J&J Reports Strong Tumour Responses With RYBREVANT FASPRO

Johnson & Johnson reported a confirmed overall response rate (ORR) of 77% with subcutaneous RYBREVANT FASPRO™ (amivantamab and hyaluronidase-lpuj), pembrolizumab and carboplatin in previously untreated patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC), excluding those with human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC).

The findings came from Cohort 5 of the Phase 1b/2 OrigAMI-4 study (NCT06385080) and were presented at the European Society for Medical Oncology (ESMO) Congress 2026. The results support further investigation of the combination in the Phase 3 OrigAMI-5 study. However, the 77% response rate was based on a small subgroup and does not establish comparative efficacy against existing treatments.

Clinical Findings: A 77% Response Rate

The study evaluated subcutaneous amivantamab with pembrolizumab, a programmed death-1 (PD-1) inhibitor, and up to six cycles of carboplatin. Eligible patients had previously untreated recurrent or metastatic HNSCC and a programmed death-ligand 1 (PD-L1) combined positive score (CPS) of at least 1.

Of the 30 patients who received treatment, 29 were included in the efficacy analysis. Among the 22 patients with HNSCC other than HPV-associated OPSCC, the confirmed ORR was 77% (95% confidence interval [CI], 55–92). Complete responses occurred in 14% of patients, while 64% had partial responses. The primary endpoint was investigator-assessed ORR using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1).

Responses occurred at a median of 9.4 weeks. At a median follow-up of 10.6 months, 65% of responses remained ongoing. Four patients (18%) had stable disease, and one (5%) had progressive disease. Median overall survival had not been reached, while 77% of patients in this subgroup were alive at one year.

Among the seven patients with HPV-associated OPSCC, the ORR was 29% (95% CI, 4–71). The wide confidence interval reflects substantial uncertainty around this estimate, given the small number of patients.

How Does the Combination Work?

Amivantamab is a bispecific antibody targeting epidermal growth factor receptor (EGFR) and mesenchymal-epithelial transition (MET), proteins involved in tumour growth and signalling. It can also engage immune effector mechanisms. RYBREVANT FASPRO combines amivantamab with hyaluronidase-lpuj to enable subcutaneous administration.

Pembrolizumab blocks PD-1-mediated immune suppression, while carboplatin is a platinum-based chemotherapy agent that damages tumour-cell DNA. The combination targets different aspects of tumour biology and immune regulation. However, because the agents were evaluated together, the study cannot establish the independent contribution of each drug to the observed responses.

Safety and Administration

Johnson & Johnson reported that the safety profile was consistent with the known profiles of the individual agents. The most common adverse events were anaemia (73%), hypoalbuminaemia (63%), thrombocytopenia (63%) and stomatitis (57%).

Administration-related reactions associated with subcutaneous amivantamab occurred in 13% of patients, with no Grade 3 or higher reactions reported. Following the initial treatment period, administration was scheduled every three weeks, and subcutaneous administration took five minutes or less.

These findings provide information on the regimen’s tolerability in the studied cohort. The small sample size and limited follow-up, however, restrict conclusions about less common or longer-term safety risks.

Phase 3 Evaluation and Regulatory Status

The Phase 3 OrigAMI-5 study will further evaluate the combination and help determine whether the early-phase efficacy findings are reproducible. Larger-scale evidence will be needed to clarify the regimen’s potential clinical role in first-line HNSCC.

Johnson & Johnson also stated that an application for RYBREVANT FASPRO in later-line head and neck cancer was under Priority Review with the US Food and Drug Administration at the time of its announcement. This regulatory development is separate from the investigational first-line combination described here.

Clinical Interpretation

Cohort 5 of OrigAMI-4 showed a confirmed ORR of 77% with subcutaneous amivantamab, pembrolizumab and carboplatin in 22 patients with HNSCC other than HPV-associated OPSCC. The response rate and the proportion of responses ongoing at follow-up indicate antitumour activity in this subgroup.

The findings remain preliminary. The small efficacy population, wide confidence interval and absence of comparative evidence prevent conclusions about superiority over existing first-line options. The results also do not establish that the regimen improves overall survival. Phase 3 evaluation will be important to determine the durability and clinical relevance of the observed responses.

Reference

RYBREVANT FASPRO™ (amivantamab and hyaluronidase-lpuj) combination demonstrates 77% overall response rate in first-line treatment of patients with advanced head and neck cancer, Johnson and Johnson, 25 October 2026

A Study of Amivantamab Alone or in Addition to Other Treatment Agents in Participants with Head and Neck Cancer (OrigAMI-4), ClinicalTrials.gov ID NCT06385080