The U.S. Food and Drug Administration has granted Breakthrough Therapy Designation to amivantamab plus hyaluronidase-lpuj (Rybrevant Faspro), a subcutaneous treatment for adults with recurrent or metastatic, HPV-unrelated head and neck squamous cell carcinoma (HNSCC) whose disease has worsened after platinum-based chemotherapy and immunotherapy. This designation is based on results from the Phase 1b/2 OrigAMI-4 study.
In the trial, the treatment showed strong activity. The overall response rate was 45%, which is higher than what is typically seen with current treatments. The clinical benefit rate reached 76%, and 82% of patients had tumor shrinkage. Responses happened quickly, with a median time to first response of about 6.4 weeks.
The subcutaneous form makes the drug easier to give and was generally well tolerated. Only 7% of patients had mild administration-related reactions. Common side effects included skin rash, fatigue, and anemia. Based on these encouraging results, a larger Phase 3 trial, OrigAMI-5, is now underway to test this treatment in newly diagnosed metastatic patients in combination with pembrolizumab and chemotherapy.