Subcutaneous Rybrevant Elicits Responses in Head and Neck Cancer Trial

Researchers in the global, multicenter OrigAMI-4 trial reported that subcutaneous Rybrevant (amivantamab) demonstrated promising antitumor activity in patients with recurrent or metastatic head and neck squamous cell carcinoma whose disease progressed after prior immunotherapy and platinum-based chemotherapy, addressing an unmet need for second- and third-line treatment options. Findings were published in Oral Oncology.

Rybrevant is a bispecific antibody designed to target epidermal growth factor receptor and mesenchymal epithelial transition receptor, both of which are overexpressed in 80% to 90% of head and neck squamous cell carcinoma cases and are associated with poorer prognosis. The preliminary results presented here come from Cohort 1 of the OrigAMI-4 trial, which evaluated subcutaneous Rybrevant as monotherapy in patients with human papillomavirus–unrelated recurrent or metastatic disease.

Main data that support the findings

At the July 1, 2025 data cutoff, 86 patients had received at least one dose of subcutaneous Rybrevant and were included in the safety population. The median age was 63.5 years, with a range of 30 to 81 years. Most patients were male (76%), and primary tumors were most commonly located in the oral cavity (49%). All patients had previously received systemic therapy for recurrent or metastatic disease, including anti–PD-(L)1 immunotherapy and platinum-based chemotherapy. Additionally, 45% had received prior taxane-based chemotherapy.

A total of 38 patients reached their second disease assessment or discontinued treatment and were included in the efficacy population. Among these patients, the confirmed objective response rate was 45%. This included one patient (3%) with a complete response and 16 patients (42%) with a partial response. Stable disease was observed in 45%, while 5% experienced progressive disease and 5% were not evaluable.

The confirmed clinical benefit rate, defined as complete response, partial response or durable stable disease at the second assessment, was 76%. A majority of patients, 82%, experienced tumor shrinkage in target lesions.

Among the 17 confirmed responders, the median time to response was 6.4 weeks, with a range of 5.7 to 18.3 weeks. The median duration of response was 7.2 months, and 47% of responders had a duration of response of six months or longer. At the time of analysis, 65% of confirmed responders remained on treatment.

Median progression-free survival was 6.8 months. Overall survival data were immature at the time of the data cutoff. Among the 38 patients in the efficacy population, 42% remained on Rybrevant treatment.

Trial details

OrigAMI-4 is a global, multicenter, open-label, multiarm, phase 1b/2 trial evaluating subcutaneous Rybrevant as monotherapy and in combination with standard-of-care therapies in patients with recurrent or metastatic head and neck squamous cell carcinoma.

Subcutaneous Rybrevant was administered in the abdomen. On Cycle 1 Day 1, patients received 1600 mg, or 2240 mg if body weight was 80 kg or higher. Weekly dosing continued during Cycle 1 at 2400 mg, or 3360 mg for those 80 kg or higher. Beginning Cycle 2 Day 1, dosing was given every three weeks at 2400 mg, or 3360 mg for those 80 kg or higher.

Imaging with CT or MRI was performed at screening, six weeks after the first dose and every six weeks for one year, then every nine weeks thereafter.

Safety

Among the 86 patients in the safety population, 92% experienced at least one treatment-emergent side effect. Grade 1 (mild) or 2 (moderate) side effects occurred in 45%, and grade 3 (severe) or higher side effects occurred in 47%. Serious side effects were reported in 34% of patients.

The most frequent side effects related to epidermal growth factor receptor inhibition included stomatitis (23%), dermatitis acneiform (20%), rash (19%) and paronychia (17%). Side effects associated with mesenchymal epithelial transition inhibition included hypoalbuminemia (31%) and peripheral edema (14%). Other common side effects included fatigue (31%), anemia (17%), hypocalcemia (15%), increased alanine aminotransferase (13%), nausea (13%), weight decreased (13%), decreased appetite (12%), dyspnea (12%) and lymphopenia (10%).

Grade 3 or higher side effects occurring in 5% or more of patients included dermatitis acneiform (7%) and anemia (6%). Administration-related reactions to subcutaneous Rybrevant were reported in 7% of patients and were grade 1 or 2.

Side effects led to dose interruption in 43%, dose reduction in 17% and discontinuation in 7%. Treatment-related discontinuation occurred in 2% of patients.

References

1. “Subcutaneous amivantamab monotherapy in patients with HPV-unrelated recurrent or metastatic head and neck squamous cell carcinoma from the OrigAMI-4 study” by Dr. Kevin J. Harrington, et al. Oral Oncology.

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