FDA OKs Breakthrough Status to Rybrevant Faspro in Head and Neck Cancer

The U.S. Food and Drug Administration (FDA) has granted breakthrough therapy designation to Rybrevant Faspro (amivantamab and hyaluronidase-lpuj) for adults in the U.S. with recurrent or metastatic head and neck squamous cell carcinoma that is human papillomavirus-unrelated and has progressed after platinum-based chemotherapy and a PD-1 or PD-L1 inhibitor, Johnson & Johnson announced in a news release.

The designation applies to the subcutaneous formulation of Rybrevant and Faspro when used as a single agent. According to the company, the decision was based on early clinical data showing rapid and durable responses in a heavily pretreated patient population.

Breakthrough therapy designation is intended to expedite the development and review of investigational medicines for serious or life-threatening conditions when preliminary clinical evidence suggests the therapy may demonstrate substantial improvement over available options on at least one clinically meaningful endpoint.

Head and neck squamous cell carcinoma is the most common type of head and neck cancer, accounting for more than 90% of cases and approximately 4.5% of all cancers worldwide. It develops in the mucosal linings of the oral cavity, oropharynx, hypopharynx and larynx. Around 75% of cases are HPV-negative, which is typically associated with a poorer prognosis and reduced response to treatment. Many patients ultimately experience advanced, recurrent or metastatic disease despite surgery, radiation, chemotherapy and immunotherapy.

Main data that support the findings

The breakthrough therapy designation is supported by results from the open-label phase 1b/2 OrigAMI-4 study. Data were presented during a mini-oral session at the 2025 European Society for Medical Oncology Congress.

In this study, subcutaneous Rybrevant demonstrated promising clinical activity in patients with HPV-unrelated recurrent or metastatic head and neck squamous cell carcinoma who had previously received platinum-based chemotherapy and PD-1 or PD-L1 immunotherapy. The company reported rapid and durable responses in this heavily pretreated group.

HPV-unrelated recurrent or metastatic head and neck squamous cell carcinoma is characterized by high rates of epidermal growth factor receptor expression and mesenchymal-epithelial transition pathway overexpression. Subcutaneous Rybrevant is designed to target both pathways while also activating the immune system. The clinical activity observed so far supports further evaluation in this population, where treatment options remain limited after prior therapies.

Based on these findings, the therapy is now being studied further in a phase 3 trial to better understand its potential role in earlier lines of treatment.

Trial details

OrigAMI-4 is an open-label phase 1b/2 study evaluating Rybrevant Faspro in recurrent or metastatic head and neck squamous cell carcinoma. The study includes five cohorts.

Cohort 1 evaluated Rybrevant Faspro as a single agent in patients with HPV-unrelated recurrent or metastatic disease who had previously received platinum-based chemotherapy and PD-1 or PD-L1 immunotherapy. Patients who had received prior anti-EGFR therapy were excluded.

Rybrevant Faspro was administered every three weeks at a dose of 2400 mg, or 3360 mg for patients weighing 80 kg or more. The primary endpoint is overall response rate, assessed by blinded independent central review using RECIST v1.1 criteria.

Subcutaneous Rybrevant is also being evaluated in the ongoing phase 3 OrigAMI-5 study. This trial is assessing subcutaneous Rybrevant in combination with Keytruda (pembrolizumab) and Paraplatin (carboplatin) compared with 5-fluorouracil plus Keytruda and platinum-based chemotherapy, either cisplatin or Paraplatin, as a first-line treatment for patients with HPV-unrelated recurrent or metastatic head and neck squamous cell carcinoma, regardless of PD-L1 expression.

Safety

The safety profile of Rybrevant Faspro and Rybrevant has been established in studies in non-small cell lung cancer.

Rybrevant Faspro is contraindicated in patients with known hypersensitivity to hyaluronidase or any of its excipients.

Hypersensitivity and administration-related reactions can occur with Rybrevant Faspro. Signs and symptoms may include shortness of breath, flushing, fever, chills, chest discomfort, low blood pressure and vomiting. The median time to onset is approximately 2 hours. Premedication with antihistamines, antipyretics and glucocorticoids is recommended, and patients should be monitored during injection in settings equipped for cardiopulmonary resuscitation.

Rybrevant and Rybrevant Faspro can also cause severe and fatal interstitial lung disease or pneumonitis. Patients should be monitored for new or worsening symptoms such as shortness of breath, cough or fever. Treatment should be withheld in patients with suspected interstitial lung disease or pneumonitis and permanently discontinued if confirmed.

When used in combination with Lazcluze, Rybrevant Faspro and Rybrevant can cause serious and fatal venous thromboembolic events, including deep vein thrombosis and pulmonary embolism. Prophylactic anticoagulation is recommended for the first four months of treatment, and patients should be monitored for signs and symptoms of blood clots.

Dermatologic side effects are common and can include severe rash, dermatitis acneiform, itching and dry skin. Patients are advised to limit sun exposure during treatment and for two months after, and to use protective clothing and broad-spectrum sunscreen. Supportive care and dose adjustments may be needed depending on severity.

Ocular toxicity, including keratitis, blepharitis, dry eye symptoms and blurred vision, has also been reported. Patients with new or worsening eye symptoms should be referred promptly to an ophthalmologist.

Based on animal studies, these therapies can cause fetal harm. Pregnancy status should be verified before starting treatment, and patients of reproductive potential should use effective contraception during treatment and for the recommended period after the last dose.

References

1. “RYBREVANT FASPRO™ (amivantamab and hyaluronidase-lpuj) receives U.S. FDA Breakthrough Therapy Designation for patients with advanced head and neck cancer” News Release. Johnson & Johnson.

Editor's note: This article is for informational purposes only and is not a substitute for professional medical advice, as your own experience will be unique. Use this article to guide discussions with your oncologist. Content was generated with AI and reviewed by a human editor.

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