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

Background

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.

Methods

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.

Results

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.

Conclusions

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.

Clinical trial identification

NCT03568097.

Legal entity responsible for the study

Hellenic Co-operative Oncology Group.

Funding

The study was financially supported by Merck (CrossRef Funder ID: 10.13039/100009945).

Disclosure

G. Mountzios: Financial Interests, Personal, Advisory Board: Roche, BMS, Takeda, Janssen; Financial Interests, Personal, Invited Speaker:MSD, AstraZeneca, Pfizer, Novartis, Amgen. E. Samantas: Financial Interests, Personal, Advisory Board: Merck, Genesis, Amgen, Roche, AstraZeneca, MSD Hellas. G. Aravantinos: Financial Interests, Personal, Advisory Board: Pfizer, Merck, Genesis Pharma, Amgen, Novartis, Sanofi, AstraZeneca, Roche, BMS. A.N. Christopoulou: Financial Interests, Personal, Advisory Board: AstraZeneca, Roche, MSD, BMS, Sanofi, Amgen, Pfizer, Novartis. N. Spathas: Financial Interests, Personal, Invited Speaker: Roche, BMS, AstraZeneca; Financial Interests, Personal, Advisory Role: Sanofi, Amgen, Roche. E. Fountzilas: Financial Interests, Personal, Advisory Role: Amgen LEO Pharma; Financial Interests, Personal, Invited Speaker: Roche, Pfizer, AstraZeneca, Amgen; Financial Interests, Personal, Other, Travel Grants: AstraZeneca, Merck, Pfizer and DEMO; Financial Interests, Personal, Stocks/Shares: Genprex Inc., Deciphera Pharmaceuticals Inc. A. Psyrri: Financial Interests, Personal, Invited Speaker:MSD, Merck Serono, AstraZeneca, Kura Oncology; Financial Interests, Personal, Advisory Board: Pfizer, Sanofi, MSD, AstraZeneca, BMS, Leo, Rakuten, eTheRNA immunotherapies, Merck Serono; Financial Interests, Personal and Institutional, Invited Speaker: AstraZeneca, Iovance, Pfizer, Roche, GSK, Genesis, Incyte, Amgen, Debiopharm, MSD, Jannsen, Lilly, Regeneron, Sanofi, BI, Roche, Peregrine, Oncolytics Biotech; Financial Interests, Institutional, Invited Speaker: Kura Oncology, Novartis, Replimmune; Financial Interests, Personal And Institutional, Funding: Kura Oncology, BMS, Roche, Demo, Amgen, BI, Genesis, BMS, Pfizer, Oncolytics Biotech; Financial Interests, Institutional, Funding: Merck Serono, Pfizer; Financial Interests, Personal, Other, Educational activity: Medscape, PrimeOncology; Non-Financial Interests, Personal, Project Lead, Medical Education with honoraria: Medscape. A. Koumarianou: Financial Interests, Institutional, Research Grant: Merck. D. Bafaloukos: Financial Interests, Personal, Invited Speaker: Novartis, Pfizer, Merck, Roche, BMS, MSD, Genesis, and Ipsen; Financial Interests, Personal, Advisory Board: Novartis, Pfizer, Merck, Roche, BMS, MSD, Genesis, and Ipsen. P.A. Kosmidis: Financial Interests, Personal, Advisory Board:MSD; Financial Interests, Personal, Other, Registration in Congress: Pfizer; Financial Interests, Personal, Other, Registration to Congress: Sanofi; Financial Interests, Personal, Ownership Interest: Care Across Digital Health Company. G. Fountzilas: Financial Interests, Personal, Advisory Board: Pfizer, Novartis; Financial Interests, Personal, Invited Speaker: AstraZeneca, Novartis; Financial Interests, Personal, Stocks/Shares: Genprex, Daiichi Sankyo, RFL Holdings, Formycon. H. Linardou: Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, MSD, Merck, Takeda, Bristol Myers Squibb, Lilly, Pfizer, GSK; Financial Interests, Personal, Invited Speaker: Roche, AstraZeneca, MSD, Bristol Myers Squibb, Pfizer, Amgen, Novartis; Financial Interests, Personal, Stocks/Shares: BioPath Innovations S.A.; Financial Interests, Personal and Institutional, Invited Speaker: Bristol Myers Squibb, Boehringer Ingelheim, Roche, AbbVie, Lilly, Novartis, AstraZeneca, Amgen, PPD, Parexel ILR, Qualitis, Health Data Specialist; Financial Interests, Institutional, Invited Speaker: GSK; Non-Financial Interests, Personal, Principal Investigator: Hellenic Cooperative Oncology Group; Non-Financial Interests, Personal, Leadership Role, Elected Chair of the Scientific Committee: Hellenic Cooperative Oncology Group; Non-Financial Interests, Personal, Member of Board of Directors: Women 4 Oncology - Hellas, Fairlife Lung Cancer Care, Hellenic Cooperative Oncology Group, Hellenic Foundation for Cancer Research; Non-Financial Interests, Personal, Leadership Role, Legal Representattive: Women 4 Oncology- Hellas. All other authors have declared no conflicts of interest.