FDA Fast-Tracks a J&J Head and Neck Cancer Drug on Tumor Shrinkage, and Its Announcement Names No Confirmatory Trial

On November 5, Angelo De Claro, director of the Food and Drug Administration’s Oncology Center of Excellence, announced the agency’s first approval in a decade for patients with recurrent or metastatic head and neck cancer who have already had platinum chemotherapy. The drug is Johnson & Johnson’s Rybrevant Faspro, an injectable form of amivantamab. De Claro said it gives patients and their doctors “a new option with the potential to make a real difference in people’s lives.” The approval is accelerated, so it rests on how often tumors shrank (42 percent of patients in the trial responded) and how long they stayed shrunk, not on evidence that anyone lives longer. The FDA’s announcement says as much: it is not yet confirmed that the responses translate into clinically meaningful benefit, and the agency has required confirmatory studies to verify it. The announcement does not name those studies, the endpoint they have to meet or the date their results are due.

The label covers adults whose disease progressed on or after platinum chemotherapy and immunotherapy, excluding HPV-associated cancers of the oropharynx. The data first appeared on May 31 in an oral session at the American Society of Clinical Oncology meeting in Chicago, where Barbara Burtness, a medical oncologist at Yale Cancer Center, presented them. Patients in this situation, she said in J&J’s release, “face very poor outcomes.” A footnote to the same release discloses that she has served as a consultant to Johnson & Johnson.

One cohort, 102 patients, nobody randomized

The approval rests on the first cohort of OrigAMI-4, an open-label phase 1b/2 study that enrolled 102 patients and compared them with no one. According to Targeted Oncology’s account of the ASCO data, 52 percent had one prior line of treatment for recurrent or metastatic disease and 48 percent had two. Every patient was ECOG 0 or 1, meaning fully active or only mildly limited, which is a fitter group than many people who reach this point in the disease. The trial excluded p16-positive oropharyngeal cancers, the HPV-driven kind, as OncLive’s report also describes. J&J says about 80 percent of recurrent or metastatic cases are not driven by HPV.

Blinded central reviewers confirmed responses in 42 percent of patients, 15 percent complete and 27 percent partial. The investigators’ own count was 47 percent, and the FDA published the lower, independently reviewed figure, which is to its credit. Responses came quickly, at a median of 6.6 weeks. At a median follow-up of 11.8 months the median duration of response had not been reached, and the FDA reports that 56 percent of responders held their response for six months or longer. The agency puts currently approved therapies at a response rate “of around 20% or less.”

A response rate counts shrinking tumors. It does not count months of life, and a single-arm trial cannot supply that count at all. Median progression-free survival in OrigAMI-4 was 6.8 months and median overall survival was 12.5 months, with 54 percent of patients alive at one year. Without a control group there is no way to tell how much of that belongs to the drug and how much to the kind of patient fit enough to enroll in an early-phase trial.

The subgroup breakdown complicates the headline further. Among patients whose cancer began in the oral cavity, 27 of 48 responded, or 56 percent. Among the other 54 patients, a pooled group covering every other primary site, 16 responded, or 30 percent. Oral cavity patients therefore supplied 27 of the 43 confirmed responders. For everyone else the response rate sits closer to the FDA’s old 20 percent benchmark than to the 42 percent in the announcement, and a comparison across trials settles nothing either way. The label covers them all the same.

Ten years ago, the same bet

The last approval the FDA’s announcement is measuring against came in August 2016, when Merck’s Keytruda won accelerated approval for head and neck cancer that had progressed after platinum chemotherapy. That decision also rested on response rate, from a nonrandomized cohort of 174 patients with a 16 percent response rate. A 2018 systematic review in Clinical Otolaryngology caught the mood of the time: checkpoint inhibitor response rates “in the range of 20%,” durable responses and dozens of trials underway.

