FDA granted traditional approval to Keytruda for HER2+PD-L1+ gastric or GEJ adenocarcinoma
On Mar. 19, 2025, FDA approved pembrolizumab (Keytruda, Merck) + trastuzumab + chemotherapy for 1L treatment of adult locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma expressing PD-L1 (CPS ≥1).
Pembrolizumab previously received accelerated approval for this indication on May 5, 2021 based on interim analysis of the same trial.
KEYNOTE-811 trial (NCT03615326): Randomized, double-blind, placebo-controlled trial in 698 patients not previously treated with systemic therapy for metastatic disease. 85% of the 698 patients' tumors expressed PD-L1 (CPS ≥1 with PD-L1 IHC 22C3 pharmDx kit).
Efficacy:
Progression-free survival (PFS) and overall survival (OS) were primary endpoints. Overall response rate (ORR) and duration of response (DOR) were secondary endpoints.
In patients with PD-L1 CPS≥1 tumors,
- Median PFS was 10.9 months in pembro + trastuzumab + chemo arm versus 7.3 months in placebo + trastuzumab + chemo arm (Hazard ratio [HR] 0.72 [95% CI: 0.60, 0.87]).
- Median OS was 20.1 months for pembrolizumab arm compared to 15.7 months for placebo (HR 0.79 [95% CI: 0.66, 0.95]).
- ORR was 73% (95% CI: 68, 78) versus 58% (95% CI: 53, 64) for the respective groups.
- Median DOR was 11.3 months (95% CI: 9.9, 13.7) versus 9.6 months (95% CI: 7.1, 11.2).
Safety: The adverse reaction profile was consistent with known safety profile.
Regulatory Review:
- Assessment Aid
- Orphan Drug Designation
- Project FrontRunner (support earlier treatment options for advanced disease)