Amivantamab Plus Chemotherapy Shows Promising Long-Term Responses in Colorectal Cancer

Longer-term follow-up from the Phase 1b/2 OrigAMI-1 study shows that amivantamab (Rybrevant) plus FOLFOX or FOLFIRI achieved a 51% overall response rate in RAS/BRAF wild-type metastatic colorectal cancer, rising to 73% in first-line patients. Responses were durable, with median progression-free survival of 9.2 months and notable activity in liver metastases, supporting ongoing Phase 3 evaluation.

Johnson & Johnson presented the updated results during a poster session at the 2026 ASCO Gastrointestinal Cancers Symposium, highlighting sustained responses with amivantamab (Rybrevant) in combination with standard chemotherapy regimens FOLFOX or FOLFIRI in patients with RAS and BRAF wild-type metastatic colorectal cancer.

"These results show the potential of amivantamab combined with chemotherapy to deliver meaningful and durable benefit for people with advanced colorectal cancer, including for those with liver metastases who have historically faced poorer outcomes. Seeing patients maintain responses for extended periods, some beyond two years, is a powerful sign of progress," said Dr. Filippo Pietrantonio, Head of the Gastrointestinal Oncology Unit, IRCCS Foundation, National Cancer Institute, Milan.

OrigAMI-1 evaluated intravenous amivantamab as monotherapy or in combination with FOLFOX or FOLFIRI in patients confirmed to be negative for KRAS, NRAS, BRAF, and EGFR mutations and without HER2 amplification. Prior EGFR inhibitor therapy was not permitted. The primary endpoint was safety, with secondary endpoints including overall response rate, duration of response, clinical benefit rate, and progression-free survival.

Across patients treated with amivantamab plus chemotherapy, the confirmed overall response rate was 51 percent. In the first-line subgroup, response rates reached 73 percent, with median duration of response not yet reached at data cutoff. Notably, four of 11 first-line patients were able to proceed to curative-intent surgery. In the second-line setting, the overall response rate was 44 percent, with more than one-third of patients remaining on therapy for over one year and three patients continuing treatment beyond two years.

Encouraging activity was also observed in patients with liver metastases, a subgroup typically associated with poorer outcomes. In this population, the overall response rate was 57 percent, and median progression-free survival extended to 11.3 months.

The safety profile of amivantamab plus chemotherapy remained consistent with prior reports and with the known toxicities of EGFR and MET inhibition and chemotherapy. Treatment discontinuation due to adverse events occurred in 9 percent of patients, with neutropenia representing the most common Grade 3 or higher event. No new safety signals were identified.

“Treatment for metastatic colorectal cancer has remained largely unchanged for many years, underscoring the need for new strategies. 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,” said Kiran Patel, M.D., VP., Global Head, Solid Tumor Clinical Development, Johnson & Johnson Innovative Medicine.

Colorectal cancer remains the third most commonly diagnosed malignancy worldwide and a leading cause of cancer-related mortality. More than half of patients eventually develop metastatic disease, with liver metastases present in approximately 70 percent of cases. In RAS/BRAF wild-type disease, resistance to first-line therapies often develops rapidly, limiting long-term benefit. In the second-line setting, historical response rates with EGFR inhibitors plus chemotherapy range from 32 to 36 percent, with median progression-free survival of 5.4 to 6.4 months. Increasing evidence points to MET alterations as a frequent driver of resistance to EGFR inhibition, supporting the rationale for dual EGFR and MET targeting.