First New Drug in Head and Neck Cancer in 10 Years: Subcutaneous Amivantamab Receives Accelerated FDA Approval
In this article
An Antibody That Targets EGFR and MET Together: A New Option for Head and Neck Cancer After Platinum and Immunotherapy
On November 5, 2026, the US Food and Drug Administration (FDA) granted accelerated approval to subcutaneous amivantamab (Rybrevant Faspro) for recurrent or metastatic head and neck squamous cell carcinoma. The approval covers adults whose disease progressed during or after platinum-based chemotherapy and immunotherapy; HPV-associated oropharyngeal cancer is not included. In the 102-patient OrigAMI-4 trial, the tumor shrank markedly or disappeared in 42% of patients. According to the FDA, this is the first new drug approval in 10 years for this group of patients previously treated with platinum. In this article, we explain how the drug works, the strengths and limits of the evidence, its side effects and the situation in Türkiye. We covered the general features of head and neck cancers in our article on symptoms of head and neck cancer.
- What was approved? Subcutaneous amivantamab (Rybrevant Faspro) as a single agent for recurrent or metastatic head and neck squamous cell carcinoma that has progressed after platinum and PD-1/PD-L1 immunotherapy. It is not approved for HPV-associated oropharyngeal cancer.
- Evidence: In the single-arm OrigAMI-4 trial, the response rate was 42% and the complete response rate 15%; in 56% of responders, the response lasted longer than 6 months. Median progression-free survival was 6.8 months and median overall survival 12.5 months.
- Limitation: This is an accelerated approval; a survival benefit has not yet been shown in a randomized trial. The comparison with cetuximab results from other trials is indirect.
- Side effects: Hypoalbuminemia, rash, paronychia, mouth sores and edema are common; grade 3 or higher side effects occurred in 60%. Watch for rare but serious pneumonitis.
Why does this matter?
Head and neck squamous cell carcinomas arise from the cells lining the mouth, tongue, larynx, pharynx and nasal cavity. Smoking and alcohol are the most important risk factors, while some cancers of the tonsils and base of the tongue are linked to HPV infection (HPV and head and neck cancer, smoking and cancer). When the disease comes back or spreads, first-line treatment is usually pembrolizumab, alone or with chemotherapy (first-line treatment).
The problem arises after these treatments. In patients who have received both platinum-based chemotherapy and immunotherapy and whose disease has progressed, the drugs available, such as cetuximab, methotrexate or taxanes, usually have response rates of only 10–24%. In the INTERLINK-1 trial, median progression-free survival with cetuximab in this patient group was 3.8 months and median overall survival 8.6 months. This is why the FDA describes this disease as "an aggressive disease with high unmet need."
What is Rybrevant Faspro (amivantamab)?
Rybrevant Faspro is a form of the two-armed (bispecific) antibody amivantamab combined with the enzyme hyaluronidase so that it can be given under the skin. Amivantamab targets two growth receptors on the tumor cell, EGFR and MET, at the same time and directs immune cells to the tumor. It was already used in lung cancer; in November 2026, it was also approved for head and neck cancer.
How does it work?
EGFR is a receptor that is overexpressed in the great majority of head and neck squamous cell carcinomas and drives the cell to grow. This is why EGFR drugs such as cetuximab have been used for years; however, tumors often develop resistance by receiving growth signals again through another receptor called MET. One arm of amivantamab binds to EGFR and the other to MET, blocking both pathways together. The tail portion of the antibody recruits immune cells such as NK cells and macrophages to the tumor cell. EGFR and MET are overexpressed in about 80–90% of HPV-unrelated tumors (amivantamab in lung cancer).
Figure 1 · How amivantamab works
Two receptors, one antibody and immune cells
The hyaluronidase enzyme in Rybrevant Faspro temporarily loosens the tissue under the skin, allowing the large volume of drug to be absorbed subcutaneously. In the PALOMA-3 trial in lung cancer, the subcutaneous form showed blood levels and efficacy similar to the intravenous form, while administration-related reactions fell from 66% to 13%.
Who does the approval cover?
Figure 2 · Scope of the approval
Who is it for, and who is it not for?
HPV-associated oropharyngeal cancers have a different biology from HPV-unrelated tumors and generally a better course. Because patients with oropharyngeal cancer shown to be HPV-associated by p16 testing were not included in the main analysis of OrigAMI-4, efficacy in this group is unknown; in a small first-line cohort, the response rate was also markedly lower in HPV-associated tumors. For this reason, it is important to know the HPV status of the tumor (p16 staining and, if needed, HPV testing) before treatment (new approaches in HPV16-positive head and neck cancer).
