1312MO Combining the antigen-presenting cell activator eftilagimod alpha (soluble LAG-3) and pembrolizumab: Overall survival data from the first line non-small cell lung carcinoma (NSCLC) cohort of TACTI-002 (phase II)

Eftilagimod alpha (E), a soluble LAG-3 protein, acts as an MHC class II agonist triggering activation of antigen-presenting cells (APC). Subsequently downstream T-cells (e.g. CD4/CD8) are recruited, possibly leading to stronger anti-tumor responses than with pembrolizumab (P) alone, especially in tumors non-overexpressing PD-L1. We hereby report initial overall survival (OS) results of the 1st line non-small cell lung carcinoma (NSCLC) cohort in TACTI-002. Patients (pts) with measurable 1st line metastatic NSCLC unselected for PD-L1 were recruited. Primary endpoint (EP) was objective response rate (ORR) by iRECIST. Secondary EPs included OS, ORR by RECIST 1.1, duration of response (DoR), progression free survival (PFS), safety & biomarkers. Pts received 30 mg E SC q2w for 8 cycles (1 cycle= 3 weeks) & then q3w up to 1 yr with P 200 mg IV q3w up to 2 yrs. Imaging was done q9w & assessed by investigator. PD-L1 was centrally assessed (22C3). The study was powered (80%) with a 1-sided alpha of 2.5% to detect an ORR increase from 23% (historical results for P) to 35%. From Mar 2019-Nov 2021, 114 pts enrolled using modified Simon’s two-stage design. Median follow up of 20.4 mo (cut-off Mar 31, 2023). Median age was 67 (44–85) & 74% were male. ECOG PS was 0 & 1 in 37% & 63% of pts. Pts had squamous (35%) or non-squamous (63%) carcinoma. All PD-L1 subgroups were represented; 77.8% had TPS <50%. Pts received median 9 (1–35) P & 13 (1–22) E doses. Median (m) OS unselected for PD-L1 was 22.6 mo (52.6% events) & mDoR was 21.6 mo. Onset of responses was quick (median: 2.1 mo). Comparable results by RECIST 1.1. Efficacy by PD-L1 shown in the table. Safety was presented prior at SITC 2022. Table: 1312MOEfficacy parameterORR, % [95% CI] by iRECISTmPFS, mo [95% CI] by iRECISTmOS, mo [95% CI]ITT (N=114); PD-L1 unselected40.4 [31.3–50.0]6.6 [4.6–9.8]22.6 [14.9–35.0]By PD-L1 TPS (N=90) ≥1% (N=58) <1% (N=32) 1–49% (N=38) ≥50% (N=20)48.3 [35.0–61.8] 31.3 [16.1–50.0] 44.7 [28.6–61.7] 55.0 [31.5–76.9]11.2 [6.3–16.6] 4.2 [2.1–6.2] 9.3 [4.4–15.7] 16.3 [4.0–43.9]25.0 [12.1–38.8] 15.5 [7.4–19.8] 23.4 [9.3–35.5] 38.8 [8.1–38.8] Open table in a new tab . E + P shows encouraging OS results in line with excellent ORR, PFS and DOR in 1st line NSCLC overall and in all PD-L1 subgroups. This combination warrants further late-stage clinical investigation.