Dr Fayette on the Efficacy of Petosemtamab Plus Pembrolizumab in Metastatic HNSCC

Jerôme Fayette, MD, PhD, medical oncologist, Centre Léon Bérard, discusses findings from a phase 2 trial (NCT03526835) evaluating frontline petosemtamab (MCLA-158) plus pembrolizumab (Keytruda) in patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC).

This trial assessed the combination of petosemtamab and pembrolizumab in 24 efficacy-evaluable patients with previously untreated, recurrent or metastatic PD-L1–positive HNSCC with an ECOG performance status of 0 or 1 and measurable disease. The combination elicited an overall response rate (ORR) of 67% (95% CI, 45%-84%), including 1 complete response (CR), 12 partial responses (PRs), and 3 unconfirmed PRs. This ORR is numerically higher than the ORRs seen with TKIs and cetuximab (Erbitux) in this patient population, Fayette notes.

Response rates were similar between the HPV-positive and HPV-negative patient populations, as well as between the PD-L1–high and PD-L1–low populations, Fayette explains. In total, 42% of patients had a PD-L1 combined positive score (CPS) of 1 to 19, and 56% of patients had a PD-L1 CPS of 20 or higher. Among patients with low PD-L1 CPS, the ORR was 60%, with best responses of PD (n = 2), SD (n = 2), unconfirmed PR (n = 1), PR (n = 4), and CR (n = 1). In patients with high PD-L1 CPS, the ORR was 71%, with best responses of PD (n = 1), SD (n = 3), unconfirmed PR (n = 2), and PR (n = 8). Among patients with (57%) and without HPV type 16 (36%), the respective ORRs were 75% and 65%. Investigators observed no correlation between ORR and OS outcomes, Fayette notes.

Although longer follow-up data from this phase 2 trial are necessary to confirm the benefit of petosemtamab plus pembrolizumab in this patient population, current findings supported the initiation of a phase 3 registrational trial evaluating the combination vs pembrolizumab alone in the frontline setting, Fayette emphasizes. This trial is expected to begin at the end of 2024, Fayette concludes.