Pembrolizumab/Chemotherapy Improves Survival in Recurrent PROC

Previously, the KEYNOTE-B96 trial met its primary end point of progression-free survival in PD-L1–expressing platinum-resistant recurrent ovarian cancer, as well as for all comers.

Pembrolizumab (Keytruda) in combination with chemotherapy with or without bevacizumab (Avastin) exhibited an overall survival (OS) benefit vs placebo and chemotherapy among an all-comers population of patients with platinum-resistant recurrent ovarian cancer, meeting the secondary end point of OS in the phase 3 KEYNOTE-B96/ENGOT-ov65 trial (NCT05116189), according to a news release from the drug’s developer, Merck.1

Previously, the KEYNOTE-B96 trial met its primary end point of progression-free survival (PFS) in PD-L1–expressing platinum-resistant recurrent ovarian cancer, as well as for all comers. The secondary end point for OS was met in PD-L1–expressing disease at the previous interim analyses. Additionally, the safety profile of pembrolizumab in the trial was consistent with that observed in previous studies, with no new safety signals found.

According to the developers, findings from previous interim analyses of the KEYNOTE-B96 trial will be presented in a presidential symposium at the upcoming European Society for Medical Oncology (ESMO) Congress 2025.

“The results from the KEYNOTE-B96 trial mark the first time ever that an immune checkpoint inhibitor-based regimen has demonstrated the potential to help all patients with platinum-resistant recurrent ovarian cancer,” Gursel Aktan, MD, vice president of Global Clinical Development at Merck Research Laboratories, said in the news release.1 “These [patients have] a poor prognosis with limited options for treatment, and this impactful news is a testament to our tireless commitment to exploring new options for patients with gynecologic cancers who [have] a critical unmet need.”

The double-blind phase 3 trial enrolled approximately 643 patients and randomly assigned them to receive 400 mg of intravenous pembrolizumab every 6 weeks for up to 2 years plus intravenous paclitaxel at 80 mg/m2 on days 1, 8, and 15 of each 3-week cycle until unacceptable toxicity or disease progression.2 Those experiencing a severe hypersensitivity reaction to paclitaxel or an adverse effect (AE) requiring discontinuation of the agent were eligible to receive docetaxel at 75 mg/m2 every 3 weeks following sponsor consultation.

Bevacizumab was given at 10 mg/kg via intravenous infusion every 2 weeks until unacceptable toxicity, disease progression, or investigator decision. Placebo was given via infusion every 6 weeks for 18 cycles.

Other secondary end points of the phase 3 trial included PFS per RECIST v1.1 criteria based on blinded independent central review, incidence of AEs, incidence of study discontinuations, global health status, and health-related quality of life.

Those with histological confirmation of epithelial ovarian, fallopian tube, or primary peritoneal carcinoma; those who have received 1 to 2 prior lines of systemic therapy for ovarian cancer; and those with radiographic evidence of disease progression within 6 months after the last dose of platinum-based chemotherapy for their disease were eligible for enrollment on the trial. Additional inclusion criteria included an ECOG performance status of 0 or 1 within 3 days before random assignment, radiographically evaluable disease, and adequate organ function.

Patients ineligible for trial enrollment included those with nonepithelial cancers, borderline tumors, mucinous or seromucinous disease, malignant Brenner’s tumor, and undifferentiated carcinoma; those with primary refractory disease; or those who have experienced prior disease progression on paclitaxel alone. Additionally, those who had received more than 2 prior lines of therapy for ovarian cancer, those who had received prior anticancer therapy within 4 weeks of random assignment, and those who had received prior radiotherapy within 2 weeks of study entry were excluded from trial enrollment.

Pembrolizumab is not currently approved to treat ovarian cancer in the US.

References

1. Merck announces phase 3 KEYNOTE-B96 trial met secondary endpoint of overall survival (OS) in all comers population of patients with platinum-resistant recurrent ovarian cancer. News release. Merck. October 16, 2025. Accessed October 16, 2025. https://tinyurl.com/2emz6a2b
2. Pembrolizumab/​placebo plus paclitaxel with or without bevacizumab for platinum-resistant recurrent ovarian cancer (MK-3475-B96/​KEYNOTE-B96/​ENGOT-ov65). ClinicalTrials.gov. Updated July 14, 2025. Accessed October 16, 2025. https://tinyurl.com/56wswrxs