Pembrolizumab/Olaparib Misses Survival End Points in NSCLC Subgroup


The combination of pembrolizumab and olaparib did not appear to improve overall or progression-free survival in patients with nonsquamous non-small cell lung cancer.

lung with cancer cells: © catalin -

lung with cancer cells: © catalin -

First-line pembrolizumab (Keytruda) and maintenance olaparib (Lynparza) did not improve overall survival (OS) or progression-free survival (PFS) in patients with metastatic nonsquamous non-small cell lung cancer (NSCLC) compared with pembrolizumab plus chemotherapy, missing the coprimary end points of the phase 3 KEYLYNK-006 study (NCT03976323).1

A full analysis of the data is still ongoing and will be shared in the future.

“As lung cancer continues to be the leading cause of cancer death worldwide, we are committed to exploring [pembrolizumab]-based combinations and novel candidates that may further help improve patient outcomes,” said Gregory Lubiniecki, MD, vice president, global clinical development, Merck Research Laboratories, in a press release. “These results are an important reminder of how challenging it may be to treat these patients with metastatic nonsquamous non-small cell lung cancer.”

In December 2023, Merck halted the phase 3 KEYLYNK-008 study NCT03976362 investigating pembrolizumab plus olaparib in metastatic squamous NSCLC due to futility. At an interim analysis, the combination did not demonstrate improvements in OS compared with pembrolizumab plus placebo.2

About KEYLYNK-006

KEYLYNK-006 is a randomized, open-label, 2-phase, phase 3 study evaluating the anti-PD-1 agent pembrolizumab plus the poly-ADP ribose polymerase (PARP) inhibitor olaparib in patients with metastatic squamous NSCLC.1 The primary end points are PFS and OS, and secondary end points include incidence of adverse events and health-related quality of life.3

An estimated 1005 patients were enrolled in the initial induction phase, and 672 patients who experienced a complete response, partial response, or stable disease were further randomized to the maintenance phase.1 During the induction phase, patients received 200 mg of intravenous (IV) pembrolizumab plus pemetrexed plus investigator’s choice of platinum-based chemotherapy for 4 cycles. Patients who went onto the maintenance phase received either 200 mg IV pembrolizumab every 3 weeks plus 300 mg of oral olaparib twice daily or pembrolizumab plus maintenance pemetrexed. Maintenance therapy was continued for up to 31 cycles until progressive disease, physician decision, or intolerable toxicity.

Patients were eligible for study enrollment if they had histologically or cytologically confirmed nonsquamous stage IV NSCLC where EGFR-, ALK-, or ROS1-directed therapy was not indicated.3 Patients were also required to have a life expectancy of at least 3 months, an ECOG performance status of 0 or 1, adequate organ function, and not received prior systemic therapy for NSCLC. Exclusion criteria for KEYLYNK-006 included having an additional malignancy, active central nervous system metastases, hypersensitivity to the study agents, active autoimmune disease, or known hepatitis or HIV infection.

1. Merck provides update on phase 3 KEYLYNK-006 trial evaluating KEYTRUDA® (pembrolizumab) plus maintenance LYNPARZA® (olaparib) for certain patients with metastatic nonsquamous non-small cell lung cancer. News release. Merck. March 21, 2024. Accessed March 21, 2024.
2. Merck announces KEYLYNK-008 trial evaluating KEYTRUDA (pembrolizumab) plus LYNPARZA (olaparib) for patients with metastatic squamous non-small cell lung cancer to stop for futility. News release. Merck. December 7, 2023. Accessed March 21, 2024.
3. Study of pembrolizumab with maintenance olaparib or maintenance pemetrexed in first-line (1L) metastatic nonsquamous non-small-cell lung cancer (NSCLC) (MK-7339-006, KEYLYNK-006). Updated September 8, 2023. Accessed March 21, 2024.
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