Phase 3 KEYNOTE-590 Trial of Pembrolizumab Plus Chemo Meets Primary End Points of OS, PFS

The pivotal phase 3 KEYNOTE-590 trial evaluating pembrolizumab (Keytruda) in combination with cisplatin plus 5-fluorouracil (chemotherapy) met its dual primary end points of overall survival (OS) and progression-free survival (PFS) for the first-line treatment of patients with locally advanced or metastatic esophageal cancer, according to Merck, the developer of the agent.

According to an interim analysis conducted by an independent Data Monitoring Committee, pembrolizumab in combination with chemotherapy showed a statistically significant and clinically meaningful improvement in OS and PFS compared with chemotherapy, the current standard of care, in the intention-to-treat (ITT) population.

The study also met the key secondary end point of objective response rate (ORR), with significant improvements observed with pembrolizumab in combination with chemotherapy compared with chemotherapy alone. Other key secondary end points for the study include duration of response and safety.

Results from the trial will be shared with global regulatory authorities and have already 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,” Roy Baynes, MD, PhD, senior vice president and head of Global Clinical Development as well as chief medical officer at Merck Research Laboratories, said in a press release. “In this pivotal study, [pembrolizumab] 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 [pembrolizumab], and we look forward to engaging regulatory authorities as quickly as possible.”

The randomized, double-blind, phase 3 trial enrolled 749 patients. Participants were randomized to receive either:

• 200 mg of pembrolizumab intravenously (IV) on day 1 of each 3-week cycle for up to 35 cycles; plus 80 mg/m2 of cisplatin by IV on day 1 of each 3-week cycle for up to 6 cycles; plus 800 mg/m2 of 5-fluorocil by IV per day on day 1 to day 5 of each 3-week cycle, or per local standard for 5-fluorocil administration, for up to 35 cycles.
• Placebo; plus 80 mg/m2 of cisplatin by IV on day 1 of each 3-week cycle for up to 6 cycles; plus 800 mg/m2 of 5-fluorocil by IV per day on day 1 to day 5 of each 3-week cycle, or per local standard for 5-fluorocil administration, for up to 35 cycles.

Notably, the safety profile of pembrolizumab in this trial was found to be consistent with that observed in previously reported studies.

Currently, pembrolizumab is 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 also indicated it is continuing to study pembrolizumab across multiple settings and stages of gastrointestinal cancer, including gastric, hepatobiliary, esophageal, pancreatic, colorectal and anal cancers, through its broad clinical program.

Reference:

Merck’s KEYTRUDA® (pembrolizumab) in Combination With Chemotherapy Significantly Improved Overall Survival and Progression-Free Survival Compared With Chemotherapy in Locally Advanced or First-Line Metastatic Esophageal Cancer [news release]. Kenilworth, NJ. Published August 19, 2020. Accessed August 19, 2020. https://www.merck.com/news/mercks-keytruda-pembrolizumab-in-combination-with-chemotherapy-significantly-improved-overall-survival-and-progression-free-survival-compared-with-chemotherapy-in-locally-advanced-or/