Date: 20-Aug-2020

Mercks Phase 3 KEYNOTE-590 Trial Of Keytruda In Combo With Chemotherapy Meets Primary Endpoints Of OS And PFS To Treat Locally Advanced Or Metastatic

Merck, known as MSD outside the United States and Canada, announced that the pivotal phase 3 KEYNOTE-590 trial evaluating Keytruda, Merck’s anti-PD-1 therapy, in combination with chemotherapy (cisplatin plus 5-fluorouracil [5-FU]), met its primary endpoints of overall survival (OS) and progression-free survival (PFS) for the first-line treatment of patients with locally advanced or metastatic esophageal cancer.

Based on an interim analysis conducted by an independent Data Monitoring Committee, Keytruda in combination with chemotherapy demonstrated a statistically significant and clinically meaningful improvement in OS and PFS compared with chemotherapy (cisplatin plus 5-FU), the current standard of care, in the intention-to-treat (ITT) population. The study also met the key secondary endpoint of objective response rate (ORR), with significant improvements for Keytruda in combination with chemotherapy compared with chemotherapy alone. The safety profile of Keytruda in this trial was consistent with that observed in previously reported studies. Results will be shared with global regulatory authorities and have been submitted for presentation at the European Society for Medical Oncology (ESMO) Virtual Congress 2020.

“Esophageal cancer is a devastating malignancy with a high mortality rate and few treatment options in the first-line setting beyond chemotherapy,” said Dr. Roy Baynes, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories. “In this pivotal study, Keytruda plus chemotherapy resulted in superior overall survival compared with the current standard of care in the full study population and across all patient groups evaluated. These results build upon our research reinforcing the survival benefits of Keytruda, and we look forward to engaging regulatory authorities as quickly as possible.”

Keytruda is currently approved in the US and China as monotherapy for the second-line treatment of patients with recurrent locally advanced or metastatic squamous cell carcinoma of the esophagus whose tumors express PD-L1 (Combined Positive Score [CPS] =10). Merck is continuing to study Keytruda across multiple settings and stages of gastrointestinal cancer – including gastric, hepatobiliary, esophageal, pancreatic, colorectal and anal cancers – through its broad clinical programme.

KEYNOTE-590 is a randomized, double-blind, phase 3 trial (ClinicalTrials.gov, NCT03189719) evaluating Keytruda in combination with chemotherapy compared with placebo plus chemotherapy for the first-line treatment of patients with locally advanced or metastatic esophageal carcinoma (adenocarcinoma or squamous cell carcinoma of the esophagus or Siewert type 1 adenocarcinoma of the esophagogastric junction). The primary endpoints are OS and PFS. The secondary endpoints include ORR, duration of response and safety. The study enrolled 749 patients who were randomized to receive:

Keytruda (200 mg intravenously [IV] on Day 1 of each three-week cycle for up to 35 cycles); plus cisplatin (80 mg/m2 IV on Day 1 of each three-week cycle for up to six cycles); plus 5-FU (800 mg/m2 IV per day on Day 1 to Day 5 of each three-week cycle, or per local standard for 5-FU administration, for up to 35 cycles); or Placebo; plus cisplatin (80 mg/m2 IV on Day 1 of each three-week cycle for up to six cycles); plus 5-FU (800 mg/m2 IV per day on Day 1 to Day 5 of each three-week cycle, or per local standard for 5-FU administration, for up to 35 cycles).

Esophageal cancer, a type of cancer that is particularly difficult to treat, begins in the inner layer (mucosa) of the esophagus and grows outward. The two main types of esophageal cancer are squamous cell carcinoma and adenocarcinoma. Esophageal cancer is the seventh most commonly diagnosed cancer and the sixth leading cause of death from cancer worldwide. Globally, it is estimated there were more than 572,000 new cases of esophageal cancer diagnosed and nearly 509,000 deaths resulting from the disease in 2018. In the US alone, it is estimated there will be nearly 18,500 new cases of esophageal cancer diagnosed and more than 16,000 deaths resulting from the disease in 2020.

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. There are currently more than 1,200 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.

Keytruda is indicated for the treatment of patients with unresectable or metastatic melanoma.

Keytruda is indicated for the adjuvant treatment of patients with melanoma with involvement of lymph node(s) following complete resection.