RYBREVANT FASPRO™ Shines in First-Line HNSCC with 56% Response Rate

Johnson & Johnson announced positive Phase 1b/2 OrigAMI-4 study data showing subcutaneous amivantamab combined with a PD-1 inhibitor, like pembrolizumab, achieves strong antitumor activity in first-line recurrent or metastatic PD-L1-positive, HPV-unrelated head and neck squamous cell carcinoma (HNSCC).

These findings, presented at the 2026 Multidisciplinary Head and Neck Cancers Symposium, highlight a potential advance over standard PD-1 monotherapy, which typically yields only 18% response rates.

Joshua Bauml, M.D., Vice President, Lung and Head and Neck Cancer Disease Area Leader, Johnson & Johnson said Current first-line care for recurrent/metastatic head and neck cancer yields low responses and short benefits; amivantamab’s EGFR/MET mechanism, proven in lung cancer, now shows superior rapid/durable control, addressing high unmet need.

Study Design and Patient Population

The OrigAMI-4 trial (NCT06385080) is an open-label Phase 1b/2 study evaluating RYBREVANT FASPRO™ (magatama and hyaluronidase-lpuj) across five cohorts in recurrent or metastatic HNSCC. Cohort 2 focused on first-line treatment in PD-L1-positive, HPV-unrelated patients, using weekly dosing initially then every three weeks. This bispecific antibody targets EGFR and MET pathways, key drivers of tumor growth and resistance, building on its success in EGFR-mutated non-small cell lung cancer.

Key Efficacy Outcomes

Treatment delivered a confirmed overall response rate (ORR) of 56% (22/39 patients; 95% CI, 40-72), including 10% complete responses and 18 partial responses. Tumor shrinkage occurred in 82% of patients, with a clinical benefit rate of 74% and median time to response of 9.7 weeks. At 10.4 months median follow-up, median progression-free survival reached 7.7 months, and 46% of patients remained on therapy.

Safety Profile

The combination’s safety aligned with known profiles of the individual agents, with no new signals. Common adverse events (>30%) included rash (49%), paronychia (46%), hypoalbuminemia (41%), acneiform dermatitis (38%), elevated AST/ALT (38%/36%), and stomatitis (36%). Only 10% discontinued due to treatment-related events, and administration reactions were mild.

Ranee Mehra, M.D., Director of Head and Neck Medical Oncology and Professor of Medicine, Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland said “Rapid and durable disease control is a key goal in first-line head and neck cancer treatment; subcutaneous amivantamab plus immunotherapy targets tumor growth/resistance drivers for deeper responses than standards, warranting further research”.

Clinical Context and Next Steps

HNSCC, affecting mucosal linings in the oral cavity and beyond, has poor outcomes in the recurrent/metastatic setting, especially HPV-negative cases comprising 75% of patients. These results support ongoing Phase 3 OrigAMI-5 trial (NCT07276399) evaluating the regimen with carboplatin regardless of PD-L1 status.

RYBREVANT FASPRO™, FDA-approved in December 2025 across intravenous indications, offers subcutaneous convenience via Halozyme’s ENHANZE technology. RYBREVANT FASPRO™ recently also gained FDA approval for simplified monthly dosing, enhancing ease of administration in approved indications.

Reference

RYBREVANT FASPRO™ (amivantamab and hyaluronidase-lpuj) plus immunotherapy shows strong clinical benefit with 56 percent overall response rate in first-line recurrent or metastatic head and neck cancer, 19 February 2026, RYBREVANT FASPRO™ (amivantamab and hyaluronidase-lpuj) plus immunotherapy shows strong clinical benefit with 56 percent overall response rate in first-line recurrent or metastatic head and neck cancer

A Study of Amivantamab Alone or in Addition to Other Treatment Agents in Participants with Head and Neck Cancer (OrigAMI-4), ClinicalTrials.gov ID NCT06385080, https://clinicaltrials.gov/study/NCT06385080