Johnson & Johnson announced promising Phase 1b/2 results for subcutaneous amivantamab in patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC), demonstrating a 45% overall response rate in a patient population with historically poor outcomes. The data were presented at the European Society for Medical Oncology (ESMO) 2025 Congress.
Addressing Critical Unmet Need
Patients with R/M HNSCC face limited treatment options after disease progression on checkpoint inhibitors and platinum-based chemotherapy. Current available therapies typically achieve response rates of only 10 to 24 percent, with median survival ranging from 6 to 9 months. The situation is particularly challenging for patients with HPV-unrelated disease, who may experience even shorter survival times.
"Patients with recurrent or metastatic head and neck cancer face an aggressive disease that significantly impacts their quality of life," said Professor Kevin Harrington, MBBS, Ph.D., Professor in Biological Cancer Therapies at The Institute of Cancer Research, Royal Marsden Hospital, London, UK, and primary study investigator. "These results represent one of the most encouraging response rates we've seen in this difficult-to-treat setting, with durability that could meaningfully extend the time patients live without their disease progressing."
Strong Efficacy Results
In Cohort 1 of the OrigAMI-4 study, subcutaneous amivantamab achieved an overall response rate of 45% in 38 efficacy-evaluable patients with HPV-unrelated R/M HNSCC who had progressed on or after PD-1 or PD-L1 checkpoint inhibitor and platinum-based chemotherapy (95% confidence interval, 29-62).
The treatment demonstrated rapid onset of action, with a median time to first response of 6.4 weeks (range, 5.7-18.3 weeks). Responses proved durable, with a median duration of response of 7.2 months (95% CI, 5.3-not estimable). Tumor shrinkage of target lesions was observed in 82% of patients after 8.3 months of follow-up.
Median progression-free survival reached 6.8 months (95% CI, 4.2-9.0), while median overall survival had not yet been reached (95% CI, 7.7-not estimable).
Targeting Key Tumor Drivers
The therapeutic approach leverages the fact that epidermal growth factor receptor (EGFR) and MET are overexpressed in 80 to 90 percent of HNSCC tumors. RYBREVANT®, the world's first bispecific antibody approved for lung cancer, inhibits both EGFR and MET while also activating the immune system to attack cancer cells.
"These data highlight the broader potential of RYBREVANT-based therapies across solid tumors where the EGFR and/or MET pathways are activated," said Kiran Patel, Vice President, Global Head, Solid Tumor Clinical Development and Diagnostics, Johnson & Johnson Innovative Medicine. "By targeting EGFR and MET while also engaging the immune system, subcutaneous amivantamab could provide new options for more patients who have few effective treatments."
Favorable Safety Profile
The safety-evaluable population included 86 patients who received at least one dose of subcutaneous amivantamab monotherapy. The safety profile was consistent with prior subcutaneous amivantamab monotherapy studies, with no new safety signals observed.
The most common treatment-emergent adverse events were fatigue (31%), hypoalbuminemia (31%), and stomatitis (23%). Administration-related reactions occurred in 7% of patients, all mild to moderate (grade 1-2), with no severe events. Treatment discontinuation due to treatment-related adverse events occurred in only 2% of patients.
Convenient Administration
The subcutaneous formulation represents a significant advancement in patient convenience. The treatment can be delivered via a five-minute manual injection, offering substantial advantages over intravenous RYBREVANT® administration. This investigational formulation combines the bispecific antibody amivantamab with recombinant human hyaluronidase PH20 (rHuPH20), part of Halozyme's ENHANZE® drug delivery technology.
Moving Forward to Phase 3
Based on these encouraging results, Johnson & Johnson is initiating the Phase 3 OrigAMI-5 study, which will evaluate first-line subcutaneous amivantamab with pembrolizumab and carboplatin versus 5-fluorouracil plus pembrolizumab and platinum-based chemotherapy in patients with HPV-unrelated R/M HNSCC.
Study Design and Patient Population
The OrigAMI-4 study is an open-label Phase 1b/2 trial evaluating subcutaneous amivantamab in R/M HNSCC across five cohorts. Cohort 1 specifically studied the treatment as monotherapy in patients with HPV-unrelated R/M HNSCC who had received prior platinum-based chemotherapy and PD-1/PD-L1 immunotherapy. Patients with prior anti-EGFR therapy were excluded.
Subcutaneous amivantamab was administered every three weeks at 2400 mg, or 3360 mg for patients weighing 80 kg or more. The primary endpoint was overall response rate, assessed by blinded independent central review using RECIST v1.1.
These findings add to the growing evidence supporting RYBREVANT®-based treatments across multiple solid tumors, including non-small cell lung cancer, colorectal cancer, and HNSCC, potentially expanding treatment options for patients with limited therapeutic alternatives.
