FDA Approves Keytruda Combo Therapy

The full approval was supported by data from the phase III KEYNOTE-811 trial (NCT03615326), which showed that in patients with a PD-L1 CPS of at least 1, the median progression-free survival (PFS) was 10.9 months (95% CI, 8.5-12.5) in the pembrolizumab arm (n = 298) vs 7.3 months (95% CI, 6.8-8.4) in the placebo arm (n = 296; HR, 0.72; 95% CI, 0.60-0.87). Data from the final analysis of the study presented at the  2024 ESMO conference showed that in the population of patients with a PD-L1 CPS of at least 1, the median overall survival (OS) was 20.1 months (95% CI, 17.9-22.9) in the pembrolizumab arm vs 15.7 months (95% CI, 13.5-18.5) in the placebo arm (HR, 0.79; 95% CI, 0.66-0.95).  

The combination received accelerated  approval for use in patients with locally advanced unresectable or metastatic HER2- positive/GEJ cancer regardless of PD-L1 expression. The FDA amended the accelerated approval in November 2023 to limit the combination’s use to patients with a PD-L1 CPS of 1 or more as determined by a FDA approved test.

KEYNOTE-811 is a randomized, double-blind Phase III trial (ClinicalTrials.gov, NCT03615326 ) evaluating Keytruda in combination with trastuzumab and chemotherapy for the first-line treatment of locally advanced unresectable or metastatic HER2-positive gastric or GEJ adenocarcinoma. The dual primary endpoints are PFS per RECIST v1.1 as assessed by blinded independent central review and OS. Secondary endpoints include objective response rate (ORR), duration of response and safety. The trial enrolled 698 patients who were randomized to receive Keytruda (200 mg every three weeks) in combination with trastuzumab, fluoropyrimidine- and platinum-containing chemotherapy (investigator’s choice of 5-fluorouracil plus cisplatin or capecitabine plus oxaliplatin), or placebo in combination with trastuzumab and chemotherapy.