2026 ASCO Annual Meeting

Amivantamab Shows Rapid, Durable Responses in HPV-Unrelated Recurrent or Metastatic HNSCC

Edited by:
Ashton L. Stahl

Key Highlights

  • Subcutaneous amivantamab monotherapy produced a confirmed objective response rate of 47% in 102 patients.
  • Responses occurred rapidly, with a median time to initial response of 6.6 weeks.
  • Median duration of response was 7.2 months, and median progression-free survival was 6.8 months.
  • Treatment-emergent adverse events were mainly EGFR/MET-related; 6% discontinued because of treatment-related adverse events.

Subcutaneous amivantamab demonstrated rapid and durable responses in patients with HPV-unrelated recurrent or metastatic head and neck squamous cell carcinoma after disease progression on an immune checkpoint inhibitor and platinum-based chemotherapy, according to pivotal results from cohort 1 of the phase 1b/2 OrigAMI-4 study published in Journal of Clinical Oncology and presented at the 2026 ASCO Annual Meeting in Chicago, Illinois.1

The study evaluated amivantamab, an EGFR-MET bispecific antibody with immune cell–directing activity, as monotherapy in a population with poor prognosis after being on an immune checkpoint inhibitor and undergoing chemotherapy.1 In an interview with the Oncology Learning Network, Barbara Burtness, MD, FASCO, Yale Cancer Center, described OrigAMI-4 as a study of “subcutaneous administration of the EGFR-MET bispecific antibody amivantamab in patients with recurrent metastatic head and neck cancer.”2

Cohort 1 enrolled patients with recurrent or metastatic HNSCC whose disease progressed after a PD-(L)1 inhibitor and platinum-based chemotherapy. Prior anti-EGFR therapy was exclusionary. Patients received subcutaneous amivantamab at 1,600 mg or 2,240 mg for body weight at least 80 kg on cycle 1 day 1; 2,400 mg or 3,360 mg for body weight at least 80 kg on cycle 1 days 8 and 15; and then every 3 weeks. The primary endpoint was an objective response rate by RECIST v1.1. Secondary end points included the duration of response, progression-free survival, and safety.1

Study Findings

As of January 6, 2026, 102 patients had received at least 1 dose of subcutaneous amivantamab, and the cohort was fully enrolled. At a median follow-up of 9 months, the median patient age was 63 years; 77% of patients were men, and 67% had an ECOG performance status of 1. All patients had previously received a PD-(L)1 inhibitor and platinum-based chemotherapy.1

The confirmed objective response rate was 47% (48 of 102; 95% CI, 37%-57%), including 4 complete responses and 44 partial responses. Stable disease was reported in 39 patients, and 79% of patients experienced shrinkage of target lesions. Among confirmed responders, the median duration of response was 7.2 months (95% CI, 5.8 months to not estimable). The median time to initial response was 6.6 weeks, and the median progression-free survival was 6.8 months (95% CI, 5.2-8.2 months).1 Dr. Burtness noted that “the investigator-assessed response rate was 47%. This was confirmed at 42% by blinded independent central review.”2

Treatment-emergent adverse events were mainly EGFR/MET related. The most common adverse events, occurring in more than 25% of patients, were hypoalbuminemia, rash, dermatitis acneiform, paronychia, stomatitis, and fatigue. Administration-related reactions occurred in 13% of patients and were all grade 1 or 2. Six patients (6%) discontinued treatment because of treatment-related adverse events.1

Clinical Implications

According to the study authors, the findings suggest that subcutaneous amivantamab monotherapy demonstrated an objective response rate of 47%, with rapid and durable responses in patients with HPV-unrelated recurrent or metastatic HNSCC after progression on an immune checkpoint inhibitor and chemotherapy.1 Dr. Burtness also described the findings as showing “deep and durable responses for a very heavily pretreated patient population.”2

The authors stated that the safety profile and tolerability were consistent with prior reports.1

Expert Commentary

“SC amivantamab monotherapy demonstrated an ORR of 47%, with rapid and durable responses in [patients] with HPV-unrelated, R/M HNSCC after disease progression on an ICI and chemotherapy. The safety profile and tolerability are consistent with prior reports,” the researchers concluded.1

Reference

  1. Burtness B, Harrington KJ, Ji D, et al. Amivantamab in HPV-unrelated recurrent/metastatic head and neck squamous cell cancer after disease progression on immune checkpoint inhibitor and chemotherapy: pivotal results from the phase 1b/2 OrigAMI-4 study. J Clin Oncol. 2026;44(suppl 16):6008. doi:10.1200/JCO.2026.44.16_suppl.6008
  2. Burtness B. Amivantamab demonstrates durable responses in HPV-unrelated head and neck squamous cell carcinoma. Oncology Learning Network. Published June 5, 2026. Accessed June 23, 2026. https://www.hmpgloballearningnetwork.com/site/onc/videos/amivantamab-demonstrates-durable-responses-hpv-unrelated-head-and-neck-squamous