Johnson & Johnson disclosed that its bispecific antibody RYBREVANT (amivantamab‑vmjw) achieved a 73% overall response rate in the first‑line subgroup of the Phase 1b/2 OrigAMI‑1 study for RAS/BRAF wild‑type metastatic colorectal cancer. The responses were durable, lasting beyond 16 months, and the median duration of response has not yet been reached.
The 73% response rate represents a substantial improvement over the 49% rate reported in September 2024, underscoring the drug’s growing efficacy profile. The data suggest that RYBREVANT could become a valuable first‑line option, particularly for patients with liver metastases who historically experience poorer outcomes.
RYBREVANT’s bispecific design targets both EGFR and MET, two receptors that drive tumor growth and mediate resistance to conventional EGFR inhibitors. By simultaneously blocking both pathways, the antibody can overcome resistance mechanisms that limit the effectiveness of existing therapies, explaining the high response rate and durable benefit observed.
The company is advancing RYBREVANT through Phase 3 trials—OrigAMI‑2 and OrigAMI‑3—in first‑ and second‑line colorectal cancer settings. Positive Phase 1b/2 data support the likelihood of regulatory approval and reinforce J&J’s strategy to expand its oncology portfolio with bispecific antibodies.
Dr. Filippo Pietrantonio, an investigator in the OrigAMI‑1 study, noted that “amivantamab combined with chemotherapy delivers meaningful and durable benefit,” highlighting the clinical promise of the combination and its potential to change the treatment landscape.
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