A soluble LAG-3 protein (eftilagimod alpha) and an anti-PD-L1 antibody (avelumab) tested in a phase I trial: a new combination in immuno-oncology

Abstract

Background: Eftilagimod alpha (efti) is a major histocompatibility complex class II agonist activating antigen-presenting cells which leads to greater systemic type 1 T helper response and more cytotoxic CD8+ T-cell activation. This phase I trial evaluated the administration of efti, a soluble lymphocyte activation gene-3 (LAG-3) protein, combined with the anti-programmed death-ligand 1 (PD-L1) antibody avelumab in advanced solid tumors.

Patients and methods: Patients with heavily pretreated metastatic solid tumors received intravenous avelumab (800 mg) combined with subcutaneously administered efti (6 or 30 mg) for up to 12 cycles, followed by avelumab monotherapy. The primary endpoint was the assessment of the recommended phase II dose (RP2D) of efti in combination with avelumab.

Results: Twelve patients with different tumor entities were enrolled (six patients in each cohort). During treatment, no dose-limiting toxicities occurred, and the severity of most adverse events was grade 1 or 2. In total, nine serious adverse events were documented, resulting in a fatal outcome in two cases, but none of them were assessed to be treatment related. Five patients (42%) achieved partial response. The median progression-free survival was 1.96 months and the median overall survival was not reached, with a 12-month survival rate of 75%.

Conclusion: Subcutaneously administered efti plus avelumab was well tolerated, and efti of 30 mg was determined to be RP2D. The activity is promising and warrants further investigation in future phase II trials.

Keywords: LAG-3 protein; anti-PD-L1; eftilagimod alpha; metastatic solid tumors.

Figure 1

Consort diagram. All patients enrolled who received at least one dose of efti were included in the full analysis set, which is identical with the safety set. efti, eftilagimod alpha.

Figure 2

Best overall response according to RECIST version 1.1 of individual patients. (A) Best % sum change of tumor measurement compared with baseline for each patient, except patient 018, who died before the first assessment. (B) Timeline of response for each patient. Triangles at the end of the bars represent the survival status. C1, cohort 1; C2, cohort 2; PD, progression disease; PR, partial response; SD, stable disease.