158P - XCR1+ dendritic cell (DC) role in antitumoral response to anti PD-L1 antibody: Data from the phase Ib/II trial of DC vaccination in small cell lung cancer patients

Background

The contribution of cross-presenting XCR1+ dendritic cells (DCs) and SIRPα+ DCs in maintaining T cell function in chronic infection has been previously described by our group, but their impact in cancer immunotherapy remains unexplored. We report results from the prespecified translational analysis in VENEZOLUNG trial and preliminary efficacy and safety data.

Methods

VENEZOLUNG is an open-label, phase 1b/2 trial evaluating the safety and efficacy of autologous tumor lysate-pulsed DC product combined with atezolizumab as maintenance therapy in extensive stage small cell lung cancer (ES-SCLC). After standard induction, patients received up to six doses of mature DCs intradermally and atezolizumab 1200 mg iv every three weeks. The dynamic interplay between the DC populations and exhausted CD8+ T cell subsets was analyzed in patient blood samples by flow cytometry to assess markers of T cell exhaustion, effector regulatory T cells, gamma delta T cells, and XCR1+cDC1, exploring correlations with clinical outcomes.

Results

20 patients enrolled, mostly PD-L1 negative (75%) and SCLC-A subtype (58%). Seventeen patients completed DC vaccination (median doses 3, range 1-6). Treatment-related adverse events (TRAEs) occurred in 80% of patients, most grade 1-2. Grade 3-4 TRAEs were chemotherapy related: neutropenia (25%), anemia (15%), thrombocytopenia (10%) and lymphopenia (5%). DC vaccination side effects were grade 1-2 injection site irritation (15%). Overall response was 94%. After a median follow up of 17.4 months (m), median progression free survival was 4.7 m (95% CI, 4.2 to 5.8) and overall survival (OS) 11.6 m (95%CI 6.3, 17.9). PBMCs pre- and post-treatment from 10 patients showed those with expansion of circulating XCR1+ DC (n=6) had a parallel increase in CXCR5+PD-1+ follicular helper CD8 T cells and a median OS of 26 m (95% CI, 6.8, NA) vs 6.3 m (95% CI, 5-12.1) in patients without significant XCR1+ DC expansion (p=0.035). Decrease of Tpex (CXCR5+ PD1+ non-naive CD8+ T cells), cDC1s, cDC2scorrelated with higher risk of death (p-value <0.05).

Conclusions

The role of XCR1+ DCs could be crucial for checkpoint inhibitor-based therapy.

Clinical trial identification

NCT04487756.

Legal entity responsible for the study

Institut Oncologico Dr Rosell (IOR).

Funding

Roche.

Disclosure

M. Gonzalez Cao: Non-Financial Interests, Institutional, Sponsor/Funding: Roche, Regeneron, Astra zeneca, Novartis. All other authors have declared no conflicts of interest.