Accessed January 12, 2026. https://www.ajmc.com/view/amivantamab-plus-chemotherapy-delivers-durable-responses-in-ras-braf-wild-type-mcrc-filippo-pietrantonio-md