The OrigAMI-4 trial: what do the results show?
The approval is based on the first cohort of a phase 1b/2 trial called OrigAMI-4. The trial enrolled 102 patients with HPV-unrelated, recurrent or metastatic head and neck squamous cell carcinoma who had previously received both platinum-based chemotherapy and PD-1/PD-L1 immunotherapy. Half of the patients had received one prior line of treatment at this stage and the other half two; patients previously treated with an EGFR drug were excluded. Of the tumors, 47% originated in the oral cavity, 24% in the larynx, 16% in the hypopharynx and 14% in the oropharynx (HPV-unrelated). The results were presented at the ASCO meeting in June 2026 and published in the Journal of Clinical Oncology.
OrigAMI-4: response to subcutaneous amivantamab
102 patients with HPV-unrelated disease that progressed after platinum-based chemotherapy and immunotherapy; %.
The response rate by investigator assessment was 47%. Median time to response was 6.6 weeks. Median follow-up was 11.8 months; median duration of response has not yet been reached. Median progression-free survival was 6.8 months and median overall survival 12.5 months. This is a single-arm trial.
Figure 3 · Results rounded to 100 patients
How many patients responded?
Two points need attention when interpreting these results. First, the trial is single-arm; that is, amivantamab was not compared with another treatment within the same trial. The FDA's statement of "more than twice the response of approved therapies" is based on an indirect comparison with results from other trials. Second, early endpoints such as response rate and duration of response do not always translate into longer overall survival; this is why the FDA has required additional trials to confirm the benefit (how to read clinical trials).
Context: earlier results in the same patient group
OrigAMI-4 (colored) and the INTERLINK-1 control arm with cetuximab after platinum and immunotherapy (gray).
INTERLINK-1 is a randomized phase 3 trial in which cetuximab was used alone or with another drug; the values are taken from the control arm. The FDA noted that the response rate with approved therapies is about 20% or lower. Comparisons across different trials are indirect; patient populations, prior treatments and follow-up times differ.
What does accelerated approval mean?
The FDA's accelerated approval program allows a drug to come into use for serious diseases with limited treatment options based on early indicators such as response rate, without waiting for long-term results. These approvals are conditional: the company must complete trials that confirm the drug's real clinical benefit, such as on overall survival or quality of life. If the benefit is not confirmed, the approval can be withdrawn; in the past, the accelerated approvals of some cancer drugs were withdrawn in this way (an example of accelerated approval: dostarlimab).
Figure 4 · The accelerated approval process
From early evidence to full approval
How is it given?
Rybrevant Faspro is given as an injection under the skin of the abdomen. In the first cycle, it is given once a week on days 1, 8 and 15, and every 3 weeks after that; the dose is based on body weight. Treatment continues until the disease progresses or an unacceptable side effect develops. Premedications are given with the first doses to reduce the risk of reactions.
Figure 5 · Treatment schedule
Weekly in the first month, then every 3 weeks
What are the side effects?
The side effects of amivantamab largely stem from the two pathways it targets. Blocking EGFR leads to skin, nail and mouth side effects; blocking MET leads to hypoalbuminemia and the edema that comes with it. Because swallowing difficulty and weight loss are already common in patients with head and neck cancer, hypoalbuminemia makes nutritional support even more important (nutrition during treatment).
Most common side effects
OrigAMI-4, 102 patients; all grades, %.
Grade 3 or higher side effects occurred in 60% of patients; the dose was interrupted in 51% and reduced in 23%. The rate of drug-related treatment discontinuation was 8%. One patient had loss of life due to drug-related pneumonitis. All administration-related reactions were grade 1 or 2.
The warnings in the FDA prescribing information are: hypersensitivity and administration-related reactions, interstitial lung disease or pneumonitis, serious skin reactions, eye side effects and harm to an unborn baby. Serious side effects reported included bleeding (4.9%), swallowing difficulty, air leaking between the layers of the lung lining (pneumothorax) and pneumonitis. Six patients had side effect-related loss of life; one of these was due to drug-related pneumonitis.
Figure 6 · Coping with side effects
Six basic care tips
In amivantamab trials in lung cancer, using an oral antibiotic (doxycycline or minocycline), an antibiotic lotion on the face and body, and a moisturizer from the first weeks of treatment was shown to markedly reduce rashes. Although it seems reasonable to apply this kind of preventive care in head and neck cancer as well, it has not been studied separately in this patient group (skin side effects of cancer treatment).
