135P - Soluble PD-L1 (sPD-L1) as a predictive biomarker in patients with non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs) in the first-line setting

Background

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death in the world. Immune checkpoint inhibitors (ICIs) have improved outcomes but challenges remain as only 20% of patients present with prolonged benefit. Soluble PD-L1 (sPD-L1) has shown potent biomarker potential to predict response to ICIs in NSCLC. Herein, we further examine the biomarker potential of sPD-L1 in patients with NSCLC treated in the first-line setting with ICIs.

Methods

Patients with advanced NSCLC treated with ICIs were prospectively enrolled in two academic centers (Cohort #1 and #3). A historical cohort of patients with advanced NSCLC treated with first-line chemotherapy (CT) was included (Cohort #2). Plasma from patients was collected at baseline (before treatment) and at first tumour evaluation (on treatment). sPD-L1 was measured with a commercially available ELISA kit. All samples and controls were measured in duplicate. sPD-L1 levels were measured at baseline and on treatment and compared to overall response rate (ORR), durable clinical benefit (DCB), progression free survival (PFS), overall survival (OS). A549 and H596 cell-lines were cultured as per usual practice. PBMCs were obtained from healthy subjects.

Results

Cohort #1, 2 and 3 were comprised of 32, 45 and 34 patients. Baseline sPD-L1 levels were significantly higher in non-responders (NR) than responders (R) in Cohort #2 (59.65 pg/ml vs 30.40 pg/ml (p=0.0233). On treatment sPD-L1 levels were significantly higher in NR in Cohort #1 and #2: 14.74 pg/ml and 4.45, p=0.0138 and 79.65 pg/ml vs 29.40 pg/ml, p=0.0009. Across the cohorts, 87.5%, 59% and 64% of R had decreasing sPD-L1 levels between baseline and on treatment. Patients with decreasing sPD-L1 levels had significantly longer OS in Cohort #1 (Median OS 15.5 vs 6 months, HR 0.34 95% CI [0.12 – 0.98], p=0.008) and numerically longer OS in Cohorts #2 and #3. In vitro analysis confirmed sPD-L1 secretion by lung cancer cell lines and PBMCs.

Conclusions

sPD-L1 shows prominent biomarker potential and its baseline levels predict response to ICIs in patients with advanced NSCLC treated with ICIs in the first-line setting. The variation of sPD-L1 is also a relevant biomarker.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

A.E. Costantini: Financial Interests, Personal, Advisory Board: BMS. All other authors have declared no conflicts of interest.