Johnson & Johnson is advancing Rybrevant (amivantamab) into phase 3 trials for metastatic colorectal cancer (mCRC) following encouraging phase 1b/2 results presented at ESMO. The OrigAMI-1 study demonstrated a 49% objective response rate (ORR) with Rybrevant plus chemotherapy in patients with RAS/BRAF wild-type mCRC who had not previously received anti-EGFR therapy. This development could offer a new treatment option for a patient population with significant unmet needs.
The phase 1b/2 OrigAMI-1 study evaluated Rybrevant in combination with chemotherapy as both a first- and second-line treatment. The median duration of response was 7.4 months, and the median progression-free survival (PFS) was 7.5 months. The disease control rate, including stabilized cancers, reached 88%. Notably, Rybrevant achieved a 53% ORR in patients with liver metastases, a common occurrence in colorectal cancer. According to Filippo Pietrantonio of Fondazione IRCCS Istituto Nazionale dei Tumori, 21% of patients became eligible for potentially curative surgery following treatment with the Rybrevant regimen.
Clinical Significance and Trial Design
The current standard treatment for this type of mCRC is Eli Lilly's Erbitux (cetuximab), an anti-EGFR antibody, combined with chemotherapy. J&J plans to initiate two phase 3 trials to compare Rybrevant against Erbitux in both first- and second-line settings. These trials aim to establish Rybrevant's efficacy and safety profile relative to the existing standard of care.
Rybrevant's Mechanism and Prior Approvals
Rybrevant, a dual EGFR and MET inhibitor, received FDA approval in 2021 for NSCLC patients with EGFR exon 20 insertion mutations. Its indications were later expanded to include combination therapy with chemotherapy for the same patient group. More recently, Rybrevant gained FDA approval for first-line use in combination with J&J's third-generation EGFR tyrosine kinase inhibitor Lazcluze (lazertinib) for a broader NSCLC population, positioning it as a potential competitor to AstraZeneca's Tagrisso (osimertinib).
Market Potential and Future Outlook
Johnson & Johnson anticipates peak sales of $5 billion annually for Rybrevant. The recent NSCLC indication is considered a crucial step towards achieving this goal, and a successful foray into colorectal cancer could further bolster its market position. According to Kiran Patel, head of clinical development, solid tumors, at J&J, Rybrevant's activity beyond lung cancer, due to its unique multi-targeted approach in inhibiting EGFR and MET, represents a potentially important step forward for patients with EGFR inhibitor-naïve metastatic colorectal cancer. Colorectal cancer is the third most common cancer globally, accounting for approximately 10% of all cancer cases and the second leading cause of cancer-related deaths.
