Dr Mehra on the Design of the OrigAMI-5 Trial of Amivantamab-Based Therapy in HNSCC

“We’ll learn a lot from further investigation, and as we learn more in the recurrent/metastatic setting, it gives us an opportunity to bring active agents into the perioperative setting, which will also be useful.”

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 how the ongoing phase 3 OrigAMI-5 trial (NCT07276399) may address an unmet need for patients with treatment-naive recurrent or metastatic head and neck squamous cell carcinoma (HNSCC).

OrigAMI-5 is evaluating amivantamab (Rybrevant) plus pembrolizumab (Keytruda) and carboplatin compared with pembrolizumab plus 5-fluorouracil and carboplatin or cisplatin in this population. Mehra noted that the control regimen was FDA approved in 2019 for the frontline treatment of patients with metastatic or unresectable recurrent HNSCC, irrespective of PD-L1 expression level, based on findings from the phase 3 KEYNOTE-048 trial (NCT02358031). Thus, she explained that head and neck oncologists have experience using the control combination. However, she emphasized that the shift to single-agent platinum chemotherapy in the investigational arm has opened the door to studying the efficacy and safety of a regimen that is potentially less cytotoxic than the KEYNOTE-048 combination.

Overall, several agents are making their way through development stages for patients with head and neck cancer, Mehra explained. In addition to amivantamab, ficerafusp alfa (BCA101) and petosemtamab (MCLA-158) are also under investigation in phase 3 trials. Notably, the phase 2/3 FORTIFI-HN01 trial (NCT06788990) is evaluating first-line ficerafusp alfa plus pembrolizumab in patients with human papillomavirus–negative recurrent or metastatic HNSCC. Additionally, the LiGeR-HN1 study (NCT06525220) is investigating first-line petosemtamab plus pembrolizumab in patients with recurrent or metastatic, PD-L1–positive HNSCC. If these agents show activity in the recurrent/metastatic setting, they may then be studied in the perioperative setting, potentially further expanding the treatment arsenal for many patients, she concluded.