1472TiP - Organ preservation with durvalumab-based immunotherapy in combination with chemoradiation as definitive therapy for early stage, cT1 and cT2N0, esophageal adenocarcinoma: A prospective, multicenter study of the FLOT-AIO Gastric Cancer Group – The IKF-057/ PRESTO trial

Background

The outcome of patients (pts) with adenocarcinomas of stomach and esophagogastric junction (GEJ) remains unsatisfactory (5-year survival of 24-84%), whereby surgical resection is considered as cornerstone of the curative treatment for pts with early-stage esophageal adenocarcinoma (EGA), however, it is associated with mortality, morbidity and an impact on quality of life. Investigations showed that in locally advanced EGA benefit could be achieved by combining surgery with neoadjuvant chemoradiotherapy (CROSS trial) or by perioperative treatment with FLOT (FLOT4 trial). Therapy by using checkpoint inhibitors is approved in the palliative and adjuvant EGA situation. In this trial we aim for the organ preservation treatment of EGA pts with the anti PD-L1 antibody durvalumab- FLOT - and chemoradio-therapy.

Trial design

This is a multicenter, single arm, open-label, phase II trial including a total of 32 pts with T1-T2N0 EGA (including GEJ) with indication for radical surgery. Pts will receive durvalumab (1500 mg Q4W) in parallel to 2 cycles FLOT, followed by 3 cycles of mFOLFOX plus concomitant radiation (25 daily fractions with 2.0 Gy = Σ50Gy). 8 weeks after last treatment, pts will undergo tumor assessment by esophagogastroduodenoscopy with biopsies, endoscopic ultrasonography, and CT- or MRI-scans. Pts with complete remission will receive durvalumab monotherapy (1500 mg, Q4W, max. 12 cycles), whereas surgical resection will be offered to pts with locoregional persistence. Primary endpoint is the rate of cCR/pCR at time of re-evaluation. Secondary endpoints include rate of cCR/pCR at 1, 2 and 3 years, rate of salvage surgery, 90 day and 1 year mortality after start of treatment, safety and quality of life. In this exploratory trial a cCR/pCR rate of ≥75% would indicate that the study treatment should be further investigated, whereas a rate < 55% indicates no further investigation. First patient was enrolled on 2023-08-28. Currently seven pts are recruited.

Clinical trial identification

NCT05713838; EudraCT: 2022-001752-42.

Editorial acknowledgement

Legal entity responsible for the study

Frankfurter Institut für Klinische Krebsforschung IKF GmbH.

Funding

AstraZeneca.

Disclosure

T.O. Goetze: Non-Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Bayer, BMS, Daiichi Sankyo, Foundation Medicine, Lilly, MCI, MSD Sharp & Dohme, Novartis, Roche, Sanofi Aventis, Servier, Deciphera, Boehringer Ingelheim; Financial Interests, Personal, Royalties: Amgen, BMS, Lilly, MSD, Novartis, Sanofi Aventis, Servier, Roche, GSK, Lilly; Financial Interests, Personal, Research Funding: AstraZeneca, Incyte, DFG, Gemeinsamer Bundesausschuss, Deutsche Krebshilfe, Servier; Financial Interests, Personal, Other: Amgen, AstraZeneca, BMS, Lilly, Merck Serono, Roche, Sanofi Aventis, Servier, Pierre Fabre. D. Pink: Financial Interests, Institutional, Invited Speaker: Blueprint, PharmaMar, Boehringer Ingelheim, Deciphera; Financial Interests, Institutional, Advisory Board: Roche, PharmaMar, Boehringer Ingelheim; Financial Interests, Institutional, Coordinating PI: BMS, Recordati, PharmaMar, Lilly, Roche, Boehringer Ingelheim; Financial Interests, Institutional, Other, scientific lead of a trial with funding from Novartis: Novartis; Non-Financial Interests, Project Lead: Institut für Klinische Forschung Frankfurt; Non-Financial Interests, Member: ASCO, Deutsche Krebsgesellschaft - German Cancer Society (DKG), Connective Tissue Oncology Society (CTOS), Deutsche Sarkomstiftung (DSS). S. Al-Batran: Financial Interests, Personal, Advisory Board: Lilly, Bristol Myers Squibb, MSD Sharp & Dohme; Financial Interests, Personal, Invited Speaker: MCI Deutschland GmbH; Financial Interests, Personal, Ownership Interest, CEO: Institut für Klinische Krebsforschung IKF GmbH; Financial Interests, Institutional, Research Grant: Sanofi, Roche, Celgene, Lilly, Eurozyto, Immutep, Ipsen, Bristol Myers Squibb, MSD Sharp & Dohme, AstraZeneca, German Cancer Aid (Krebshilfe), German Research Foundation, Federal Ministry of Education and Research. All other authors have declared no conflicts of interest.