Dr Mehra on the Use of Amivantamab Plus Pembrolizumab and Carboplatin in HNSCC

“In OrigAMI-5, with the addition of carboplatin, enrollment is allowed for patients irrespective of PD-L1 expression. This gives the opportunity for more patients to be on study and receive the combination therapy.”

Ranee Mehra, MD, director of Head and Neck Medical Oncology and a professor of medicine at the Marlene and Stewart Greenebaum Comprehensive Cancer Center at the University of Maryland Medical System, discussed the addition of pembrolizumab (Keytruda) to amivantamab and hyaluronidase-lpuj (Rybrevant Faspro; subcutaneous amivantamab) for the treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC).

Mehra began by noting that patients with this disease state often experience many symptoms, emphasizing the importance of developing treatment options that elicit deep responses, which may also improve quality of life (QOL). Data from cohort 2 of the phase 1/2 OrigAMI-4 study (NCT06385080) that Mehra presented at the 2026 Multidisciplinary Head and Neck Cancers Symposium showed that the combination of subcutaneous amivantamab and pembrolizumab elicited durable responses and tumor shrinkage among patients with treatment-naive, human papillomavirus–unrelated, recurrent or metastatic HNSCC (n = 39). However, she explained that enrollment to cohort 2 of this trial required patients to have a PD-L1 expression level of at least 1.

The phase 3 OrigAMI-5 trial (NCT07276399) is investigating subcutaneous amivantamab plus pembrolizumab and carboplatin vs standard-of-care platinum-based chemotherapy, pembrolizumab, and 5-fluorouracil in patients with previously untreated, recurrent or metastatic HNSCC regardless of PD-L1 expression status. Mehra emphasized that these broader enrollment criteria allow for more patients to receive subcutaneous amivantamab–based combination therapy for this disease.

OrigAMI-5 is currently enrolling. Additional enrollment criteria include an ECOG performance status of 0 or 1, as well as measurable disease per RECIST 1.1 criteria. Overall survival and objective response rate will serve as the coprimary end points. Key secondary end points will include progression-free survival, duration of response, safety, and QOL outcomes.