The KEYLYNK-010 trial was evaluating a combination of pembrolizumab (Keytruda) and olaparib (Lynparza) in patients with metastatic castration-resistant prostate cancer who progressed following chemotherapy and either abiraterone acetate (Zytiga) or enzalutamide (Xtandi).
Merck is stopping its phase 3 KEYLYNK-010 trial (NCT03834519) analyzing a combination of pembrolizumab (Keytruda) and olaparib (Lynparza) in patients with metastatic castration-resistant prostate cancer (mCRPC) who progressed following chemotherapy and either abiraterone acetate (Zytiga) or enzalutamide (Xtandi) because of futility.
The decision is based on a recommendation from an independent Data Monitoring Committee (DMC) following a review of a planned interim analysis, which showed the combination did not provide an overall survival (OS) benefit compared with abiraterone acetate or enzalutamide, missing 1 of the trial’s primary end points. The dual primary endpoints of KEYLYNK-010 were OS and rPFS per Prostate Cancer Working Group-modified RECIST v1.1 as assessed by blinded independent central review. The secondary endpoints included time to initiation of the first subsequent anti-cancer therapy, objective response rate, duration of response and safety.
The trial enrolled 793 patients who were randomized into the experimental arm administered pembrolizumab 200 mg intravenously every 3 weeks for up to 35 cycles (approximately 2 years) in combination with olaparib 600 mg dosed as two 150-mg oral tablets twice daily until disease progression; or the control arm, which included patients previously treated with enzalutamide – abiraterone acetate 1000 mg dosed as two 500-mg or four 250-mg oral tablets once daily until disease progression plus prednisone 10 mg dosed as one 5-mg tablet twice daily until disease progression; as well as patients previously treated with abiraterone acetate–enzalutamide 160 mg dosed as four 40-mg oral tablets or capsules or two 80-mg tablets or capsules once daily until disease progression.
An earlier interim analysis found that pembrolizumab plus olaparib did not significantly improve radiographic progression-free survival (rPFS) compared with the control agents, which was the KEYLYNK-010 trial’s other primary end point. Although the toxicity profile of each individual agent was found consistent with what was observed in prior studies, the combination was associated with a higher incidence of adverse effects that were grades 3 to 5 in severity and a higher incidence of treatment-related serious toxicities versus the control group.
“There remains a significant unmet need for patients diagnosed with advanced prostate cancer, who have poor prognosis after not responding to initial therapy,” said Roy Baynes, MD, PhD, senior vice president and head of global clinical development, as well as chief medical officer at Merck Research Laboratories, in a press release. “Merck continues to evaluate the combination of [pembrolizumab] and [olaparib] in a range of cancers, and to research other [pembrolizumab]-based combinations for patients with advanced prostate cancer. We are grateful to the patients, their families, and the investigators who made this study possible.”
Merck announces KEYLYNK-010 trial evaluating KEYTRUDA (pembrolizumab) in combination with LYNPARZA (olaparib) in patients with metastatic castration-resistant prostate cancer to stop for futility. News release. Merck; March 15, 2022. Accessed March 15, 2022. https://bit.ly/3wqemRl