Figure 7 · Symptoms you should report right away
Signs of a serious side effect
What comes next?
The use of amivantamab in earlier lines of head and neck cancer treatment is also being studied. In a small cohort presented at the ESMO meeting in October 2026, when subcutaneous amivantamab, pembrolizumab and carboplatin were used together in the first line, a response was seen in 77% of 22 patients with HPV-unrelated tumors; in 7 patients with HPV-associated tumors, this rate was 29%. The randomized phase 3 OrigAMI-5 trial, which will enroll about 500 patients, is under way to confirm these results.
Other new drugs targeting EGFR are also being developed for head and neck cancer. Petosemtamab, which targets EGFR and LGR5, is being evaluated with pembrolizumab in the first line in a phase 3 trial; chemotherapy-free combinations and new immunotherapy approaches are also being studied (petosemtamab and LiGeR-HN1, eftilagimod alfa, the effect of immunotherapy in head and neck cancer).
The situation in Türkiye
- As of November 2026, the head and neck cancer indication of Rybrevant Faspro does not have a marketing authorization in Türkiye and is not reimbursed by SGK. The authorization and reimbursement status of amivantamab in lung cancer also could not be verified at the time this article was prepared.
- An unlicensed drug can be obtained from abroad with a physician's report and TİTCK permission; however, this process can take a long time, and the cost may fall to the patient or depend on institutional approval (cancer drugs imported from abroad, access map for FDA-approved drugs in Türkiye).
- In Türkiye, cetuximab, methotrexate and taxanes can be used for head and neck cancer after platinum and immunotherapy; the reimbursement conditions for immunotherapy are defined in the SUT (SGK conditions for immunotherapy).
- Taking part in a clinical trial is an important option for this patient group; talk with your oncologist about suitable trials (early-phase trials).
- Quitting smoking has a positive effect on treatment response and quality of life in head and neck cancer; it matters even at an advanced stage (10 reasons to quit smoking).
Questions you can ask your doctor
- Is the HPV status (p16) of my tumor known; is this treatment suitable for me?
- Do the platinum and immunotherapy I received before meet the conditions of this approval?
- Is it possible for me to get this drug in Türkiye; if not, what options or clinical trials are available?
- What should I do before starting treatment to prevent skin, nail and mouth side effects?
- How will my nutrition and albumin level be monitored; can I get support from a dietitian?
- "If the FDA approved it, the drug has been proven to extend life." No. This is an accelerated approval; its effect on overall survival will be shown by confirmatory trials.
- "It can be used for all head and neck cancers." No. HPV-associated oropharyngeal cancer is not included; the approval is for patients whose disease progressed after platinum and immunotherapy.
- "If cetuximab didn't work, this won't work either." Unknown. Because OrigAMI-4 excluded patients previously treated with an EGFR drug, efficacy in this group is uncertain.
- "Because it is given under the skin, it has few side effects." No. The subcutaneous form only reduces administration-related reactions; skin, nail, albumin and lung side effects remain.
- "If a rash appears, treatment must be stopped." Usually not. A rash can be managed with early treatment; the decision belongs to the treatment team.
Frequently Asked Questions
- What is Rybrevant Faspro (amivantamab)?
- It is the subcutaneous form of amivantamab, a two-armed antibody that targets the EGFR and MET receptors on the tumor cell at the same time. It was used in lung cancer; on November 5, 2026, it received accelerated approval in the US for head and neck cancer.
- Who is amivantamab approved for in head and neck cancer?
- For adults with recurrent or metastatic head and neck squamous cell carcinoma whose disease progressed during or after platinum-based chemotherapy and immunotherapy. It is not approved for HPV-associated oropharyngeal cancer.
- How effective is amivantamab?
- In the 102-patient OrigAMI-4 trial, the tumor shrank markedly or disappeared in 42% of patients, and 15% had a complete response. Median overall survival was 12.5 months. Because the trial was single-arm, its effect on overall survival will be established by confirmatory trials.
- Is amivantamab available in Türkiye?
- As of November 2026, the head and neck cancer indication does not have a marketing authorization in Türkiye and is not reimbursed by SGK. An application to obtain it from abroad can be made with a physician's report and TİTCK permission; ask your oncologist about the current situation.
