Phase III Trial of Keytruda Plus Lynparza for NSCLC Stopped Due to Futility

Merck has announced that it will halt the Phase III KEYLYNK-008 trial evaluating Keytruda (pembrolizumab) plus chemotherapy and maintenance Lynparza (olaparib; AstraZeneca, MSD) in patients with metastatic squamous non-small cell lung cancer (NSCLC).

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The announcement follows a review of data from a planned interim analysis conducted by an independent Data Monitoring Committee (DMC). The DMC found that Keytruda in combination with chemotherapy followed by Keytruda plus Lynparza did not produce an improved overall survival (OS) benefit vs. Keytruda in combination with chemotherapy followed by Keytruda plus a placebo, which was one of the KEYLYNK-008 trial’s dual primary endpoints. The other primary endpoint of the KEYLYNK-008 trial was progression-free survival (PFS), which the DMC did not deem as statistically significant at the second interim analysis; however, the committee did observe a numerical improvement vs. the placebo cohort.

“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,” Marjorie Green, MD, senior vice president and head of late-stage oncology, global clinical development, Merck Research Laboratories, said 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 Keytruda-based combinations and novel candidates for patients with lung cancer.”

The randomized, triple-blind, Phase 3 KEYLYNK-008 trial (NCT03976362) analyzed the combination in an estimated 857 patients with NSCLC. Patients were administered Keytruda at 200 mg intravenously (IV) every three weeks for four cycles with carboplatin plus either paclitaxel or nab-paclitaxel every three weeks in the trial’s induction phase. For the maintenance phase, patients who experienced a partial or complete response or who had stable disease following the completion of four cycles of induction therapy were randomly assigned to receive Keytruda at 200 mg IV every three weeks for up to 31 cycles plus maintenance Lynparza at 300 mg orally twice daily or maintenance placebo until progressive disease, physician decision, or intolerable toxicity. The trial’s secondary endpoints included safety and health-related quality of life assessments.

In terms of safety, the profile of the combination was consistent with previously observed findings for the individual therapies with no new safety signals identified.

Keytruda is an anti-programed death receptor-1 (PD-1) therapy that improves the immune system's ability to detect and fight tumor cells. The humanized monoclonal antibody blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, which leads to the activation of T lymphocytes that could affect tumor and healthy cells.

To date, more than 1600 trials are evaluating Keytruda across a range of cancer types and treatment settings. Keytruda also has approved indications in melanoma; non-small cell lung cancer; head and neck squamous cell cancer; classical Hodgkin lymphoma; primary mediastinal large B-cell lymphoma; urothelial carcinoma; gastric cancer; microsatellite instability-high or mismatch repair deficient cancer; microsatellite instability-high or mismatch repair deficient colorectal cancer; esophageal cancer; cervical cancer; hepatocellular carcinoma; Merkel cell carcinoma; renal cell carcinoma; endometrial carcinoma; tumor mutational burden-high cancer; cutaneous squamous cell carcinoma; and triple-negative breast cancer.

Lynparza is a poly (ADP-ribose) polymerase (PARP) inhibitor indicated as first-line maintenance for BRCAm advanced ovarian cancer; first-line maintenance HRD-positive advanced ovarian cancer in combination with bevacizumab; maintenance BRCA-mutated recurrent ovarian cancer; adjuvant treatment of gBRCAm, HER2-negative, high-risk early breast cancer; gBRCAm, HER2-negative metastatic breast cancer; first-line maintenance gBRCAm metastatic pancreatic cancer; HRR gene-mutated metastatic castration-resistant prostate cancer; BRCAm metastatic castration-resistant prostate cancer in combination with abiraterone and prednisone or prednisolone.

Merck said it will present the data from the trial at an upcoming scientific congress.

Reference

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. Merck. News release. December 7, 2023. https://www.merck.com/news/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/