With More than One-Year Follow-Up, Merck & Co.’s KEYTRUDA (Pembrolizumab) Shows Continued Overall Survival Benefit Over Chemotherapy As Second-Line Treatment For Advanced Urothelial Carcinoma Patients Post-Platinum Failure

Findings to Be Presented at 2017 ASCO Annual Meeting Also Include Updated Data Evaluating Duration of Response in Previously Untreated (First-Line) Urothelial Carcinoma Patients Ineligible for Cisplatin-Based Therapy

KENILWORTH, N.J.--(BUSINESS WIRE)--Merck (NYSE:MRK), known as MSD outside the United States and Canada, today announced updated results from KEYNOTE-045 and KEYNOTE-052, two studies investigating KEYTRUDA^® (pembrolizumab), the company’s anti-PD-1 therapy, in certain patients with locally advanced or metastatic urothelial carcinoma, a type of bladder cancer. These data – which include updated survival and biomarker analyses – demonstrate the clinical benefit of KEYTRUDA as a second-line therapy for patients post-platinum failure and as a first-line treatment for patients ineligible for cisplatin-based therapy. Specifically, in the second-line setting, KEYTRUDA improved overall survival (OS) compared to chemotherapy – reducing the risk of death by 30 percent (HR, 0.70 [95% CI, 0.57-0.86], p = 0.0004) – and, in the first-line setting, KEYTRUDA demonstrated an overall response rate (ORR) of 29 percent (95% CI, 25-34). Findings will be presented in two oral sessions at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago on Monday, June 5, from 8:12 to 8:36 a.m. CDT (Location: Arie Crown Theater) (Abstracts #4501 and #4502).

“Historically, there have been limited treatment options for patients with advanced urothelial bladder cancer,” said Dean F. Bajorin, M.D., medical oncologist at Memorial Sloan Kettering Cancer Center. “For patients with this devastating disease, the efficacy and safety profile we have observed with KEYTRUDA in these treatment settings represent an important new option.”

“The updated data at ASCO in previously treated urothelial cancer patients continue to support the overall survival benefit we have observed in the second-line treatment setting and the response rates demonstrated in cisplatin-ineligible patients,” said Dr. Roger Dansey, senior vice president and therapeutic area head, oncology late-stage development, Merck Research Laboratories. “Beyond these two studies, we are studying KEYTRUDA in other treatment settings and look forward to executing on our robust clinical development program in bladder cancer."

The KEYTRUDA (pembrolizumab) clinical development program includes more than 30 tumor types in more than 500 clinical trials, including more than 300 trials that combine KEYTRUDA with other cancer treatments. Currently, Merck has the largest immuno-oncology clinical development program in bladder cancer, with 29 trials underway involving KEYTRUDA as monotherapy and in combination, including four registration-enabling studies.

Data in Second-Line Post-Platinum Failure Patients, KEYNOTE-045 (Abstract #4501)

KEYNOTE-045 is a multicenter, randomized, active-controlled, phase 3 trial, investigating KEYTRUDA in 542 patients with locally advanced or metastatic urothelial carcinoma with disease progression on or after platinum-containing chemotherapy (additional details on the trial design are provided below). Data to be presented at ASCO are based on longer follow-up (median follow-up of 18.5 months as of Jan. 18, 2017; range: 14.2-26.5), which continues to show a superior OS advantage with KEYTRUDA compared to chemotherapy in the second-line treatment of patients with advanced urothelial carcinoma who have progressed during or following platinum-containing chemotherapy, regardless of PD-L1 expression.

Analyses of the primary endpoints showed a 30 percent reduction in the risk of death with KEYTRUDA (n=270) compared to chemotherapy (n=272) (HR, 0.70 [95% CI, 0.57-0.86], p = 0.0004). The median OS with KEYTRUDA was 10.3 months (95% CI, 8.0-12.3) versus 7.4 months with chemotherapy (95% CI, 6.1-8.1). As previously reported, there was no significant improvement in progression-free survival (PFS) between arms (HR, 0.96 [95% CI, 0.79-1.16], p= 0.32). The median PFS was 2.1 months (95% CI, 2.0-2.2) in the KEYTRUDA arm and 3.3 months (95% CI, 2.4-3.5) in the chemotherapy arm. The six-month, 12-month and 18-month PFS rates in the KEYTRUDA arm were 28.8 percent, 17.6 percent and 16.8 percent, respectively; the six-month, 12-month and 18-month PFS rates in the chemotherapy arm were 28.4 percent, 7.9 percent and 3.5 percent, respectively.

Analyses of the secondary endpoints showed a higher ORR with KEYTRUDA compared to chemotherapy. In patients treated with KEYTRUDA, the ORR was 21.1 percent – with a complete response rate of 7.8 percent and a partial response rate of 13.3 percent. In patients treated with chemotherapy, the ORR was 11.0 percent – with a complete response rate of 2.9 percent and a partial response rate of 8.1 percent. The median duration of response had not been reached in the KEYTRUDA (pembrolizumab) arm (range: 1.6+-20.7+) and was 4.4 months in the chemotherapy arm (range: 1.4+-20.3+).

The safety profile of KEYTRUDA was consistent with that observed in previously reported studies. Grade 1-2 treatment-related adverse events in the KEYTRUDA arm included anemia, asthenia, constipation, decreased appetite, diarrhea, fatigue, nausea, peripheral neuropathy, peripheral sensory neuropathy and pruritus. Grade 3-5 treatment-related adverse events in the KEYTRUDA arm included anemia, asthenia, decreased neutrophils, diarrhea, fatigue, nausea and pruritus. Grade 3-5 immune-mediated adverse events included adrenal insufficiency, colitis, nephritis, pneumonitis and severe skin reaction.