Merck yesterday announced that it will stop the phase-III 3 Keylynk-010 trial investigating Keytruda, Merck’s anti-PD-1 therapy, in combination with Lynparza, a PARP inhibitor, for the treatment of patients with metastatic Castration-Resistant Prostate Cancer (mCRPC) who progressed after treatment with chemotherapy and either abiraterone acetate or enzalutamide, the company notified in a statement.
Merck is discontinuing the study following the recommendation of an independent Data Monitoring Committee (DMC) after the DMC reviewed data from a planned interim analysis. At the interim analysis, the combination of Keytruda and Lynparza did not demonstrate a benefit in the overall survival, one of the study’s dual primary endpoints, compared to the control arm of either abiraterone acetate or enzalutamide. The trial’s other dual primary endpoint, radiographic progression free survival, was evaluated at an earlier interim analysis and did not demonstrate improvement compared to the control arm, added the statement.
It also said that the safety profile of Keytruda, in combination with Lynparza, in this trial was consistent with that observed in previously reported studies for the individual therapies. However, the combination was associated with a higher incidence of grade 3-5 adverse events and drug-related serious adverse events, compared to the control arm. Merck will inform study investigators of the recommendation from the DMC and advise patients in the study to speak to their physician regarding treatment. Data from this study will be presented at an upcoming scientific congress.
“There remains a significant unmet need for patients diagnosed with advanced prostate cancer, who have a poor prognosis after not responding to initial therapy. Merck continues to evaluate the combination of Keytruda and Lynparza in a range of cancers, and to research other Keytruda-based combinations for patients with advanced prostate cancer……,” said Dr Roy Baynes, Senior Vice President and Head, Global Clinical Development, Chief Medical Officer, Merck Research Laboratories, in the statement.
Merck has an extensive clinical development programme in prostate cancer evaluating Keytruda as monotherapy and in combination with Lynparza and other anti-cancer therapies. Ongoing trials evaluating Keytruda include the phase-II trials Keynote-199 and Keynote-365, and phase-III registrational trials Keynote-641, Keynote-921 and Keynote-991. In collaboration with AstraZeneca, Merck is evaluating Lynparza in combination with abiraterone in the phase-III PROpel trial. Keylynk-010 is one of the several trials evaluating the combination of Keytruda plus Lynparza. In addition to metastatic prostate cancer, this combination is also being studied in advanced lung cancer, ovarian cancer, and triple-negative breast cancer, as well as across solid tumours with certain biomarkers, mentioned the statement.