A Hit and a Miss for Merck’s Keytruda
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Merck posted a rare defeat Wednesday for its blockbuster Keytruda (pembrolizumab) in prostate cancer while simultaneously announcing a victory in biliary tract cancer.
A planned interim analysis of the Phase III KEYNOTE-991 trial in metastatic hormone-sensitive prostate cancer found that Keytruda, in combination with enzalutamide and androgen deprivation therapy, does not improve overall survival or radiographic progression-free survival (rPFS).
Based on the recommendations of an independent Data Monitoring Committee, Merck will discontinue the trial.
KEYNOTE-991 is a randomized and double-blinded trial with more than 1,250 patients enrolled. Participants were randomly assigned to receive Keytruda, given at 200-mg intravenous doses every three weeks, or placebo. All patients also received enzalutamide and androgen deprivation therapy.
Aside from efficacy, the trial assessed the safety of Keytruda in this patient population and found a profile consistent with previous studies. However, grade 3-5 adverse events and serious adverse events were more common in Keytruda-treated patients.
KEYNOTE-991 is not Keytruda’s first failure. In August 2022, the blockbuster drug also fell short of its dual primary endpoints in the Phase III KEYNOTE-921 study in metastatic castration-resistant prostate cancer. Keytruda could not elicit significant gains compared to placebo in terms of OS and rPFS. Patients in the study were also treated with prednisone and chemotherapy.
In mid-July 2022, Keytruda stumbled in another Phase III trial, this time in unresected, locally advanced head and neck squamous cell carcinoma. Merck’s drug was unable to improve event-free survival relative to placebo.
The company has other ongoing trials of Keytruda in prostate cancer, including KEYNOTE-199 and KEYNOTE-365, both Phase II, as well as KEYNOTE-641, a registrational Phase III study. All three are in mCRPC.
Keytruda Boosts Survival in Biliary Tract Cancer
Softening the prostate cancer blow, Keytruda aced its primary endpoint of OS in the Phase III KEYNOTE-966 trial assessing the drug in combination with gemcitabine and cisplatin for the first-line treatment of advanced or unresectable biliary tract cancer.
The safety profile for Keytruda in this study was consistent with what had been previously established.
The trial, a randomized and double-blinded study with more than 1,000 enrollees, compared the Keytruda combo with standard of care chemotherapy alone. Aside from OS, the study is also assessing progression-free survival, objective response rate, duration of response and safety.
Findings from KEYNOTE-966 will be presented at an upcoming medical conference, and the company plans to engage regulatory authorities with these data.