Rybrevant Faspro won FDA approval for head and neck cancer that comes back after chemo and immunotherapy

Adults whose head and neck squamous cell carcinoma has returned or spread after platinum-based chemotherapy and immunotherapy have a new treatment option as of Nov. 5. The FDA granted accelerated approval to Rybrevant Faspro, a subcutaneous injection of amivantamab and hyaluronidase-lpuj made by Janssen Biotech. In the trial behind the decision, 42% of 102 patients saw their tumors respond.

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Accelerated approval for recurrent or metastatic disease

The approval covers adults with recurrent or metastatic head and neck squamous cell carcinoma, abbreviated HNSCC, whose disease progressed on or after platinum-based chemotherapy and immunotherapy. It excludes HPV-associated oropharyngeal squamous cell carcinoma. The agency describes the decision as the first in 10 years for patients with recurrent or metastatic HNSCC who have already received platinum-based chemotherapy, and says currently approved therapies produce an overall response rate of about 20% or less. The drug also carries a Breakthrough Therapy designation for this use.

Angelo De Claro, M.D., director of the FDA’s Oncology Center of Excellence, said in the agency’s announcement that “Today’s approval represents a meaningful step forward for patients with head and neck squamous cell carcinoma.” He added that “This therapy offers patients and their physicians a new option.”

OrigAMI-4 and the 42% response rate

The evidence comes from OrigAMI-4, an open-label, multicenter phase 1b/2 study. In its first cohort, 102 adults who had received prior immunotherapy and platinum-based chemotherapy took the drug as a single agent. Johnson & Johnson’s May 31 data release reported a 42% overall response rate by blinded independent central review, made up of 15% complete responses and 27% partial responses. The median duration of response had not been reached at a median follow-up of 11.8 months, and the FDA says 56% of responders held their response for six months or longer.

Barbara Burtness, M.D., of Yale Cancer Center, said the high response rate, including the complete responses, suggests the drug could meaningfully improve expectations for these patients.

A J&J medical-information summary of the cohort fills in the practical picture. Dosing runs every three weeks at 2400 mg, or 3360 mg for patients weighing 80 kilograms or more. Median age was 63, investigator-assessed response was 47%, median progression-free survival was 6.8 months and median overall survival was 12.5 months. Grade 3 or higher adverse events hit 60% of patients, with hypoalbuminemia (50%), rash (37%), paronychia (34%) and acneiform dermatitis (34%) the most common events of any grade. Administration-related reactions occurred in 15%, none of them grade 3 or higher. The same page states plainly that this was a single-arm trial and that results should be interpreted with caution.

The cohort’s makeup shows who the drug was tested in. Median age was 63 and 77% of patients were men. Primary tumors were in the oral cavity for 47%, the larynx for 24%, the hypopharynx for 16% and the oropharynx for 14%. Every patient had already tried at least one earlier line of therapy: 52% had one and 48% had two. Median time to first response was 6.6 weeks, 43 patients responded, 63% of those responders were still responding at the data cutoff, and 31% of the full group remained on treatment. HPV-positive oropharyngeal cancer was excluded from the trial, which matches the carve-out in the approved indication.

Warnings on the label and the confirmatory-study condition

Single-agent labeling carries warnings and precautions for hypersensitivity and administration-related reactions, interstitial lung disease and pneumonitis, dermatologic reactions, ocular toxicity and embryo-fetal harm. In the cohort, eight patients stopped treatment because of treatment-related adverse events, including one case each of interstitial lung disease and pneumonitis.

Accelerated approval rests on a surrogate endpoint, a marker expected to predict clinical benefit, according to the FDA’s accelerated approval program page. Here the marker is tumor response. Because long-term benefit has not been confirmed, the manufacturer must run confirmatory studies, and if they fail to show a real clinical benefit, the agency has procedures that can lead to withdrawal from the market.

Two features of the evidence deserve attention. First, the drug is given as an injection under the skin, with hyaluronidase-lpuj as the enzyme partner that lets a large dose be delivered that way. Second, the 42% response rate is set against a roughly 20% benchmark for existing therapies, but the trial had no comparison arm, so the gap is a cross-trial comparison rather than a head-to-head result. J&J reported no new safety signals and said most treatment-related events were grade 1 or 2, while the label still lists the lung, skin and eye warnings above.

The road to this decision was short. CURE reported on Feb. 18 that the FDA had granted Breakthrough Therapy designation to the subcutaneous formulation as a single agent for HPV-unrelated disease, based on early OrigAMI-4 data shown at the 2025 ESMO Congress. About nine months later came the approval, and the open question for patients and oncologists is whether median survival of 12.5 months in a single-arm cohort holds up once confirmatory trials report.

This article was produced with the assistance of AI and reviewed by Morning Overview editors prior to publication.

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