Longer-term follow-up from the OrigAMI clinical programs shows that RYBREVANT® (amivantamab-vmjw) plus chemotherapy delivered durable responses in patients with advanced or metastatic colorectal cancer, including sustained benefit in a first-line subgroup and a manageable safety profile.
Written By: Pharmacally Medical News Desk
Johnson & Johnson has reported longer-term results showing that RYBREVANT® (amivantamab-vmjw), when combined with standard chemotherapy, demonstrated promising and durable clinical activity in patients with advanced or metastatic colorectal cancer (mCRC), a population with limited treatment options. The data were shared from ongoing OrigAMI clinical programs evaluating amivantamab-based regimens.
Key topline results
With extended follow-up of approximately 16 months, treatment with amivantamab plus FOLFOX or FOLFIRI chemotherapy resulted in a confirmed overall response rate (ORR) of 51% across evaluable patients building on the prior interim ORR of 49% at 7.3 months median follow-up. Median DOR improved to 9.3 months from 7.4 months in earlier data, with median PFS of 7.5 months previously reported (updated PFS pending full 2026 disclosure). In a small first-line subgroup, the confirmed response rate reached approximately 73%, with many responses continuing beyond 16 months.
About the investigational regimen
RYBREVANT® (amivantamab-vmjw) is a bispecific antibody targeting both EGFR and MET, two key signalling pathways involved in colorectal cancer growth and resistance to therapy. By simultaneously blocking EGFR- and MET-driven signalling and engaging immune-mediated mechanisms, amivantamab is designed to overcome resistance seen with single-pathway inhibition.
In the OrigAMI studies (NCT05379595), amivantamab is being evaluated both as monotherapy and in combination with established chemotherapy backbones, including mFOLFOX6 and FOLFIRI, across different lines of treatment.
Dr. Filippo Pietrantonio, MD, Head of the Gastrointestinal Oncology Unit at the IRCCS Foundation, National Cancer Institute, Milan, Italy, highlighted that combining amivantamab with chemotherapy has shown the potential to deliver meaningful and durable clinical benefit in advanced colorectal cancer, including in patients with liver metastases who typically have poorer outcomes. He noted that sustained responses lasting beyond two years in some patients represent meaningful progress in a disease where long-term efficacy has historically been difficult to achieve.
Safety and tolerability
The safety profile of amivantamab in combination with chemotherapy was reported to be consistent with prior clinical experience. The most commonly observed higher-grade treatment-emergent adverse events included rash and hypoalbuminemia, along with expected chemotherapy-related toxicities. Overall, the regimen was considered manageable, with no new safety signals reported in the longer-term follow-up.
Ongoing and future development
The OrigAMI clinical program continues to evaluate amivantamab-based combinations in colorectal cancer, including later-phase randomized studies designed to confirm clinical benefit and further define the patient populations most likely to respond.
Based on the company’s press release, longer-term follow-up from the OrigAMI studies suggests that RYBREVANT® (amivantamab-vmjw) plus chemotherapy may offer durable and clinically meaningful responses in selected patients with advanced colorectal cancer. Johnson & Johnson noted that these findings support continued clinical development of amivantamab in colorectal cancer and reinforce the rationale for dual targeting of EGFR and MET, drawing on the company’s prior scientific leadership in EGFR-driven lung cancer. Confirmation from larger randomized trials will be essential to define its future role in standard clinical practice.
Disease background
Colorectal cancer remains one of the leading causes of cancer-related mortality worldwide. While advances in chemotherapy and targeted therapies have improved outcomes, patients with metastatic disease, particularly those with liver involvement or resistance to anti-EGFR therapies, continue to face limited options. Novel biologic approaches with durable responses are therefore a critical unmet need.
References
RYBREVANT® (amivantamab-vmjw) longer-term results show promising and durable responses in difficult-to-treat colorectal cancer, 10 January 2026, https://www.jnj.com/media-center/press-releases/rybrevant-amivantamab-vmjw-longer-term-results-show-promising-and-durable-responses-in-difficult-to-treat-colorectal-cancer
A Study of Amivantamab Monotherapy and in Addition to Standard-of-Care Chemotherapy in Participants with Advanced or Metastatic Colorectal Cancer (OrigAMI-1), ClinicalTrials.gov ID NCT05379595, https://clinicaltrials.gov/study/NCT05379595