FDA grants accelerated approval to Rybrevant Faspro for head and neck squamous cell carcinoma; ORR 42 percent
The FDA granted accelerated approval to amivantamab and hyaluronidase-lpuj for adults with recurrent or metastatic head and neck squamous cell carcinoma after platinum-based chemotherapy and an anti-PD-(L)1 antibody; the overall response rate was 42 percent in 102 patients.
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The FDA said it granted accelerated approval to amivantamab and hyaluronidase-lpuj (Rybrevant Faspro, Janssen Biotech, Inc.) 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-(L)1 antibody. In the OrigAMI-4 trial, overall response rate (ORR) was 42% (95% CI: 32%, 52%) in 102 patients, with 56% of responders having a duration of response of 6 months or more. The FDA said the product is not indicated for patients with oropharyngeal squamous cell carcinoma (OPSCC) that is HPV-associated.
| Indication | Population | Disease progressed on or after | Status |
|---|---|---|---|
| NSCLC | adults with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations | platinum-based chemotherapy | Listed on the label published October 30, 2026 |
| HNSCC | adults with recurrent or metastatic HNSCC | platinum-based chemotherapy and an anti-PD-(L)1 antibody | Accelerated approval granted November 5, 2026 |
From the FDA announcement of November 5, 2026 and the DailyMed label published October 30, 2026.
Why it matters
Before this approval, the label for Rybrevant Faspro, published October 30, 2026, listed uses in NSCLC only. Those uses include a single-agent indication for adults with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations whose disease has progressed on or after platinum-based chemotherapy. The FDA said the head and neck approval is for a different group of patients: those with recurrent or metastatic HNSCC who have already received platinum-based chemotherapy and an anti-PD-(L)1 antibody. The label describes amivantamab as a bispecific EGF receptor-directed and MET receptor-directed antibody combined with hyaluronidase, for subcutaneous use only.
Approval details
The FDA granted the approval on November 5, 2026. The agency said:
- The application was granted priority review.
- Amivantamab and hyaluronidase-lpuj received breakthrough therapy designation.
- The review was conducted under Project Orbis, with the Brazilian Health Regulatory Agency (ANVISA), Health Canada (HC), Israel Ministry of Health (IMoH) and Singapore's Health Sciences Agency (HSA) as partners.
- The review used the Assessment Aid, a voluntary submission from the applicant.
- The recommended dose is based on body weight.
Efficacy results
The FDA said efficacy was evaluated in OrigAMI-4 (NCT06385080), a multicenter, open-label, multi-cohort clinical trial. The primary efficacy population included 102 patients with recurrent or metastatic HNSCC and did not include patients with HPV-associated OPSCC based on p16 testing results. Eligible patients were required to have received previous treatment with platinum-based chemotherapy and an anti-PD-(L)1 antibody.
Patients received single agent weight-based amivantamab and hyaluronidase-lpuj subcutaneously every 3 weeks at the recommended dose until disease progression or unacceptable toxicity. The major efficacy outcome measures were ORR and duration of response (DOR), determined by blinded independent central review (BICR) according to RECIST v1.1.
- ORR: 42% (95% CI: 32%, 52%).
- Responders with a DOR of 6 months or more: 56%.
Trial record
The registry record for OrigAMI-4 lists Janssen Research & Development, LLC as the sponsor and describes a Phase 1b/2, open-label, non-randomized study of amivantamab monotherapy and amivantamab in addition to other therapeutic agents in participants with head and neck squamous cell carcinoma. The record lists estimated enrollment of 287 and an overall status of recruiting.
The record's brief summary says the purpose is to determine safety and preliminary efficacy of amivantamab monotherapy, amivantamab with pembrolizumab, amivantamab with paclitaxel, and amivantamab with pembrolizumab and carboplatin in participants with recurrent/metastatic head and neck cancer. Cohort 1 is amivantamab monotherapy at 1600 milligrams (mg), or 2240 mg if body weight is 80 kilograms or more, on Cycle 1 Day 1, then 2400 mg (3360 mg at that weight) weekly for the rest of Cycle 1 and every 3 weeks from Cycle 2 onwards.
Safety information
The FDA said the prescribing information for the single agent includes warnings and precautions for:
- hypersensitivity and administration-related reactions
- interstitial lung disease (ILD)/pneumonitis
- dermatologic adverse reactions
- ocular toxicity
- embryo-fetal toxicity
What remains uncertain
The FDA said full prescribing information for Rybrevant Faspro is to be posted on Drugs@FDA, and the FDA's Accelerated Approval Program page says drug companies are still required to conduct studies to confirm the anticipated clinical benefit. The OrigAMI-4 record lists the study as recruiting, and the registry has no results section posted.
Sources
- FDA: FDA grants accelerated approval to amivantamab and hyaluronidase-lpuj for recurrent or metastatic head and neck squamous cell carcinoma (November 5, 2026)
- DailyMed: RYBREVANT FASPRO (AMIVANTAMAB AND HYALURONIDASE-LPUJ (HUMAN RECOMBINANT)) INJECTION, Janssen Biotech, Inc. (October 30, 2026)
- ClinicalTrials.gov: A Study of Amivantamab Alone or in Addition to Other Treatment Agents in Participants With Head and Neck Cancer, NCT06385080
- FDA: Accelerated Approval Program