CHICAGO, Illinois, May 31, 2026
Johnson & Johnson has reported pivotal results from the Phase 1b/2 OrigAMI-4 study, demonstrating that RYBREVANT FASPRO™ (amivantamab and hyaluronidase-lpuj) achieved strong and durable responses in patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) who had previously received immunotherapy and platinum-based chemotherapy. Presented during an oral session at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting and simultaneously published in the Journal of Clinical Oncology, the findings highlight the potential of the company’s novel EGFR- and MET-targeting bispecific therapy to address a significant unmet need in a patient population with limited treatment options and poor long-term outcomes. Johnson & Johnson has also submitted a supplemental Biologics License Application (sBLA) to the U.S. FDA seeking approval for this indication following the therapy’s Breakthrough Therapy Designation.
OrigAMI-4 Study Demonstrates Durable and Deep Clinical Responses
The pivotal OrigAMI-4 trial evaluated RYBREVANT FASPRO™ monotherapy in 102 patients with recurrent or metastatic HNSCC whose disease had progressed after both immune checkpoint inhibitor treatment and platinum-based chemotherapy. Results demonstrated a 42% confirmed overall response rate (ORR), substantially exceeding response rates typically observed with currently available therapies in this setting. Notably, more than one-third of responders achieved complete responses, representing a particularly encouraging outcome in a disease known for aggressive progression and poor survival rates.
Investigators reported a 15% complete response rate and a 27% partial response rate, while the overall clinical benefit rate reached 63%. Importantly, the median duration of response had not yet been reached after a median follow-up period of 11.8 months, indicating sustained anti-tumor activity among responding patients. Median progression-free survival reached 6.8 months, while median overall survival was 12.5 months, reinforcing the potential clinical value of the therapy for patients with few remaining treatment alternatives. These results are particularly meaningful given that recurrent and metastatic HNSCC patients often experience limited benefits from currently approved therapies after disease progression.
Dual EGFR and MET Targeting Offers Novel Treatment Approach
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RYBREVANT FASPRO™ is the first and only subcutaneous dual-targeting bispecific antibody being evaluated in recurrent and metastatic head and neck cancer. The therapy simultaneously targets epidermal growth factor receptor (EGFR) and mesenchymal-epithelial transition factor (MET), two critical pathways involved in tumor growth, disease progression, and treatment resistance. By inhibiting both signaling pathways while also engaging the immune system, the therapy is designed to provide a more comprehensive anti-cancer approach than traditional single-target treatments.
Researchers believe this dual-targeting strategy may help overcome resistance mechanisms that frequently emerge in advanced cancers. The promising efficacy observed in OrigAMI-4 supports the growing clinical relevance of bispecific antibody therapies in oncology and highlights the potential for innovative biologics to improve outcomes across multiple solid tumor types. Johnson & Johnson noted that ongoing investigations are also evaluating amivantamab-based therapies in lung cancer, colorectal cancer, and additional oncology indications.
Favorable Safety Profile Supports Regulatory Advancement
The safety findings reported in OrigAMI-4 were consistent with the established profile of amivantamab-based therapies and revealed no new safety signals. Most treatment-related adverse events were Grade 1 or Grade 2, including manageable effects associated with EGFR and MET inhibition such as rash, paronychia, dermatitis acneiform, and hypoalbuminemia. Administration-related reactions occurred in only 15% of patients, with no Grade 3 or higher events reported. Treatment discontinuation due to adverse events remained low at 8%, supporting the therapy’s overall tolerability.
The positive clinical results have already supported regulatory advancement, with Johnson & Johnson submitting an sBLA to the FDA seeking approval of RYBREVANT FASPRO™ for recurrent and metastatic HNSCC. In parallel, the ongoing Phase 3 OrigAMI-5 trial is evaluating the therapy in combination with carboplatin and pembrolizumab as a first-line treatment strategy. As head and neck cancer remains one of the most difficult-to-treat solid tumors worldwide, the OrigAMI-4 findings represent a significant milestone that could expand treatment options and improve outcomes for patients facing advanced disease after standard therapies have failed.
Source: Johnson & Johnson press release
