The U.S. Food and Drug Administration (FDA) has accepted for review the supplemental Biologics Licence Application (sBLA) seeking approval for Keytruda (pembrolizumab) to treat patients with recurrent or advanced gastric or gastroesophageal junction adenocarcinoma who have received at least two prior lines of chemotherapy.
The sBLA was granted priority review, which reduces the review time from 10 months to six months. The FDA set an action date for Sept. 22, 2017.
“An estimated nearly [100,000] people are living with gastric cancer in the U.S., yet little progress has been made in bringing forward new treatment options to these patients for whom chemotherapy has long been the standard of care,” Dr. Roger Dansey, senior vice president and therapeutic area head of oncology late-stage development at Merck Research Laboratories, said in a news release.
“We look forward to working with the FDA to bring Keytruda to people with gastric cancer who have progressed after receiving chemotherapy and are in urgent need of another option,” he said.
The application is based on data from cohort one (of three cohorts) of the KEYNOTE-059 Phase 2 trial (NCT02335411) assessing the safety and effectiveness of Keytruda in heavily treated patients with recurrent or advanced gastric (stomach) or gastroesophageal junction adenocarcinoma, whose disease progressed after two or more lines of chemotherapy.
In this cohort, 259 patients received Keytruda monotherapy at a fixed dose of 200 mg every three weeks for up to 24 months. About half of these patients were receiving Keytruda as a third-line therapy. The other half received it as a fourth-line or higher therapy.
The study’s primary outcomes were the number of participants experiencing adverse events, patients who discontinued Keytruda due to adverse events, and the objective response rate.
Data from this cohort, to be presented at the American Society of Clinical Oncology (ASCO) 2017 Annual Meeting June 2-6 in Chicago, revealed that 11.2% of patients responded to Keytruda monotherapy, including 1.9% who showed a complete response, with a median duration of response of 8.1 months. Also, 17% of patients had stable disease.
Patients receiving Keytruda as a third-line therapy had better response rates than those who received it as a fourth-line or higher treatment (14.9% vs. 7.2%). Similarly, more patients whose tumors were positive for PD-L1 responded to treatment, compared to those who were negative for PD-L1 (15.5% vs. 5.5%).
As a result, PD-L1-positive patients receiving Keytruda as a third-line therapy had the best overall response rates — 21.3%, with 4% showing complete responses.
Forty-three patients (16.6%) experienced Grade 3-5 treatment-related adverse events. Two patients discontinued treatment due to liver-related complications and two patients died, one with acute kidney injury and the other with pleural effusion.
Two other cohorts in the Keynote-059 trial had not been previously treated for their cancer. One cohort received Keytruda as a monotherapy, and the other as a combination therapy.
The oral session is at 9 a.m. June 4 and is titled, “KEYNOTE-059 cohort 1: Efficacy and safety of pembrolizumab (pembro) monotherapy in patients with previously treated advanced gastric cancer.”