Johnson & Johnson announced new data from the Phase 1b/2 OrigAMI-1 study, revealing that RYBREVANT® (amivantamab-vmjw) combined with chemotherapy (mFOLFOX6 or FOLFIRI) shows promising antitumor activity in patients with RAS/BRAF wild-type metastatic colorectal cancer (mCRC) who have not previously received anti-epidermal growth factor receptor (EGFR) therapy. The findings were presented at the European Society of Medical Oncology (ESMO) 2024 Congress.
Filippo Pietrantonio, M.D., a medical oncologist at Fondazione IRCCS Istituto Nazionale dei Tumori in Milan, Italy, highlighted the significance of the study, stating, "OrigAMI-1 is the first study to show RYBREVANT plus chemotherapy may provide clinically meaningful benefits to patients with metastatic colorectal cancer who have not received any EGFR-targeted treatments as their first or second line of therapy." He also noted that 21% of patients proceeded to curative-intent surgery, underscoring the potential of RYBREVANT in this setting.
Study Details and Results
The OrigAMI-1 study included 43 patients treated with RYBREVANT in combination with either FOLFOX (20 patients) or FOLFIRI (23 patients). The median follow-up period was 7.3 months. Patients were either in their first (26%) or second line (74%) of treatment for mCRC and had not been treated with specific anti-EGFR therapies. Response was assessed per RECIST v1.1.
The combination of RYBREVANT plus chemotherapy achieved an overall response rate (ORR) of 49% (95% CI, 33-65), with a median duration of response of 7.4 months (95% CI, 5.6-NE) and a median progression-free survival of 7.5 months (95% CI, 7.4-NE). Disease control was observed in 88% of patients (95% CI, 75-96). Clinically meaningful intrahepatic antitumor activity was observed among patients with liver metastases, demonstrating a significant reduction in liver tumors (ORR of 53%, disease control rate of 93%).
Safety Profile
The safety profile of RYBREVANT plus FOLFOX/FOLFIRI was manageable and consistent with each of the individual components, without any additive toxicity. The most frequent treatment-emergent adverse events were neutropenia, rash, stomatitis, infusion-related reactions, and diarrhea. All infusion-related reactions were Grade 1 or 2, and there were no Grade 3 or higher events reported. Treatment-related discontinuations of RYBREVANT were 10% for the FOLFOX combination and 9% for the FOLFIRI combination.
Implications for Colorectal Cancer Treatment
Kiran Patel, M.D., Vice President, Clinical Development, Solid Tumors, Johnson & Johnson Innovative Medicine, emphasized the potential of RYBREVANT beyond lung cancer, stating, "Confirmation that RYBREVANT has activity beyond lung cancer, given its unique multi-targeted approach in inhibiting EGFR and MET, is a potentially important step forward for patients with EGFR inhibitor-naïve metastatic colorectal cancer." He also noted the global burden of colorectal cancer, which represents about 10% of all cancer cases and is the second leading cause of cancer-related deaths.
Pivotal Phase 3 registration trials evaluating RYBREVANT-based regimens as first- and second-line treatment in colorectal cancer are planned.
About RYBREVANT
RYBREVANT® (amivantamab-vmjw) is a fully-human bispecific antibody targeting EGFR and MET with immune cell-directing activity. It is approved in the U.S., Europe, and other markets as monotherapy for the treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations, as detected by an FDA-approved test, whose disease has progressed on or after platinum-based chemotherapy. It is also approved in combination with chemotherapy for the first-line treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations.
