US - FDA Approves Keytruda (pembrolizumab) Plus Chemo for HER2-Negative Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma

On Nov. 16, 2023, US FDA approved pembrolizumab (Keytruda) with chemotherapy for 1L locally advanced unresectable or metastatic HER2-negative (HER2-) gastric or gastroesophageal junction (GEJ) adenocarcinoma.

·       This review used Project Orbis. FDA collaborated with the Australian Therapeutic Goods Administration (TGA), Health Canada, and Switzerland’s Swissmedic. The application reviews are ongoing at the other regulatory agencies.

·       This application was granted Orphan Drug Designation. Assessment Aid, a voluntary submission from the applicant, was used to facilitate FDA review.

KEYNOTE-859 (NCT03675737) is a randomized, double-blind, placebo-controlled multicenter Phase 3 trial (n = 1579) in HER2- advanced gastric or GEJ adenocarcinoma patients who had not previously received systemic therapy for metastatic disease.

Primary efficacy endpoint was overall survival (OS). Secondary efficacy outcome measures included progression free survival (PFS), overall response rate (ORR), and duration of response (DOR) as assessed by blinded independent central review (BICR) according to RECIST v1.1.

Treatment with pembrolizumab and chemotherapy resulted in a statistically significant improvement in OS, PFS, and ORR.

Median OS was 12.9 months (95% CI: 11.9, 14.0) in the pembrolizumab arm compared to 11.5 months (95% CI: 10.6, 12.1) in the placebo arm (hazard ratio [HR] 0.78 [95% CI: 0.70, 0.87]).

Median PFS was 6.9 months (95% CI: 6.3, 7.2) and 5.6 months (95% CI: 5.5, 5.7) (HR 0.76 [95% CI: 0.67, 0.85]) in the respective arms.

ORR was 51% (95% CI: 48, 55) and 42% (95% CI: 38, 45) in the respective arms; median DOR was 8 months (95% CI: 7.0, 9.7) in the pembrolizumab arm and 5.7 months (95% CI: 5.5, 6.9) in the placebo arm.

Serious adverse reactions occurred in 45% of patients receiving pembrolizumab. Permanent discontinuation of pembrolizumab due to adverse reactions occurred in 15% of patients. Adverse reactions resulting in permanent discontinuation in ≥1% were infections and diarrhea.

Link to FDA announcement

Link to Merck press release