Merck provided updates on two Phase 3 trials, KEYNOTE-641 and KEYNOTE-789. Merck is discontinuing the Phase 3 KEYNOTE-641 trial evaluating KEYTRUDA® (pembrolizumab), Merck's anti-PD-1 therapy, in combination with enzalutamide and androgen deprivation therapy (ADT) for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) based on the recommendation of an independent Data Monitoring Committee. At an interim analysis, KEYTRUDA in combination with enzalutamide and ADT did not demonstrate an improvement in radiographic progression-free survival (rPFS) or overall survival (OS), the trial's dual primary endpoints, compared to placebo plus enzalutamide and ADT, and crossed a pre-specified futility boundary for OS.

Merck is informing study investigators of the decision and advises patients in the study to speak to their physician regarding treatment. Merck also announced that the Phase 3 KEYNOTE-789 trial evaluating KEYTRUDA in combination with pemetrexed plus platinum-based chemotherapy did not meet its dual primary endpoint of OS for the treatment of patients with metastatic nonsquamous non-small cell lung cancer (NSCLC), with epidermal growth factor receptor (EGFR)-genomic tumor mutations, who have previously progressed on a tyrosine kinase inhibitor (TKI), including osimertinib. At the final analysis of the study, there was an improvement in OS for patients who received KEYTRUDA plus pemetrexed with platinum-based chemotherapy compared to pemetrexed with platinum-based chemotherapy; however, these results did not meet statistical significance per the pre-specified statistical plan.

At an earlier interim analysis, the trial's other dual primary endpoint, progression-free survival (PFS) was tested and showed an improvement in the KEYTRUDA arm compared to chemotherapy alone, but these results did not reach statistical significance. In KEYNOTE-641 and KEYNOTE-789, the safety profile of KEYTRUDA was consistent with that observed in previously reported studies and no new safety signals were identified. In KEYNOTE-641, the combination was associated with a higher incidence of Grade 3-5 adverse events and serious adverse events compared to the control arm.

Results will be shared at future scientific congresses. KEYNOTE-641 is a randomized, double-blind Phase 3 trial evaluating KEYTRUDA in combination with enzalutamide and ADT versus placebo in combination with enzalutamide and ADT in patients with mCRPC who have not received chemotherapy for mCRPC, are abiraterone-naïve or are intolerant to or progressed on abiraterone acetate. The primary endpoints are OS and rPFS per Prostate Cancer Working Group-modified RECIST v1.1 as assessed by blinded independent central review.

Secondary endpoints include objective response rate (ORR), duration of response (DOR) and safety. The trial enrolled an estimated 1,240 patients who were randomized to receive KEYTRUDA (200 mg intravenously every three weeks for up to two years) plus enzalutamide (160 mg daily) or placebo plus enzalutamide. KEYNOTE-789 is a randomized, double-blind Phase 3 trial investigating KEYTRUDA with pemetrexed plus platinum-based chemotherapy compared with pemetrexed plus platinum-based chemotherapy for the treatment of patients with TKI-resistant, EGFR-mutated metastatic, nonsquamous NSCLC.

These patients experienced disease progression per RECIST v1.1 criteria following treatment with TKI therapy and either had: a) T790M-negative mutation tumors; b) T790M-positive mutation tumors with prior exposure to osimertinib; or c) first-line osimertinib failure regardless of T790M mutation status. The primary endpoints are OS and PFS. Secondary endpoints include ORR, DOR and safety.

The study enrolled 492 patients who were randomized to receive either: KEYTRUDA (200 mg intravenously [IV] on Day 1 of each three-week cycle for up to 35 cycles) plus pemetrexed (500 mg/m2 by IV every three weeks with no restrictions on the number of cycles) plus platinum chemotherapy (either carboplatin [Area Under the Curve [AUC] 5 by IV every three weeks for four cycles] or cisplatin [75 mg/m2 by IV every three weeks for four cycles]); or Placebo (saline by IV on Day 1 of each three-week cycle for up to 35 cycles) plus pemetrexed (500 mg/m2 by IV every three weeks with no restrictions on the number of cycles) plus platinum chemotherapy (either carboplatin [AUC 5 by IV every three weeks for four cycles] or cisplatin.