Clinical Trial of Keytruda and Lynparza Combination Fails to Meet Primary Endpoint for Treatment of Metastatic Nonsquamous Non-Small Cell Lung Cancer

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Merck revealed that its Phase III KEYLYNK-006 clinical trial, which tested a combination of Keytruda and Lynparza for the treatment of a subset of patients with metastatic nonsquamous non-small cell lung cancer (NSCLC), failed to meet the primary endpoint of improving overall survival (OS) and progression-free survival (PFS). According to the company, its trial compared Keytruda combined with chemotherapy with an additional round of Keytruda plus Lynparza vs. Keytruda with chemotherapy followed by maintenance chemotherapy. However, the safety profiles for both treatments were reported to be consistent with previous findings. Moving forward, Merck said that it plans on continuing to analyze data to share at a later date.¹

“As lung cancer continues to be the leading cause of cancer death worldwide, we are committed to exploring Keytruda-based combinations and novel candidates that may further help improve patient outcomes,” said Gregory Lubiniecki, MD, VP, 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. We sincerely thank the patients and investigators for their important contributions to this study.”

Back in December, Merck halted the KEYLYNK-008 trial, which was a separate study of the combination of Keytruda and Lynparza, citing a recommendation from an independent Data Monitoring Committee (DMC). Reportedly, this study also found no significant improvement in OS compared to Keytruda in combination with chemotherapy followed by Keytruda and placebo. Additionally, PFS, the study’s other primary endpoint, was not found to have a statistically significant improvement.²

“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, SVP, 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 Keytruda-based combinations and novel candidates for patients with lung cancer.”

At the same time, the combination also missed primary endpoints in patients with locally recurrent inoperable or metastatic triple-negative breast cancer (TNBC) who previously received induction with chemotherapy, based on findings from the Phase II KEYLYNK-009 study. These findings were presented at the 2023 San Antonio Breast Cancer Symposium.³

“In the intention-to-treat (ITT) population, results showed that the progression-free survival (PFS) per RECIST v1.1 criteria by blinded independent central review (BICR) was 5.5 months (95% CI, 4.2-8.3) with pembrolizumab/olaparib (n = 135) compared with 5.6 months (95% CI, 4.3-6.9) with pembrolizumab/chemotherapy (n = 136; HR, 0.98; 95% CI, 0.72-1.33; P = .4556),” according to a December 2023 article from OncLive. “The 6-month PFS rates were 47.8% (95% CI, 38.5%-56.5%) with pembrolizumab plus olaparib and 45.8% (95% CI, 36.8%-54.4%) with pembrolizumab plus chemotherapy; the 1-year PFS rates were 33.3% (95% CI, 24.5%-42.3%) and 29.3% (95% CI, 21.2%-37.8%), respectively.”

References

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. Merck. March 21, 2024. Accessed March 22, 2024. https://www.merck.com/news/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/

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. Merck. December 7, 2023. Accessed March 22, 2024. https://www.businesswire.com/news/home/20231207532705/en/Merck-Announces-KEYLYNK-008-Trial-Evaluating-KEYTRUDA%C2%AE-pembrolizumab-Plus-LYNPARZA%C2%AE-olaparib-for-Patients-With-Metastatic-Squamous-Non-Small-Cell-Lung-Cancer-to-Stop-for-Futility

3. Maintenance Pembrolizumab/Olaparib Misses Survival End Points in Locally Advanced or Metastatic TNBC. OncLive. December 6, 2023. Accessed March 22, 2024. https://www.onclive.com/view/maintenance-pembrolizumab-olaparib-misses-survival-end-points-in-locally-advanced-or-metastatic-tnbc