A phase III placebo-controlled study of eftilagimod alfa plus pembrolizumab and chemotherapy in metastatic non-small cell lung cancer.

backgroundAlthough immune checkpoint inhibitors (ICIs) form the cornerstone of first-line treatment for non-small cell lung cancer (NSCLC), the challenge remains to improve patients' long-term outcomes. Eftilagimod alfa (efti) activates antigen-presenting cells, triggering T cell activation and a sustained immune response. Prior studies combining efti with an ICI, pembrolizumab, have shown encouraging efficacy, especially in PD-L1 low (tumor proportion score [TPS] 1-49%) and negative (<1%) tumors. TACTI-004 is a global double-blinded, randomized, placebo-controlled phase III study investigating efti plus standard-of-care (SoC: pembrolizumab plus chemotherapy) in first-line NSCLC, regardless of PD-L1 expression (TPS 0-100%). PATIENTS AND

methodsAbout 756 participants with squamous or non-squamous first-line NSCLC, not amenable to EGFR/ROS1/ALK-targeted therapy, will be randomized to receive either efti plus SoC or placebo plus SoC. The dual primary endpoint is progression-free survival and overall survival. Key secondary endpoints include objective response rate, duration of response and safety. Participants will receive 30 mg efti subcutaneously every 2 weeks (q2w) for 24 weeks, then q3w and pembrolizumab 200 mg intravenously q3w, both for up to 2 years. Chemotherapy choice will be histology-dependent.

conclusionsTACTI-004 will evaluate whether efti can mitigate resistance to ICIs when added to SoC in NSCLC, irrespective of PD-L1 tumor status. CLINICAL

trial registrationwww.clinicaltrials.gov identifier is NCT06726265.