The FDA is currently reviewing Merck’s sBLA for Keytruda in head and neck cancer, with a target action date of June 23.
Merck’s blockbuster PD-1 inhibitor Keytruda elicited significant survival benefits in certain patients with head and neck cancer in the Phase III KEYNOTE-689 study, according to an interim readout.
These data, presented Sunday at the 2025 Annual Meeting of the American Association for Cancer Research (AACR), demonstrated that perioperative Keytruda improves event-free survival (EFS) by 27% in the study’s intention-to-treat population, as compared with a perioperative radiotherapy regimen. KEYNOTE-689 defines EFS as the first case of radiographic progression, recurrence, local or distant progression or death due to any cause. Patients in the trial were treated for head and neck squamous cell carcinoma (HNSCC).
Subgroup analyses showed that Keytruda’s efficacy in this indication scales according to PD-L1 expression, as measured by the Combined Positive Score (CPS). In patients with high expression levels of PD-L1, Keytruda lowered the likelihood of EFS events by 34% versus perioperative radiotherapy.
Merck has already filed a supplemental Biologics License Application for Keytruda in this indication, for which the FDA has a deadline of June 23.
In a Monday morning note, analysts at William Blair said the results were in line with their expectations but cautioned that the market impact might be small. “While this benefit is likely to support adoption of Keytruda in the perioperative HNSCC setting,” they wrote, “we maintain our view that this ultimately has less than a 10% impact on the metastatic HNSCC population.”
An April 16 note from William Blair stated that the readout will nevertheless affect other potential for uptake in the space for other companies with similar outlooks, such as Merus’ bispecific antibody petosemtamab and Exelixis’ oral tyrosine kinase inhibitor zanzalintinib. In that note, the analysts had projected that risk reduction in KEYNOTE-689 would be “likely lower than 40%,” which was borne out by the readout.
On Sunday, Merck also reported that Keytruda significantly improved major pathological response, a key secondary endpoint, in the intention-to-treat population—a treatment benefit of 9.3% versus adjuvant radiotherapy alone. Overall survival trended in Keytruda’s favor, though only in a subset of patients, and with a magnitude of effect that fell short of significance. KEYNOTE-689 will continue to follow patients for OS analysis.
