On May 5, 2021, the U.S. Food and Drug Administration (FDA) granted accelerated approval to pembrolizumab (Keytruda®) in combination with trastuzumab and fluoropyrimidine- and platinum-containing chemotherapy for first-line treatment of patients with locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma.

FDA Grants Accelerated Approval to Pembrolizumab for HER2-Positive Gastric Cancer

Approval was based on the prespecified interim analysis of the first 264 participants in an ongoing multicenter, randomized, doubleblind, placebocontrolled trial (KEYNOTE-811; NCT03615326) of patients with HER2positive advanced gastric or GEJ adenocarcinoma who had not previously received systemic therapy for metastatic disease. Patients were randomized 1:1 to receive pembrolizumab 200 mg or placebo every three weeks in combination with trastuzumab and either fluorouracil plus cisplatin or capecitabine plus oxaliplatin.

The main efficacy measure was overall response rate (ORR) assessed by blinded independent review committee. ORR was 74% (95% CI = 66, 82) in the pembrolizumab arm and 52% (95% CI = 43, 61) in the placebo arm (one-sided p-value< 0.0001, statistically significant). The median duration of response (DoR) was 10.6 months (range = 1.1+, 16.5+) for patients treated with pembrolizumab and 9.5 months (range = 1.4+, 15.4+) for those in the placebo arm. 

The adverse reaction profile observed in patients receiving pembrolizumab was consistent with the known pembrolizumab safety profile.

The recommended pembrolizumab dose for adult patients with locally advanced unresectable or metastatic HER2-positive gastric or GEJ adenocarcinoma in combination with trastuzumab and chemotherapy is 200 mg every three weeks or 400 mg every six weeks.

View the full prescribing information for pembrolizumab.

The review used the Real Time Oncology Review pilot program, which streamlined data submission prior to the filing of the entire clinical application, and Assessment Aid, a voluntary submission from the applicant to facilitate FDA’s assessment.

FDA granted the application priority review. A description of FDA expedited programs is in the Guidance for Industry—Expedited Programs for Serious Conditions—Drugs and Biologics

Healthcare professionals should report all serious adverse events they suspect are associated with the use of any medicine or device to FDA’s MedWatch Reporting System or by calling 800-FDA-1088.  

For assistance with single-patient oncology investigational new drug applications, contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov