Dr Swiecicki on First-Line Amivantamab Plus Pembrolizumab and Carboplatin in HNSCC

“At the end of the day, survival is what we really care about for these patients, and so this points to a potentially big breakthrough in therapy in the near future with the use of EGFR-targeted agents.”

Paul L. Swiecicki, MD, a clinical associate professor in the Division of Hematology/Oncology at the University of Michigan Rogel Cancer Center, as well as co-director of the Experimental Therapeutics/Phase 1 Research Team and associate director of the Oncology Clinical Trial Support Unit at the University of Michigan, discussed data from cohort 5 of the phase 1b/2 OrigAMI-4 trial (NCT06385080) evaluating subcutaneous amivantamab and hyaluronidase-lpuj (Rybrevant Faspro) plus pembrolizumab (Keytruda) and carboplatin as first-line therapy for recurrent/metastatic head and neck squamous cell carcinoma (HNSCC).

EGFR has long been a treatment target in HNSCC with cetuximab (Erbitux) and other EGFR inhibitors, but MET is a known escape pathway from cetuximab, and prior MET inhibitors showed limited activity, Swiecicki explained. Dual EGFR/MET targeting therefore holds promise across lines of therapy, he said.

Cohort 5 enrolled patients who had not received a PD-1/PD-L1 or EGFR inhibitor and whose disease had not recurred within 6 months of platinum-based chemotherapy, according to Swiecicki. All patients had an ECOG performance status of 0 or 1 and a PD-L1 combined positive score (CPS) of at least 1; both HPV-associated oropharyngeal and HPV-unrelated disease were eligible.

Data presented at the 2026 ESMO Congress showed a confirmed objective response rate (ORR) of 77% (95% CI, 55%-92%) in patients with HPV-unrelated disease (n = 22), including a 14% complete response rate. At a median follow-up of 10.6 months, median overall survival was not reached, and 77% of patients were alive at 1 year. Despite the limits of cross-trial comparisons, Swiecicki noted that historical ORRs are 14% to 20% with pembrolizumab alone and in the 30% range with chemoimmunotherapy.

Chemotherapy-related myelosuppression was the most common toxicity, he said. Acneiform rash and edema occurred secondary to amivantamab, and immune-related toxicities matched those expected with single-agent pembrolizumab, Swiecicki added.

Subcutaneous amivantamab monotherapy is under FDA priority review in later-line HNSCC, Swiecicki noted. The phase 3 OrigAMI-5 trial (NCT07276399) is comparing subcutaneous amivantamab plus pembrolizumab and up to 6 cycles of carboplatin vs carboplatin, 5-fluorouracil, and pembrolizumab in HPV-unrelated disease regardless of PD-L1 status, including a CPS of 0. These results will be especially interesting in the context of other EGFR-directed bispecific antibodies in development, Swiecicki concluded.