Antitumor Activity Demonstrated in Later-Line Therapy

Johnson & Johnson (JNJ)'s OrigAMI-4 is a global non-randomized, open-label Phase 1b/2 trial evaluating RYBREVANT FASPRO (amivantamab and hyaluronidase-lpuj). Cohort 1 included 102 patients with HPV-unrelated recurrent/metastatic head and neck squamous cell carcinoma who had progressed after platinum-based chemotherapy and PD-1/PD-L1 inhibitors. The blinded independent central review (BICR) objective response rate (ORR) was 42%, with a complete response rate of 15%, surpassing the ORR of 21–24% reported with paclitaxel or cetuximab in the same treatment line. Despite the limitations of a single-arm study, the results generated response signals sufficient to support regulatory discussions in a patient population with limited treatment options.

Significance of Duration and Survival Data

As of the data cutoff on March 18, 2026, the median follow-up was 11.8 months, and the median duration of response (DoR) was not reached, with 56% of responders maintaining their response for six months or longer. The median progression-free survival (PFS) was 6.8 months, and the median overall survival (OS) was 12.5 months. The treatment-related discontinuation rate was 8%, and no new safety signals were observed, suggesting both the efficacy and feasibility of the subcutaneous formulation. However, due to the absence of a control group, survival superiority must be validated in a randomized Phase 3 trial.

Expansion Strategy Targeting EGFR and MET Dual Pathways

Amivantamab is a bispecific antibody that simultaneously blocks the epidermal growth factor receptor (EGFR) and mesenchymal-epithelial transition factor (MET), while inducing immune cell-mediated antitumor activity. The biological rationale for expanding the indication is based on the observation that 80–90% of p16-negative recurrent/metastatic head and neck cancers overexpress EGFR and MET. In addition to monotherapy, OrigAMI-4 is evaluating combinations with KEYTRUDA (pembrolizumab, PD-1), paclitaxel, and KEYTRUDA plus carboplatin. The trial aims to enroll 287 patients, starting on April 22, 2024, with a primary completion date planned for December 27, 2032.

Regulatory Pathway and Competitive Landscape

The FDA granted accelerated approval to RYBREVANT (amivantamab-vmjw) for EGFR exon 20 insertion non-small cell lung cancer on May 21, 2021, and approved the subcutaneous formulation of RYBREVANT FASPRO for the existing intravenous formulation's lung cancer indication on December 17, 2025. In head and neck cancer, the FDA granted Breakthrough Therapy designation on February 18, 2026, followed by Priority Review on July 2026, which is a procedural expedited review rather than final approval. The current standard of care for recurrent/metastatic disease is KEYTRUDA (Merck & Co., MRK) as monotherapy or in combination with platinum and 5-FU, while later-line therapies include ERBITUX (cetuximab, EGFR), paclitaxel, and docetaxel. The head and neck cancer market in the top eight countries was estimated at $3.76 billion in 2024, offering J&J a significant opportunity to expand its lung cancer-focused assets into a new solid tumor revenue stream.