Clinical trialPhase 3Ovarian cancer

Pembrolizumab plus weekly paclitaxel in platinum-resistant recurrent ovarian cancer (ENGOT-ov65/KEYNOTE-B96): a multicentre, randomised, double-blind, phase 3 study

Lancet · 2026643 patients (322 pembrolizumab–paclitaxel and 321 placebo–paclitaxel)

Colombo N, Zsiros E, Parma G, Rulli E, Sebastianelli A, Bidzinski M, et al. Lancet. 2026. 407:1525-1537

Study type: Clinical trial
Study name: KEYNOTE-B96 (ENGOT-ov65)
Phase: Phase 3
Design: Randomised, double-blind, placebo-controlled trial (1:1) at 187 centres in 25 countries
Sample size: 643 patients (322 pembrolizumab–paclitaxel and 321 placebo–paclitaxel)
Source: Lancet · 2026
Trial registration: NCT05116189

In plain words

In this study, women whose ovarian cancer had come back less than 6 months after platinum chemotherapy (platinum-resistant) received weekly paclitaxel (with or without bevacizumab) together with the immunotherapy drug pembrolizumab or with a placebo. Adding pembrolizumab kept the disease under control for longer and also helped patients live longer; in patients whose tumour had PD-L1, median survival rose from 14 to about 18 months. Serious side effects were slightly more common. Decisions about treatment should be made with your own doctor.

Key results

18.2 months vs 14.0 months

Median overall survival (PD-L1 CPS ≥1)

HR 0.76 (0.61–0.94); P=0.0053; second interim analysis

17.7 months vs 14.0 months

Median overall survival (whole population)

HR 0.82 (0.69–0.97); P=0.011; final analysis

8.3 months vs 7.2 months

Median progression-free survival (CPS ≥1)

HR 0.72 (0.58–0.89); P=0.0014

8.3 months vs 6.4 months

Median progression-free survival (whole population)

HR 0.70 (0.58–0.84); P<0.0001

68% vs 55%

Treatment-related grade ≥3 adverse events

217 of 320 vs 176 of 318 patients

Drugs in this study:Bevacizumab (Avastin)Paclitaxel (Taxol)Pembrolizumab (Keytruda)

Dose and schedule cards

Pembrolizumab + weekly paclitaxel ± bevacizumab (KEYNOTE-B96)

Platinum-resistant recurrence (progression within 6 months after the last platinum) after 1 to 2 prior regimens, PD-L1 CPS ≥1 (22C3); no autoimmune disease requiring systemic treatment in the past 2 yearsOn the page “Ovarian cancer” · Platinum-resistant recurrence

Drug	Dose	Route	Schedule
Pembrolizumab	400 mg every 6 weeks (or 200 mg every 3 weeks)	IV, 30 minutes; before paclitaxel	Day 1
Paclitaxel	80 mg/m²	IV	Days 1, 8 and 15 every 3 weeks
Optional
Bevacizumab	10 mg/kg	IV	Day 1 every 2 weeks

Cycle length: Paclitaxel in 21-day cycles (no rest week); pembrolizumab every 6 weeks
Duration: Pembrolizumab until progression, unacceptable toxicity or up to 24 months

Grade 3 or higher treatment-related adverse events: 68% vs 55%. Monitor liver enzymes, creatinine and thyroid function at baseline and periodically.

On the page “Ovarian cancer” · Platinum-resistant recurrence

Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.

Treatment arms and regimens

1Pembrolizumab with paclitaxel

Pembrolizumab 400 mg IV every 6 weeks for up to 18 cycles with paclitaxel 80 mg/m² IV on days 1, 8 and 15 of each 21-day cycle; bevacizumab 10 mg/kg every 2 weeks was allowed at the investigator's discretion.

2Placebo with paclitaxel

Placebo (saline) IV every 6 weeks for up to 18 cycles with paclitaxel 80 mg/m² on days 1, 8 and 15 of each 21-day cycle; bevacizumab 10 mg/kg every 2 weeks was allowed at the investigator's discretion.

Source of the regimen details: Abstract of the paper and the FDA label for Keytruda (DailyMed, section 14.21; maximum 24 months)

Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.

Study population

Adults with epithelial ovarian, fallopian tube or primary peritoneal carcinoma who had received 1 to 2 previous systemic regimens (at least one platinum-based) and had progressed 6 months or less after the last platinum-based regimen.

Endpoints

Primary endpoint: investigator-assessed progression-free survival per RECIST 1.1; key secondary endpoint: overall survival.

Safety and side effects

Treatment-related grade 3 or higher adverse events occurred in 68% of the pembrolizumab group and 55% of the placebo group; most common adverse events: anaemia, peripheral neuropathy, alopecia, fatigue and nausea. Treatment-related deaths: 4 patients (1%) in the pembrolizumab group (colitis, interstitial lung disease, acute myeloid leukaemia and intestinal perforation) and 5 patients (2%) in the placebo group.

Clinical significance and place in guidelines

KEYNOTE-B96 is the first phase 3 trial to show an overall survival improvement from adding immunotherapy to chemotherapy in platinum-resistant ovarian cancer. In February 2026 the FDA approved pembrolizumab with paclitaxel, with or without bevacizumab, for platinum-resistant patients with PD-L1 expression (CPS ≥1) who have received 1 to 2 previous regimens.

Limitations

The absolute progression-free survival benefit was small (about 1 to 2 months) and grade 3 or higher adverse events were more frequent in the pembrolizumab group. Use of bevacizumab was not randomised.

Original article (DOI)PubMed ClinicalTrials.gov

This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.