Why Amivantamab's Approval Matters to Formulators

On November 5, 2026, the FDA granted accelerated approval to Rybrevant Faspro (amivantamab and hyaluronidase-lpuj) subcutaneous injection as a single agent for adults with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) whose disease has progressed on or after platinum-based chemotherapy and an anti–PD-L1 antibody.1 The indication excludes oropharyngeal tumors that are human papillomavirus (HPV)-associated.

The decision follows Breakthrough Therapy designation in February 2026 and Priority Review in July 2026.1 It is the first approval of a dual-targeted therapy in this setting and the first advance in second-line recurrent or metastatic HNSCC in a decade.

What Data Supported the Accelerated Approval?

The approval rests on Cohort 1 of the Phase 1b/2 OrigAMI-4 trial. The cohort enrolled 102 adults previously treated with platinum chemotherapy and anti–PD-L1 therapy, excluding those with HPV-associated oropharyngeal disease.2 Confirmed overall response rate by blinded independent central review was 42% (95% confidence interval, 32%-52%), including complete responses in 15% of patients and partial responses in 28%. Among responders, 56% maintained a response beyond 6 months.

Continued approval may be contingent on verification of clinical benefit in the Phase 3 OrigAMI-5 study, which is evaluating subcutaneous amivantamab with carboplatin and pembrolizumab as first-line treatment.1

The most common adverse reactions were rash (79%), fatigue (39%), nail toxicity (35%), stomatitis (32%), and edema (28%). Serious adverse reactions occurred in 39% of patients, and fatal adverse reactions in 6%.1

“Outcomes remain poor for patients whose head and neck cancer progresses, and treatment options are limited,” said Barbara Burtness, MD, professor of medicine, Yale Cancer Center, who has served as a consultant to Johnson & Johnson, said in a press release.1 “The OrigAMI-4 findings represent important progress and highlight the potential of dual EGFR- and MET-targeting with amivantamab as a distinct treatment approach in recurrent or metastatic head and neck cancer, excluding HPV-associated oropharyngeal squamous cell carcinoma. The meaningful responses observed in this study are encouraging for patients who have long faced limited treatment options.”

Why Does This Approval Matter?

Amivantamab is a fully human bispecific antibody targeting the epidermal growth factor receptor (EGFR) and mesenchymal-epithelial transition (MET) pathways.1 These pathways are overexpressed in 80% to 90% of recurrent and metastatic HNSCC tumors. The subcutaneous product is coformulated with Halozyme’s recombinant human hyaluronidase PH20 and given as a 5-minute injection.

The approval adds to evidence that intravenous (IV)-to-subcutaneous conversion has become a routine lifecycle strategy.3 Regulators have increasingly handled such conversions through supplemental applications, some of which earned priority review.

“The pathway to convert from IV to sub q [subcutaneous] is actually very streamlined,” said Charles Theuer, MD, PhD, chief medical officer, Halozyme.3

Enzyme-enabled delivery is also driving licensing activity. Novartis’s agreement with Alteogen, worth up to $3.2 billion, was the fourth deal of 2026 involving the same hyaluronidase platform.4

Bispecifics already carry chain-pairing and purification complexity, and coformulation with an enzyme adds stability and compatibility considerations.1 Extending one subcutaneous presentation across lung and head and neck indications may also change demand planning for drug substance and fill-finish capacity.

“For years, treatment advances in recurrent or metastatic head and neck cancer have been limited by approaches that do not fully address the underlying biology of the disease,” said Yusri Elsayed, MD, PhD, Global Therapeutic Head, Oncology, Johnson & Johnson Innovative Medicine, in a press release.1 “Rybrevant Faspro delivers a differentiated approach, targeting both EGFR and MET to address the biology that drives this disease. Having redefined outcomes in EGFR+ non–small cell lung cancer, we are unlocking the next chapter of this treatment and bringing meaningful innovation to patients with certain head and neck cancers.”

References

1. Johnson & Johnson. Johnson & Johnson announces U.S. FDA approval of RYBREVANT FASPRO (amivantamab and hyaluronidase-lpuj) as first and only dual-targeted therapy for advanced head and neck cancer. News release. November 5, 2026. Accessed November 6, 2026. View source

2. Burtness B, Rosenberg AJ, Calderon B, et al. Amivantamab in recurrent/metastatic head and neck squamous cell cancer after checkpoint inhibitor and chemotherapy: pivotal results from the phase Ib/II OrigAMI-4 study. J Clin Oncol. 2026;44(24):2271-2277. doi:10.1200/JCO-26-01042 View source

3. Mirasol F. The shift from intravenous to subcutaneous biologics in 2026. Pharmaceutical Technology. September 15, 2026. Accessed November 6, 2026. View source

4. Zubulake Z. What Novartis’s $3.2 billion enzyme licensing deal means for formulation. Pharmaceutical Technology. September 2, 2026. Accessed November 6, 2026. View source