Pembrolizumab Combo Extends PFS in Platinum-Resistant Ovarian Cancer
Data from the KEYNOTE-B96 trial also show a significant overall survival improvement with pembrolizumab-based treatment in PD-L1–positive disease.
The safety profile of pembrolizumab in the KEYNOTE-B96 study was comparable with prior reports of the agent, and investigators observed no new safety signals.
The phase 3 KEYNOTE-B96/ENGOT-ov65 trial (NCT05116189) assessing pembrolizumab (Keytruda) plus paclitaxel with or without bevacizumab (Avastin) reached the primary end point of progression-free survival (PFS) among patients with platinum-resistant ovarian cancer across the all-comer and PD-L1–positive populations, according to a press release from Merck.1
After an independent data monitoring committee conducted pre-specified interim analyses, data showed that pembrolizumab-based treatment produced a clinically meaningful and statistically significant PFS improvement vs placebo plus chemotherapy with or without bevacizumab, regardless of PD-L1 expression. Additionally, the investigational combination elicited a statistically significant and clinically meaningful overall survival (OS) improvement among patients with PD-L1–positive disease, thereby meeting one of the trial’s secondary end points.
The safety profile of pembrolizumab in the KEYNOTE-B96 study was comparable with prior reports of the agent, and investigators observed no new safety signals.
Investigators will continue their assessment of OS across the full study population for a future analysis. Furthermore, they plan to present study findings at a future medical meeting and share them with regulatory authorities across the world.
“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, the developers of pembrolizumab, stated in the press release.1 “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.”
Investigators of the double-blind, randomized phase 3 KEYNOTE-B96 trial are assessing pembrolizumab plus chemotherapy with or without bevacizumab vs placebo/chemotherapy with or without bevacizumab among those with platinum-resistant ovarian cancer. An estimated population of 643 patients was randomly assigned to receive pembrolizumab at 400 mg intravenously every 6 weeks for approximately 2 years or a matched placebo in combination with paclitaxel at 80 mg/m2 intravenously on days 1, 8, and 15 of each 3-week cycle.2 Those with severe hypersensitivity reactions or toxicities associated with paclitaxel were eligible to receive docetaxel at 75 mg/m2 every 3 weeks. Additionally, patients could receive bevacizumab at 10 mg/kg intravenously of each 2-week cycle.
The trial’s primary end point was PFS per investigator assessment using RECIST v1.1 criteria. Secondary end points included PFS per blinded independent central review, OS, the number of patients who discontinued study therapy due to an adverse effect, global health status or quality of life, and time to deterioration.
Patients 18 years or older with histologically confirmed epithelial ovarian, fallopian tube, or primary peritoneal carcinoma and 1 or 2 prior lines of systemic therapy, including at least 1 platinum-containing therapy, were eligible for enrollment on the study. Other requirements for study entry included having radiographic evidence of progressive disease within 6 months after the last dose of platinum-based chemotherapy, an ECOG performance status of 0 or 1, and adequate organ function.
Those with nonepithelial cancers, borderline tumors, mucinous, seromucous that is predominantly mucinous, malignant Brenner’s tumor, or undifferentiated carcinoma histology were ineligible for study entry. Patients were also unable to enroll if they had prior disease progression on paclitaxel alone, prior radiotherapy within 2 weeks of beginning study therapy, or known active central nervous system metastases and/or carcinomatous meningitis.
References
- 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://tinyurl.com/4mafazvt
- 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://tinyurl.com/wn6vvk6a
