Background
Phase III, N=643 (pembro+paclitaxel n=322, placebo+paclitaxel n=321), platinum-resistant recurrent ovarian cancer, 1-2 prior systemic regimens, multicentre 187 sites in 25 countries, median follow-up ~24 months at final analysis
Interventions and follow up
Arm A: Pembrolizumab 400 mg IV q6 weeks + weekly paclitaxel 80 mg/m² days 1,8,15 q21d (± bevacizumab per protocol)
Arm B: Placebo IV q6 weeks + weekly paclitaxel 80 mg/m² days 1,8,15 q21d (± bevacizumab per protocol)
Primary endpoint: Progression-free survival (investigator-assessed RECIST 1.1); key secondary: overall survival
mFollow up: ~24 months for final OS analysi
Arm B: Placebo IV q6 weeks + weekly paclitaxel 80 mg/m² days 1,8,15 q21d (± bevacizumab per protocol)
Primary endpoint: Progression-free survival (investigator-assessed RECIST 1.1); key secondary: overall survival
mFollow up: ~24 months for final OS analysi
Results
PFS (first interim): Pembrolizumab+paclitaxel median 8.3 months vs placebo 6.4 months (overall population), HR 0.70 [95% CI 0.58-0.84], P<.0001
OS (second interim): Median 17.7 months (pembro) vs 14.0 months (placebo), HR 0.82 [95% CI 0.69-0.97], P=.011
OS (second interim): Median 17.7 months (pembro) vs 14.0 months (placebo), HR 0.82 [95% CI 0.69-0.97], P=.011
Adverse events
Main adverse events: Grade 3+ AE: 68% (pembrolizumab+paclitaxel) vs 55% (placebo+paclitaxel). Anemia, peripheral neuropathy, alopecia, fatigue, nausea most common. Treatment-related deaths: 4 (1%) vs 5 (2%), including colitis and ILD.
Conclusions
Pembrolizumab plus weekly paclitaxel with or without bevacizumab significantly improves PFS and OS in platinum-resistant recurrent ovarian cancer. New treatment option for 1-2 prior regimens; PD-L1 CPS ≥1 enrichment shows enhanced benefit.
Key Limitations
Key Limitations: Modest OS gain (~4 months) with 13% increase in Grade 3+ AE. Heterogeneous patient population (bevacizumab-permissive design). PD-L1 stratification shows unequal benefit CPS 0 vs ≥1; overall population benefit narrower.
Clinical Context
ENGOT-ov65/KEYNOTE-B96 validates IO+chemotherapy in platinum-resistant ovarian setting. Complements ROSELLA (GR antagonist) and bevacizumab strategies. Establishes pembrolizumab as option for early recurrence (≤6 months platinum).
References
References: Colombro N et al, Lancet, 2026