Johnson & Johnson (JNJ) released encouraging long-term results over the weekend from its Phase 1b/2 OrigAMI-1 study, and the data suggests its cancer therapy Rybrevant might have real staying power in colorectal cancer treatment.
The trial is testing Rybrevant (amivantamab-vmjw) paired with either FOLFOX or FOLFIRI chemotherapy regimens in patients with RAS/BRAF wild-type metastatic colorectal cancer. Translation: this is for a specific genetic subset of advanced colorectal cancer patients whose tumors don't have certain common mutations.
The company says the anti-tumor activity, durable responses, and low treatment discontinuation rates from this study justify pushing forward with ongoing Phase 3 trials in both first-line and second-line colorectal cancer settings. The results were presented at the 2026 American Society of Clinical Oncology Gastrointestinal Cancers Symposium.
The Numbers Tell an Interesting Story
After a median follow-up of 16 months, the combination therapy achieved a confirmed overall response rate of 51% across 43 patients treated with either amivantamab plus FOLFOX (20 patients) or FOLFIRI (23 patients). Responses showed up quickly, with a median time to first response of just 8.3 weeks, and the median duration of response lasted 9.3 months. Median progression-free survival came in at 9.2 months.
But the real standout was the first-line subgroup, where the response rate hit 73% and the median duration of response hadn't even been reached yet when researchers cut off the data. Even more promising: among the 11 first-line patients, four were able to proceed to curative intent surgery, which is ultimately what you're hoping for in cancer treatment.
The second-line setting (32 patients who had already tried other treatments) showed a 44% response rate with a median duration of 7.4 months. What's particularly notable here is the durability—more than one-third of these second-line patients stayed on therapy for over a year, and three patients have now been on amivantamab treatment for more than two years.
For the 30 patients with liver metastases, which typically represent a tougher challenge, the therapy still showed meaningful activity with a 57% response rate and median progression-free survival of 11.3 months.
The safety profile remained consistent with previous reports of amivantamab combined with chemotherapy in colorectal cancer, matching what's already known about these individual agents.