The phase 3 KEYNOTE-921 trial did not meet its coprimary end points of overall survival and radiographic progression-free survival in patients with metastatic castration-resistant prostate cancer.
Pembrolizumab (Keytruda) in addition to docetaxel did not demonstrate a statistically significant improvement in overall survival (OS) and radiographic progression-free survival (rPFS), missing the coprimary end points of the phase 3 KEYNOTE-921 trial examining the combination in patients with metastatic castration-resistant prostate cancer (mCRPC) (NCT03834506).1
While modest trends towards improvements in OS and rPFS for patients who received the combination were seen when compared with chemotherapy alone, these results did not meet statistical significance per the pre-specified statistical plan.
The results also indicated that the safety profile of pembrolizumab was consistent with what has been reported in previous trials, and investigators plan to present full data of the trial at an upcoming medical meeting.
“Results from this study serve as an important reminder that metastatic prostate cancer remains very difficult to treat, and more research is needed. We will continue to advance our clinical development program to evaluate pembrolizumab-based combinations and novel candidates for patients with this disease,” said Eliav Barr, MD, senior vice president, head of global clinical development and chief medical officer of Merck Research Laboratories, in a press release. “We are grateful to the patients and investigators for their participation in this study.”
In the randomized, double-blind, phase 3 KEYNOTE-921 trial, pembrolizumab in combination with docetaxel and prednisone was evaluated vs placebo plus chemotherapy and prednisone.2The purpose of this study was to assess both the efficacy and safety of the combination in this patient population.
Patients with mCRPC who had not received chemotherapy for mCRPC but whose disease had progressed on or was intolerant to a next-generation hormonal agent were enrolled in the trial. Eligibility was open to patients with ongoing androgen deprivation with serum testosterone level below 50 ng/dL, an ECOG performance status of 0 or 1, and they must provide a newly obtained core or excisional biopsy from soft tissue not previously irradiated or bone biopsy in the case of bone only or bone predominant disease. Additionally, patients who were receiving bone resorptive therapy including bisphosphonate, denosumab, and others, must have been on stable doses prior to randomization.
A total of 1030 patients were enrolled and randomly assigned to receive either 200 mg of pembrolizumab every 3 weeks for up to approximately 2 years plus 75 mg/m2 of docetaxel and 5 mg of prednisone twice daily for approximately 7 months (experimental arm) or placebo plus docetaxel and prednisone on the same schedule (control arm). On day 1 of each of the 3-week cycles, patients were given oral dexamethasone at 8 mg at 12 hours, 3 hours, and 1 hour prior to docetaxel administration.
The coprimary end points of the study were OS and rPFS with secondary end points including time to initiation of the first subsequent anti-cancer therapy, prostate-specific antigen response rate, objective response rate, and duration of response.
Other than this trial, the company has several additional studies evaluating pembrolizumab alone and in combination with other anti-cancer therapies in prostate cancer. These studies include the phase 2 KEYNOTE-199 (NCT02787005) trial, phase 2 KEYNOTE-365 (NCT02861573) trial, and the phase 3 registrational KEYNOTE-641 (NCT03834493) and KEYNOTE-991 (NCT04191096) trials.