Results from a phase II study of eftilagimod alpha (soluble LAG-3 protein) and pembrolizumab in patients with PD-L1 unselected metastatic non-small cell lung carcinoma

Abstract

Background: Eftilagimod alpha (efti) is a soluble LAG-3 protein that binds to a subset of MHC class II molecules to mediate antigen presenting cell (APC) activation and CD8 T-cell activation. The stimulation of the dendritic cell network and subsequent T cell recruitment with efti may lead to stronger anti-tumor responses in combination than observed with pembrolizumab alone. We hereby report results of the 1st line non-small cell lung carcinoma (NSCLC) part of the phase II trial (NCT03625323). Methods: Patients (pts) with untreated, immunotherapy naïve, advanced NSCLC unselected for PD-L1 expression were recruited into part A. The study used a Simon's 2-stage design (17 pts planned for stage 1 and 19 pts for stage 2), with objective response rate (ORR) by iRECIST as the primary endpoint (EP). Secondary EPs include tolerability, disease control rate (DCR), progression free survival (PFS), overall survival (OS), PK, PD and immunogenicity. Efti is administered as 30 mg subcutaneous injection every 2 wks for 8 cycles and then every 3 wks for 9 cycles with pembrolizumab (200 mg intravenous infusion every 3 wks for up to 2 yrs). Imaging was performed every 8 weeks locally and with blinded independent central review (BICR) retrospectively. The study was approved by ethic committees and institutional review boards. Results: In total 36 pts were enrolled. At data cut-off (Jan 2021; median FU of 14 months), the median age was 69 yrs (range 53-84) and 69 % were male. The ECOG PS 0 and 1 was 42% and 58% respectively. Patients had squamous (42%) and non-squamous (58%) NSCLC and 95% presented with metastatic disease. All PD-L1 subgroups (TPS < 1 %, ≥ 1 % to ≤49 %; ≥50 %) were represented with 36% pts having ≥50% TPS. Pts received a median of 7.0 (range 1 – 31) pembrolizumab and 11.5 (range 1-22) efti administrations. Responses as per BICR and local read are shown in the table. ORR (local, iRECIST) by different PD-L1 subgroups was 27% for pts with TPS<1%, 39 % for TPS ≥1 %and 54% for ≥50 % TPS. Median PFS (n=36) was 8.2 months while median OS was not yet reached. The most common (> 20 %) treatment emergent adverse events (AEs) were asthenia (47 %), cough (36 %), decreased appetite (36 %), dyspnea (32 %), pruritus (31 %), fatigue (28 %), diarrhea (25 %), anemia (25 %), constipation (25 %) and back pain (22%). Two patients discontinued treatment due to adverse reactions (Grade 4 immune-mediated hepatitis, Grade 3 AST+ALT increase). Conclusions: Efti in combination with pembrolizumab is safe and shows encouraging antitumor activity in 1st line advanced NSCLC patients across all PD-L1 (TPS) levels.