Merck then ran the randomized trial. In KEYNOTE-040, a Merck-funded phase 3 study, 495 patients were randomized to pembrolizumab or to methotrexate, docetaxel or cetuximab. Median overall survival was 8.4 months on pembrolizumab and 6.9 months on standard of care, a hazard ratio of 0.80 with a p-value the authors themselves labeled nominal. The drug helped, by a month and a half between the two medians. That modest gap is what remained once a randomized comparison replaced the optimism that response rates had invited.

OrigAMI-4’s 12.5-month median survival looks better than KEYNOTE-040’s 8.4 months. That is not a comparison either: the trials ran years apart, in patients with different prior treatments, and no one has randomized anyone against amivantamab in this setting.

The trial the announcement leaves out

The regulatory path was quick. The drug carried Breakthrough Therapy designation in this disease, and BioPharm International reported its priority review on July 30, noting that the subcutaneous product had won its first approval, in EGFR-mutated lung cancer, in December 2025. The head and neck approval followed about three months later.

The only phase 3 head and neck trial named in J&J’s ASCO release is OrigAMI-5 (NCT07276399), which tests amivantamab with carboplatin and pembrolizumab as a first-line treatment. That is a combination, given earlier in the disease, to patients who have not yet had the platinum and immunotherapy this label requires. Whether the FDA counts it toward the confirmatory obligation for a later-line, single-drug approval, nothing public says.

A competitor is taking the harder route. Merus is running LiGeR-HN2, a randomized phase 3 trial of its EGFR-targeting bispecific antibody petosemtamab in patients whose disease progressed after anti-PD-1 and platinum therapy, against investigator’s choice of single-agent treatment, with overall survival among its primary endpoints. At ASCO, J&J’s Yusri Elsayed said that “subcutaneous amivantamab is the only therapy of its kind being studied in this disease.” The qualifiers do a lot of work in that sentence. J&J reached the market with a single arm. Merus is still trying to show survival against a control.

The side effects are the ones an EGFR-blocking drug brings, and they are common. Half the patients developed hypoalbuminemia, a drop in blood protein. Rash affected 37 percent, and paronychia (painful inflammation around the nails) and acneiform dermatitis each affected 34 percent. Fifteen percent had administration-related reactions, all low grade, and 8 percent stopped treatment because of treatment-related side effects. One patient died of treatment-related pneumonitis; investigators judged five other deaths from adverse events unrelated to the drug. The FDA’s warnings cover hypersensitivity reactions, lung inflammation, skin and eye toxicity and harm to a fetus.

For someone whose cancer has already progressed through chemotherapy and immunotherapy, those trade-offs may be worth taking, and 15 of the 102 patients had complete responses. The drug shrank tumors. The trial was not built to show whether it lengthens lives. The last time the FDA opened this door for these patients, in 2016, it took a randomized trial to learn what a response rate was worth in months. This time the agency’s announcement tells patients that a confirmatory study is required and leaves out its name, its endpoint and its deadline.

Sources

1. FDA: FDA Grants Accelerated Approval to a New Treatment for Head and Neck Squamous Cell Carcinoma
2. Johnson & Johnson: OrigAMI-4 pivotal data press release, ASCO 2026
3. Targeted Oncology: SC amivantamab achieves strong response rate in HNSCC
4. The Lancet: Cohen et al., KEYNOTE-040, pembrolizumab versus methotrexate, docetaxel, or cetuximab
5. ClinicalTrials.gov: LiGeR-HN2, petosemtamab versus investigator’s choice monotherapy (NCT06496178)
6. OncLive: Amivantamab in recurrent/metastatic HNSCC after immune checkpoint inhibitor and chemotherapy
7. BioPharm International: Rybrevant Faspro receives FDA priority review in head and neck cancer
8. Merck: FDA approves Keytruda for recurrent or metastatic HNSCC after platinum chemotherapy
9. Clinical Otolaryngology: Dogan et al., Current studies of immunotherapy in head and neck cancer