Merck’s Keytruda receives Japanese approval to treat patients with radically unresectable urothelial carcinoma

Kenilworth, New JerseyWednesday, January 3, 2018, 14:00 Hrs  [IST]

Merck, known as MSD outside the United States and Canada, announced that Keytruda (pembrolizumab), the company’s anti-PD-1 therapy, has been approved by the Japanese Ministry of Health, Labor and Welfare (MHLW) for the treatment of patients with radically unresectable urothelial carcinoma who progressed after cancer chemotherapy. The approval is based on data from the phase 3 KEYNOTE-045 trial, which demonstrated superior overall survival (OS) for Keytruda versus investigator-choice chemotherapy (paclitaxel, docetaxel, vinflunine) (HR, 0.73 [95% CI, 0.59, 0.91], p=0.002).

“Chemotherapy has long been the standard of care for advanced urothelial carcinoma, with few options available for patients whose disease progresses,” said Dr. Roy Baynes, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories. “We welcome the approval of Keytruda as the first anti-PD-1 therapy for these patients in Japan based on the compelling overall survival data from KEYNOTE-045.”

With this approval, Keytruda is now indicated for use in four types of cancer in Japan, including for the treatment of radically unresectable melanoma, PD-L1-positive unresectable advanced or recurrent non-small cell lung cancer and relapsed or refractory classical Hodgkin lymphoma. MSD will market Keytruda in Japan and will promote it with Taiho Pharmaceutical Co., Ltd.

KEYNOTE-045 is a multicenter, randomized, controlled phase 3 trial investigating Keytruda (pembrolizumab) in patients with locally advanced or metastatic urothelial carcinoma with disease progression on or after platinum-containing chemotherapy. Patients were randomized (1:1) to receive either Keytruda 200 mg every three weeks (n=270) or investigator’s choice of any of the following chemotherapy regimens, all given intravenously every three weeks (n=272): paclitaxel 175 mg/m2, docetaxel 75 mg/m2, or vinflunine 320 mg/m2. The primary efficacy outcomes were OS and progression-free survival (PFS) (as assessed by BICR using RECIST v1.1); secondary outcome measures were objective response rate (ORR) (as assessed by BICR using RECIST v1.1) and duration of response.

In the study, Keytruda demonstrated a statistically significant improvement in OS compared to chemotherapy. Findings demonstrated that Keytruda resulted in a 27 percent reduction in the risk of death compared to chemotherapy (HR, 0.73 [95% CI, 0.59, 0.91], p=0.002); the median OS was 10.3 months with Keytruda (95% CI, 8.0-11.8) and 7.4 months with chemotherapy (95% CI, 6.1-8.3). There was no statistically significant difference between Keytruda and chemotherapy with respect to PFS (HR, 0.98 [95% CI, 0.81-1.19], p=0.416). The median PFS was 2.1 months with Keytruda (95% CI, 2.0-2.2) and 3.3 months with chemotherapy (95% CI, 2.3-3.5).

The Japanese package insert notes that, in KEYNOTE-045, adverse reactions were observed in 162 (60.9%) of 266 patients treated with Keytruda in the safety analysis (including 16 of 30 Japanese patients). The most commonly observed adverse reactions (=10%) were pruritus in 52 patients (19.5%), fatigue in 37 patients (13.9%) and nausea in 29 patients (10.9%).

Keytruda is an anti-PD-1 therapy that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. Keytruda is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.

Merck has the industry’s largest immuno-oncology clinical research program, which currently involves more than 650 trials studying Keytruda across a wide variety of cancers and treatment settings. The Keytruda clinical program seeks to understand the role of Keytruda across cancers and the factors that may predict a patient’s likelihood of benefitting from treatment with Keytruda, including exploring several different biomarkers.