Johnson & Johnson (NYSE: JNJ) reported pivotal Phase Ib/II data showing that subcutaneous amivantamab and hyaluronidase-lpuj (Rybrevant Faspro) produced a 42% confirmed overall response rate in patients with recurrent or metastatic head and neck squamous cell carcinoma who had already progressed on immunotherapy and platinum-based chemotherapy. The results are significant since the targeted patient population has limited treatment options after progression on both immunotherapy and platinum chemotherapy, where response rates with available therapies have historically remained low. The bispecific antibody's dual EGFR and MET targeting mechanism is central to its rationale in this setting, where resistance to prior treatment is common and single-pathway inhibition has historically yielded limited benefit.
The results, presented in an ASCO oral session and simultaneously published in the Journal of Clinical Oncology, support a supplemental Biologics License Application currently under FDA review.
Trial data
The OrigAMI-4 study is an open-label Phase Ib/II trial enrolling patients with recurrent or metastatic HNSCC across multiple cohorts. Cohort 1, which generated the pivotal readout, enrolled 102 patients who had received prior PD-1/PD-L1 immunotherapy and platinum-based chemotherapy; patients with HPV-positive oropharyngeal cancer or prior anti-EGFR therapy were excluded. Amivantamab and hyaluronidase-lpuj was administered subcutaneously on a weekly loading schedule followed by dosing every three weeks, with weight-based adjustments. The primary endpoint was investigator-assessed overall response rate per RECIST v1.1, with responses confirmed by blinded independent central review.
By blinded independent central review, the confirmed overall response rate was 42% (95% CI, 32–52), with complete responses in 15% of patients — more than one-third of all responders — and partial responses in 27%. The clinical benefit rate reached 63% (95% CI, 53–72), and median time to first response was 6.6 weeks. At a median follow-up of 11.8 months, median duration of response had not yet been reached, a finding that distinguishes this dataset from the shallow, short-lived responses typically seen with salvage-line agents in this tumor type. Median progression-free survival was 6.8 months and median overall survival was 12.5 months. The safety profile was consistent with prior amivantamab experience: most treatment-related adverse events were Grade 1 or 2, driven by on-target EGFR and MET inhibition, with hypoalbuminemia (50%), rash (37%), paronychia (34%), and dermatitis acneiform (34%) the most common. Administration-related reactions occurred in 15% of patients, with no Grade 3 or higher events. Treatment-related discontinuations were low at 8%. The data were presented in an oral session at the 2026 American Society of Clinical Oncology Annual Meeting and simultaneously published in the Journal of Clinical Oncology.