Eftilagimod Alpha Plus Pembrolizumab in First-Line Metastatic Non–Small Cell Lung Cancer: Results From a PD-L1–Unselected Population in the TACTI-002 Study

PURPOSE Eftilagimod alpha (efti), an antigen-presenting cell (APC) activator, may overcome PD-1/PD-L1 inhibitor primary resistance. This phase II study investigated efti plus pembrolizumab treatment in patients with first-line metastatic non–small cell lung cancer (NSCLC) unselected for PD-L1. METHODS Patients, naïve to systemic therapy in the metastatic setting, received efti (30 mg subcutaneously every 2 weeks for eight 3-week cycles, then every 3 weeks up to 54 weeks) plus pembrolizumab (200 mg intravenously every 3 weeks for up to 105 weeks). The primary end point was objective response rate (ORR) by immune RECIST. Secondary end points included duration of response (DoR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and tolerability. Exploratory end points included identification and characterization of biomarkers. PD-L1 tumor proportion score (TPS) was assessed centrally. RESULTS In the intention-to-treat population (n = 114), the median age was 67 years (range, 44-85), 73.7% was male, and 62.3% had an Eastern Cooperative Oncology Group performance status score of 1. Most patients (77.8%) had low/negative (<50%) PD-L1 TPS. The unconfirmed ORR (iRECIST) was 40.4%, leading to a confirmed ORR of 35.1%. The median DoR was 21.6 months, the DCR was 72.8%, and the median PFS (iRECIST) was 6.6 months. The median OS was 20.2 months, with 44.7% patients alive at 24 months. Antitumor activity was seen across all PD-L1 levels. A low proportion of patients had treatment-related adverse events leading to permanent discontinuation (8.8%). CONCLUSION The APC activator, efti, on top of pembrolizumab was well tolerated and showed encouraging antitumor activity in patients with first-line NSCLC irrespective of tumor PD-L1 expression.