Merck Halts Phase 3 Pembrolizumab/Olaparib Trial in NSCLC

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The phase 3 KEYLYNK-008 trial investigating pembrolizumab and olaparib in metastatic squamous non–small cell lung cancer will be stopped due to futility.

Holographic concept of lung cancer display, lung disease, treatment of lung cancer: © catalin - stock.adobe.com

Holographic concept of lung cancer display, lung disease, treatment of lung cancer: © catalin - stock.adobe.com

KEYLYNK-008 (NCT03976362), a phase 3 trial assessing pembrolizumab (Keytruda) with the poly ADP ribose polymerase (PARP) inhibitor olaparib (Lynparza) in patients with metastatic squamous non–small cell lung cancer is being discontinued, according to a press release from Merck.1

This comes off a recommendation from an independent data monitoring committee that reviewed an interim analysis from the KEYLYNK-008 trial. The interim analysis did not demonstrate improvements in overall survival (OS) with the combination of pembrolizumab and olaparib, one of the trial’s primary end points, compared with pembrolizumab and placebo. Further, the improvement in progression-free survival (PFS), the other primary end point, was not significantly significant at the time of the interim analysis.

The safety profile was consistent with the known profiles of the agents that have been reported in previous studies. Findings from the KEYLYNK-008 study will be presented at an upcoming medical meeting.

“While there have been significant scientific advancements in lung cancer research in recent years, unmet needs remain for patients with advanced non–small cell lung cancer,” said Marjorie Green, MD, senior vice president and head of late-stage oncology, global clinical development, Merck Research Laboratories, in a press release. “We sincerely thank the patients and investigators for their participation in this study, and we will continue to advance our clinical development program to evaluate [pembrolizumab]-based combinations and novel candidates for patients with lung cancer.”

Other KEYLYNK studies are still ongoing to evaluate pembrolizumab-based combinations in NSCLC. These include the phase 3 KEYLYNK-006 (NCT03976323) trial investigating pembrolizumab with maintenance olaparib or maintenance pemetrexed as a first-line therapy in metastatic nonsquamous NSCLC. The study is active but not currently enrolling, and the primary end points are PFS and OS.

KEYLYNK-006 has an enrollment of 1005 patients who undergo an induction phase of pembrolizumab plus pemetrexed and platinum-based chemotherapy, followed by a randomized maintenance phase of pembrolizumab plus olaparib or pembrolizumab plus maintenance pemetrexed.2

The KEYLYNK-012 (NCT04380636) is an active and currently enrolling phase 3 trial of pembrolizumab with concurrent chemoradiation followed by pembrolizumab with or without olaparib in stage III NSCLC. The primary end points are PFS and OS.

Patients are randomized into an experimental pembrolizumab plus chemoradiation to pembrolizumab plus placebo arm, an experimental pembrolizumab plus chemoradiation to pembrolizumab and olaparib arm, or an active comparator arm of chemoradiation followed by durvalumab (Imfinzi). The study has an estimated enrollment of 870 patients.3

REFERENCES:
1. 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 December 7, 2023. https://tinyurl.com/2am3tnaj
2. 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). ClinicalTrials.gov. Updated September 8, 2023. Accessed December 7, 2023. https://clinicaltrials.gov/study/NCT03976323
3. Study of pembrolizumab with concurrent chemoradiation therapy followed by pembrolizumab with or without olaparib in stage III non–small cell lung cancer (NSCLC) (MK-7339-012/KEYLYNK-012). ClinicalTrials.gov. Updated December 7, 2023. Accessed December 7, 2023. https://clinicaltrials.gov/study/NCT04380636
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