Trial results for the KEYLYNK-001 study (NCT03740165) investigating pembrolizumab (Keytruda) in combination with olaparib (MK-7339) and chemotherapy for the first-line treatment of advanced epithelial ovarian cancer were posted on ClinicalTrials.gov on 2025-09-12. The study showed that the quadruple combination extended median progression-free survival (PFS) to 23.9 months in participants with PD-L1 positive tumors, compared to 15.2 months for chemotherapy alone.

Background

The KEYLYNK-001 study, also known as "Study of Chemotherapy With Pembrolizumab (MK-3475) Followed by Maintenance With Olaparib (MK-7339) for the First-Line Treatment of Women With BRCA Non-mutated Advanced Epithelial Ovarian Cancer (EOC) (MK-7339-001/KEYLYNK-001/ENGOT-ov43/GOG-3036)," aimed to assess the efficacy and safety of treatment with carboplatin/paclitaxel plus pembrolizumab and maintenance olaparib in women with epithelial ovarian cancer (EOC), fallopian tube cancer, or primary peritoneal cancer.

Trial design

The KEYLYNK-001 study (NCT03740165) was a Phase 3, randomized trial that enrolled 1367 participants. The study investigated treatment combinations for women with ovarian cancer, fallopian tube cancer, or peritoneal neoplasms. Participants received either carboplatin + paclitaxel, carboplatin + paclitaxel + pembrolizumab, or carboplatin + paclitaxel + pembrolizumab + olaparib. The primary study hypotheses focused on the superiority of the combination of pembrolizumab plus carboplatin/paclitaxel followed by continued pembrolizumab and maintenance olaparib compared to carboplatin/paclitaxel alone with respect to Progression-Free Survival (PFS) per RECIST 1.1.

Key results

The trial results demonstrated differences in progression-free survival (PFS) and overall survival (OS) across the treatment arms. For participants with Programmed Death-Ligand 1 (PD-L1) positive tumors (Combined Positive Score [CPS]≥10):

A hazard ratio (HR) analysis comparing carboplatin + paclitaxel + pembrolizumab + olaparib to carboplatin + paclitaxel showed an HR of 0.66 (95% Confidence Interval: 0.53 to 0.83) with a p-value of 0.0002 for PFS in PD-L1 positive tumors.

For all participants, regardless of PD-L1 status:

A hazard ratio (HR) analysis comparing carboplatin + paclitaxel + pembrolizumab + olaparib to carboplatin + paclitaxel showed an HR of 0.71 (95% Confidence Interval: 0.61 to 0.84) with a p-value of 0.0001 for PFS in all participants.

Regarding Overall Survival (OS):

The hazard ratio analyses for OS did not show statistically significant differences between the combination therapies and chemotherapy alone. For example, comparing carboplatin + paclitaxel + pembrolizumab + olaparib to carboplatin + paclitaxel in all participants, the HR was 0.94 (95% Confidence Interval: 0.72 to 1.22) with a p-value of 0.3107.

What this means

The results from the KEYLYNK-001 trial indicate that the combination of pembrolizumab and olaparib with chemotherapy significantly improved progression-free survival in women with advanced epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer, both in PD-L1 positive and overall populations. While a significant PFS benefit was observed, the trial did not demonstrate a statistically significant improvement in overall survival with the combination therapies compared to chemotherapy alone. These findings provide important data for clinicians considering first-line treatment strategies for these cancers, highlighting a PFS advantage with the quadruple regimen.

Source

The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for study NCT03740165, titled "Study of Chemotherapy With Pembrolizumab (MK-3475) Followed by Maintenance With Olaparib (MK-7339) for the First-Line Treatment of Women With BRCA Non-mutated Advanced Epithelial Ovarian Cancer (EOC) (MK-7339-001/KEYLYNK-001/ENGOT-ov43/GOG-3036)," were posted on 2025-09-12 on clinicaltrials.gov.