Merck’s Keytruda Continues NSCLC Losing Streak with Phase III Flop

Merck research laboratories_iStock, hapabapa

Pictured: Merck Research Laboratories in South San Francisco, California/iStock, hapabapa 

Merck on Thursday announced that its blockbuster PD-1 inhibitor Keytruda (pembrolizumab) in combination with AstraZeneca’s PARP inhibitor Lynparza (olaparib) fell short of its dual primary endpoints in the Phase III KEYLYNK-006 trial, unable to significantly improve survival outcomes in specific patients with metastatic non-squamous non-small cell lung cancer.

KEYLYNK-006 is a randomized, open-label and two-phase study that enrolled 1,005 patients who were treated with Keytruda plus chemotherapy with pemetrexed and carboplatin or cisplatin. Participants were then randomly given maintenance therapy with either Keytruda plus Lynparza or Keytruda plus chemotherapy.

Without providing specific data Thursday, Merck disclosed that patients in the Keytruda-Lynparza arm did not see significantly better overall survival (OS) and progression free survival (PFS)—KEYLYNK-006’s dual primary endpoints—compared with chemotherapy controls.

The study focused on metastatic non-squamous non-small cell lung cancer (NSCLC) patients who did not carry EGFR, ALK or ROS1 genomic tumor aberrations. KEYLYNK-006 assessed the efficacy and safety of the Keytruda-Lynparza regimen as a first-line treatment option in these patients.

Gregory Lubiniecki, vice president of global clinical development at Merck Research Laboratories, in a statement said that these results “are an important reminder of how challenging it may be to treat” patients with metastatic non-squamous NSCLC.

In terms of safety, the profiles for Keytruda and Lynparza were consistent with what had been previously documented in other trials.

A complete analysis of data from KEYLYNK-006 is ongoing, according to Merck. The company will share its findings with the scientific community in the future.

Thursday’s disappointing readout continues Keytruda’s losing streak in NSCLC. In December 2023, the pharma reported back-to-back failures for its PD-1 inhibitor in the indication.

In the Phase II KeyVibe-002 trial, Merck used Keytruda combined vibostolimab—an anti-TIGIT antibody—for the treatment of metastatic NSCLC patients whose disease had progressed after immunotherapy and platinum-doublet chemotherapy. Results showed that, with or without docetaxel, the investigational regimen yielded no significant benefits on patients’ PFS and OS.

Merck at the time also announced that Keytruda failed its KEYLYNK-008 trial which, as in the case of KEYLYNK-006, combined the PD-1 inhibitor with Lynparza. During a planned interim analysis, an independent data monitoring committee found that the investigational regimen did not significantly improve OS in metastatic squamous NSCLC patients, forcing the pharma to discontinue the study.

Keytruda is a humanized monoclonal antibody that blocks the PD-1 signaling, which in turn prevents cancer cells from evading the body’s innate anti-cancer immune response. The therapy was first approved in 2014 for advanced melanoma, but has since picked up a plethora of other oncology indications and has become a fundamental cancer therapy.

Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Reach out to him on LinkedIn or email him at tristan@tristanmanalac.com or tristan.manalac@biospace.com.

Editor's note: The article has been updated to clarify that Keytruda, when used with AstraZeneca’s PARP inhibitor Lynparza (olaparib), did not significantly improve overall and progression-free survival in specific patients with metastatic non-squamous non-small cell lung cancer.

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