Johnson & Johnson: RYBREVANT FASPRO shows durable responses in advanced head and neck cancer
- OrigAMI-4 cohort 1 (n=102) of subcutaneous amivantamab and hyaluronidase-lpuj showed a confirmed ORR of 42% (15% CR); median duration of response not reached at 11.8-month follow-up.
- Median PFS was 6.8 months and median OS 12.5 months; median time to first response 6.6 weeks; treatment-related discontinuations 8%; common AEs included hypoalbuminemia 50%, rash 37%, paronychia 34%, dermatitis acneiform 34%, and administration-related reactions 15% (no Grade 3 or higher).
- A supplemental BLA has been submitted to the FDA after Breakthrough Therapy designation; Phase 3 OrigAMI-5 is ongoing to evaluate subcutaneous amivantamab with carboplatin and pembrolizumab as first-line therapy for recurrent/metastatic HNSCC.
Key results
In OrigAMI-4 cohort 1 (n=102), subcutaneous amivantamab plus hyaluronidase-lpuj achieved a confirmed ORR of 42% (15% complete response, 27% partial response) by BICR; median duration of response was not reached at a median follow-up of 11.8 months, median PFS was 6.8 months and median OS 12.5 months, with median time to first response 6.6 weeks.
Study population and dosing
Cohort 1 enrolled patients with recurrent or metastatic head and neck squamous cell carcinoma previously treated with PD-1/PD-L1 immunotherapy and platinum-based chemotherapy, excluding HPV-positive oropharyngeal cases; dosing was weekly during initial period then every three weeks after a loading phase.
Safety
The safety profile was consistent with prior reports and showed mostly Grade 1–2 treatment-related adverse events; common on-target AEs included hypoalbuminemia (50%), rash (37%), paronychia (34%) and dermatitis acneiform (34%); administration-related reactions occurred in 15% (no Grade ≥3 reported) and treatment-related discontinuations were 8%.
Mechanism and development status
Subcutaneous amivantamab is a bispecific agent targeting EGFR and MET while engaging the immune system; a supplemental BLA for head and neck cancer has been submitted to the FDA following Breakthrough Therapy designation, and a Phase 3 study (OrigAMI-5) is ongoing to test the agent with carboplatin and pembrolizumab as first-line therapy.
Source: J&J