On October 8, 2016 Merck (NYSE:MRK), known as MSD outside the United States and Canada, reported positive findings from the phase 2 KEYNOTE-052 study investigating the use of KEYTRUDA (pembrolizumab), the company’s anti-PD-1 therapy, in previously untreated patients with unresectable (inoperable) or metastatic urothelial cancer who are ineligible for cisplatin-based therapy. Data presented at the ESMO (Free ESMO Whitepaper) 2016 Congress, the annual meeting of the European Society for Medical Oncology, showed an overall response rate (ORR) of 24 percent (n=24/100) (95% CI, 16-34) in the total study population, which included patients with and without PD-L1 expression.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We have a growing body of evidence of KEYTRUDA’s activity in a range of cancers and treatment settings including the first-line treatment of patients with advanced urothelial cancer who will not tolerate cisplatin-based therapy," said Dr. Roger Dansey, senior vice president, oncology late-stage development, Merck Research Laboratories.

The KEYTRUDA clinical development program includes more than 30 tumor types in more than 350 clinical studies, including more than 100 trials that combine KEYTRUDA with other cancer treatments. Merck has the largest immuno-oncology clinical development program in bladder cancer with 27 trials involving KEYTRUDA, including four registration-enabling studies currently underway.

"There have been very few advancements in the treatment of bladder cancer in the past several decades, and patients with urothelial cancer who are ineligible for cisplatin-based therapy are in significant need of new approaches to care," said Dr. Dean F. Bajorin, study investigator and medical oncologist at Memorial Sloan Kettering Cancer Center. "These data are exciting and demonstrate the potential for an anti-PD-1 therapy, such as pembrolizumab, to address the unmet treatment need that exists today for cisplatin-ineligible patients with this type of urothelial cancer."

Findings from KEYNOTE-052 are being presented at the ESMO (Free ESMO Whitepaper) 2016 Congress by Dr. Arjun V. Balar, medical oncologist and assistant professor of medicine at the Perlmutter Cancer Center at NYU Langone Medical Center, on Oct. 8 from 9:30 – 9:45 a.m. CEST (Abstract: # LBA32_PR) and are featured in the official ESMO (Free ESMO Whitepaper) press program.

Additional Findings from KEYNOTE-052

KEYNOTE-052 is an open-label, phase 2 study evaluating KEYTRUDA (pembrolizumab) (200 mg every three weeks) monotherapy as a first-line treatment in an estimated 350 patients with unresectable (inoperable) or metastatic urothelial cancer (a type of bladder cancer) who are ineligible for cisplatin-based therapy. The primary endpoints include ORR in all patients enrolled in the study (total study population) and in patients with PD-L1 positive tumors (expression of one percent or more). Secondary endpoints include duration of response, progression-free survival (PFS), and overall survival (OS). Tumor response was measured according to RECIST (Response Evaluation Criteria in Solid Tumors) v1.1 as assessed by blinded independent central review.

Findings presented at the ESMO (Free ESMO Whitepaper) 2016 Congress are from the planned interim analysis of the first 100 patients, which was intended to evaluate ORR and determine the PD-L1-high expression cut-point as examined by expression in tumor and immune cells. Forty-five percent of patients (n=45/100) had an ECOG (Eastern Cooperative Oncology Group) Performance Status (PS) score of two, 30 percent (n=30/100) had a PS score of one, and 24 percent (n=24/100) had a PS score of zero.

In the total study population, ORR was 24 percent (n=24/100) (95% CI, 16-34) with a complete response rate of six percent (n=6/100) (95% CI, 2-13). Review of the outcomes based on PD-L1 expression showed that in patients with PD-L1 expression of less than one percent, ORR was 18 percent (n=6/33) (95% CI, 7-36) with a complete response rate of three percent (n=1/33) (95% CI, 0.1-16); in patients with PD-L1 expression greater than or equal to one percent and less than 10 percent, ORR was 15 percent (n=5/33) (95% CI, 5-32) with no complete responses; and, in patients expressing PD-L1 at levels equal to or greater than 10 percent, ORR was 37 percent (n=11/30) (95% CI, 20-56) with a complete response rate of 13 percent (n=4/30) (95% CI, 4-31). Among the 24 percent of patients in the total study population who were responding to treatment, the median duration of response had not been reached (range 1.4+ to 9.8+ months), with 83 percent of patients (n=20/24) having responses of six months or longer.

The safety profile of KEYTRUDA (pembrolizumab) was consistent with that observed in previously reported KEYTRUDA studies. The treatment-related adverse events observed in this trial (any grade occurring in five percent or more of patients) were fatigue (n=14), pruritus (n=12), pyrexia (n=8), decreased appetite (n=7), diarrhea (n=7), rash (n=7), chills (n=6), hypothyroidism (n=6), and nausea (n=6). Grade 3-4 treatment-related adverse events observed (occurring in 2 or more patients) were fatigue (n=4), muscle spasms (n=2), decreased appetite (n=1), and diarrhea (n=1). Immune-mediated adverse events of Grade 3-4 were nephritis (n=1) and pneumonitis (n=2). Five patients discontinued due to a treatment-related adverse event; there were no treatment-related deaths.