Glossary
- Squamous cell carcinoma
- Cancer arising from the flat (squamous) cells lining the mouth, larynx and pharynx; the most common type of head and neck cancer.
- Recurrent or metastatic
- Disease that has come back after treatment or spread to other organs.
- EGFR
- Epidermal growth factor receptor; a receptor that drives the cell to grow and is often overexpressed in head and neck cancers.
- MET
- A receptor involved in cell growth and spread that can serve as a resistance pathway to EGFR drugs.
- Bispecific antibody
- A two-armed antibody that can bind to two different targets at the same time.
- Hyaluronidase
- An enzyme that temporarily loosens the tissue under the skin so that large-volume drugs can be given subcutaneously.
- Accelerated approval
- A conditional FDA approval for serious diseases, based on early indicators and requiring a confirmatory trial.
- Overall response rate
- The proportion of patients whose tumor shrinks by a defined amount or disappears completely.
- p16 / HPV-associated oropharyngeal cancer
- Cancers of the tonsils and base of the tongue that are linked to the HPV virus; identified by p16 staining.
- Pneumonitis
- Inflammation of lung tissue; a rare but serious side effect of some cancer drugs.
DROZDOGAN Academy Commentary
Head and neck cancer after platinum and immunotherapy is one of the areas of oncology with the most limited options. This is why a 42% response rate and a 15% complete response rate stand out; however, enthusiasm needs to be balanced against the level of evidence.
⚡ Why it matters
For ten years, there had been no new drug approval for this patient group. Targeting EGFR and MET together offers a logical answer to the resistance problem seen with cetuximab.
✅ Strengths
A response rate confirmed by independent central review; a meaningful complete response rate; a hard-to-treat patient group, after immunotherapy and mostly with oral cavity primaries; fewer administration reactions with subcutaneous dosing.
⚠️ Limitations
A single-arm trial and indirect comparison; overall survival data are not randomized. The rate of grade 3 or higher side effects was 60%; of the six side effect-related losses of life, one was drug-related. Patients previously treated with an EGFR drug and HPV-associated tumors were excluded from the trial.
🩺 In practice
We see amivantamab as a promising option for our HPV-unrelated patients whose disease progresses after platinum and immunotherapy; however, because access in Türkiye is limited, we consider clinical trials and available options together. If treatment is started, we plan skin care and nutritional support from day one.
❓ Open questions
Will it extend overall survival in randomized trials? Is it effective in patients previously treated with cetuximab? Will the benefit be greater when it is used with immunotherapy in the first line? Can a biomarker that predicts response be found?
Bottom line: Subcutaneous amivantamab offers an important advance in response rates for HPV-unrelated head and neck cancer after platinum and immunotherapy. Its definitive place will be determined by the ongoing randomized trials (pembrolizumab, nivolumab, psychosocial effects of head and neck cancer).
- This article was prepared in November 2026.
- Approval information is taken from the FDA's announcements dated November 5, 2026; trial data from the OrigAMI-4 publication in the Journal of Clinical Oncology and its presentations; and first-line cohort data from a company announcement.
- Comparisons with other treatments are based on different trials and are indirect. The full text of the prescribing information had not been published at the time this article was prepared; dosing details are therefore given in general terms.
- Authorization and reimbursement information for Türkiye reflects the situation at the time this article was prepared. The illustrations are simplified. The Academy commentary is our own.
- This article is not medical advice; make your health decisions together with your doctor.
References
- U.S. Food and Drug Administration. FDA grants accelerated approval to a new treatment for head and neck squamous cell carcinoma. November 5, 2026. fda.gov
- U.S. Food and Drug Administration. FDA grants accelerated approval to amivantamab and hyaluronidase-lpuj for recurrent or metastatic head and neck squamous cell carcinoma. November 5, 2026. fda.gov
- Burtness B, Rosenberg AJ, 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. pmc.ncbi.nlm.nih.gov
- OncLive. FDA approves amivantamab and hyaluronidase for metastatic HNSCC. November 5, 2026. onclive.com
- Healio. Subcutaneous amivantamab induces durable responses in metastatic head, neck cancer. July 8, 2026. healio.com
- Johnson & Johnson. RYBREVANT FASPRO combination demonstrates 77% overall response rate in first-line treatment of patients with head and neck cancer (ESMO 2026). October 25, 2026. jnj.com
- U.S. Food and Drug Administration. FDA approves amivantamab and hyaluronidase-lpuj for subcutaneous injection (PALOMA-3). December 17, 2025. fda.gov
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