197MO Final outcome, immunophenotypic and biomarker analysis of intercalated avelumab plus platinum-based chemotherapy in patients with extensive-stage small cell lung cancer (PAVE): A pilot phase II study of the Hellenic co-operative oncology group

Extensive stage small cell lung cancer (ES-SCLC) is a poor prognosis disease, and first-line chemo-immunotherapy is now the standard-of-care. We hypothesized that intercalated administration of immunotherapy after two induction chemotherapy cycles, at maximal neoantigen release, might enhance immune response and overall efficacy. PAVE is a single-arm, multicenter phase II study of the anti-PD-L1 antibody avelumab combined with platinum-etoposide. A safety run-in preceded the phase II part, where patients with untreated ES-SCLC received standard chemotherapy every three weeks for 4-6 cycles. Avelumab 10 mg/kg was administered every two weeks from cycle 3 until chemotherapy completion, and as maintenance thereafter. The primary endpoint was one-year PFS. Genotyping of FFPE tumors via targeted NGS, assessment of tumor-infiltrating lymphocytes (TILs) density, and analysis of CD8 and PD-L1, was performed. From September 2018 through September 2020, 55 pts, median age 65.9 years, male 67.3% were enrolled. Metastatic sites included liver (54.5%), bone (32.7%), brain (10.9%). With median f-up 10.3 months (m), 1-year PFS was 12.7%, median PFS 5.8 m, 1-year OS 38.2%, median OS 10.3 m. Among ITT pts, ORR was 69.1% (CR 5.5%, PR 63.6%) with median DOR 5.6 m. AEs grade 3-4 occurred in 56% of patients. QoL, global health status and disease-related symptoms were significantly improved. The presence of TILs/CD8 in the tumour did not have any predictive nor prognostic value. All but one tumor carried genetic alterations, with TP53 (89.5%), RB1 (57.9%), NOTCH (31.6%), and MYC (23.7%) the most frequently altered genes. Presence of liver metastases, identification of RB1 or TP53/RB1 co-mutations, no PCI and older age (>65 years) were negative prognosticators for PFS and OS. Intercalated avelumab administration with platinum-etoposide did not meet the primary endpoint of 1-year PFS. However, our results suggest that this approach has comparable efficacy to published frontline chemo-immunotherapy regimens, with clinically relevant PFS, DoR and improved QoL and merits evaluation.