Pembrolizumab-Based Regimen Yields PFS Benefit in Platinum-Resistant Ovarian Cancer

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Pembrolizumab (Keytruda) plus paclitaxel with or without bevacizumab (Avastin) significantly improved progression-free survival (PFS) vs placebo plus chemotherapy with or without bevacizumab in patients with platinum-resistant recurrent ovarian cancer regardless of PD-L1 status, meeting the primary end point of the phase 3 KEYNOTE-B96 trial/ENGOT-ov65 trial (NCT05116189).1

Data from the prespecified interim analysis of the trial, which was conducted by an independent data monitoring committee, also showed that the pembrolizumab-containing regimen generated a statistically significant and clinically meaningful overall survival (OS) benefit in patients with PD-L1–expressing tumors, defined as those with a PD-L1 combined positive score of 1 or higher. The trial is ongoing, and OS findings for the overall study population will be evaluated in a future analysis.

The safety profile of pembrolizumab in this trial was consistent with that seen in previously reported studies, and investigators observed no new safety signals, according to a news release. Findings from KEYNOTE-B96 will be presented at an upcoming medical conference and shared with global regulatory authorities.

“This marks the first time a [pembrolizumab]-based regimen has shown the ability to help certain patients with platinum-resistant ovarian cancer live longer, and the first time an immune checkpoint inhibitor–based regimen has demonstrated an OS benefit in ovarian cancer,” Gursel Aktan, MD, PhD, vice president of global clinical development at Merck Research Laboratories, stated in a news release. “The positive results from this trial add to the growing body of evidence supporting the potential benefit of [pembrolizumab] across gynecological cancers, including this difficult-to-treat form of ovarian cancer for which patients are in need of new options.”

The randomized, double-blind KEYNOTE-B96 trial enrolled approximately 643 patients at least 18 years of age with histologically confirmed epithelial ovarian, fallopian tube, or primary peritoneal carcinoma who had previously received 1 or 2 prior lines of systemic therapy for ovarian cancer, including at least 1 prior platinum-based therapy.1,2 Patients needed to have platinum-resistant disease, defined as radiographic evidence of disease progression within 6 months after their last dose of platinum-based chemotherapy for ovarian cancer; be a candidate for paclitaxel (and bevacizumab, if using); have an ECOG performance status of 0 or 1 within 3 days before random assignment; have radiographically evaluable disease that was either measurable or nonmeasurable per RECIST 1.1 criteria, as assessed by a local site investigator; provide an archival tumor tissue sample or a newly obtained core or incisional/excisional biopsy of a tumor lesion that had not previously been irradiated; and have adequate organ function.2

Patients were randomly assigned to receive pembrolizumab in combination with paclitaxel with or without bevacizumab; or placebo plus paclitaxel with or without bevacizumab. Pembrolizumab was administered intravenously (IV) at 400 mg every 6 weeks for approximately 2 years. IV paclitaxel was given at 80 mg/m2 on days 1, 8, and 15 of each 3-week cycle until intolerance or disease progression. In those who received it, IV bevacizumab was administered at 10 mg/kg every 2 weeks until intolerance, disease progression, or at the investigator’s discretion.

The primary end point was investigator-assessed PFS per RECIST 1.1 criteria. Secondary end points included OS, blinded independent central review–assessed PFS per RECIST 1.1 criteria, rate of adverse effects (AEs), rate of study discontinuation due to AEs, change from baseline in Global Health Status (GHS)/Quality of Life (QOL) Score per the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30), time to deterioration in GHS/QOL Score per the EORTC QLQ-C30, change from baseline in the Abdominal and Gastrointestinal (GI) Symptoms Score per the EORTC Quality of Life Questionnaire-Ovarian Cancer (QLQ-OV28) Abdominal/GI Symptom Scale, and time to deterioration in the Abdominal and GI Symptoms Score per the EORTC QLQ-OV28 Abdominal/GI Symptom Scale.

References

1. Merck announces phase 3 KEYNOTE-B96 trial met primary endpoint of progression-free survival (PFS) in patients with platinum-resistant recurrent ovarian cancer whose tumors expressed PD-L1 and in all comers. News release. Merck. May 15, 2025. Accessed May 15, 2025. https://www.merck.com/news/merck-announces-phase-3-keynote-b96-trial-met-primary-endpoint-of-progression-free-survival-pfs-in-patients-with-platinum-resistant-recurrent-ovarian-cancer-whose-tumors-expressed-pd-l1-and-in-all-c/
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 March 7, 2025. Accessed May 15, 2025. https://clinicaltrials.gov/study/NCT05116189