Keytruda's Phase III Failure in NSCLC Continues

Merck's Keytruda, a widely recognized PD-1 inhibitor, and AstraZeneca’s PARP inhibitor Lynparza, have not met their primary goals in the Phase III KEYLYNK-006 trial. The combination therapy was intended to enhance the survival of patients with metastatic non-squamous non-small cell lung cancer (NSCLC) but did not show significant improvements in overall survival (OS) and progression-free survival (PFS) when compared to chemotherapy.

The KEYLYNK-006 trial was a randomized, open-label study that included 1,005 participants. These patients were initially treated with Keytruda along with chemotherapy and then randomly assigned to receive either Keytruda combined with Lynparza or Keytruda with further chemotherapy as maintenance therapy.

Merck did not release specific data but highlighted that the Keytruda-Lynparza combination did not yield the anticipated benefits in terms of OS and PFS. The trial specifically targeted metastatic NSCLC patients without EGFR, ALK, or ROS1 genomic tumor aberrations and aimed to evaluate the efficacy and safety of the Keytruda-Lynparza regimen as a first-line treatment.

Gregory Lubiniecki, a vice president at Merck Research Laboratories, emphasized the complexity of treating metastatic non-squamous NSCLC patients, suggesting that the recent findings underscore the challenges in this area.

The safety profiles of both Keytruda and Lynparza were found to be in line with past documentation from other trials. Merck is currently conducting a comprehensive analysis of the KEYLYNK-006 data and plans to share the results with the scientific community at a later date.

This outcome adds to Keytruda's series of setbacks in treating NSCLC. In December 2023, Merck reported failures in two trials involving Keytruda. The Phase II KeyVibe-002 trial combined Keytruda with an anti-TIGIT antibody, vibostolimab, for patients with metastatic NSCLC whose disease had progressed. The results indicated no significant improvements in PFS and OS. Additionally, the KEYLYNK-008 trial, similar to KEYLYNK-006, combined Keytruda with Lynparza but did not show significant improvements in OS for metastatic squamous NSCLC patients, leading to the discontinuation of the study.

Keytruda is a monoclonal antibody that targets the PD-1 pathway, preventing cancer cells from evading the immune system. Initially approved for melanoma in 2014, it has since been approved for various cancer types and has become a cornerstone in cancer therapy.