846TiP - APACHE: An open label, randomized, phase 2 study of the anti-programmed death-ligand 1 (PD-L1) durvalumab (D, MEDI4736), alone or in combination wi...

Date 09 October 2016
Event ESMO 2016 Congress
Session Poster display
Topics Germ Cell Tumours
Presenter Andrea Necchi
Citation Annals of Oncology (2016) 27 (6): 266-295. 10.1093/annonc/mdw373
Authors A. Necchi1, L. Mariani2, A. Anichini3, P. Giannatempo1, D. Raggi1, E. Togliardi4, G. Calareso5, N. Di Genova1, F. Crippa6, R. Salvioni7
  • 1Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 - Milan/IT
  • 2Clinical Epidemiology And Trials Organization Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 - Milan/IT
  • 3Experimental Oncology And Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 - Milan/IT
  • 4Pharmacy Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 - Milan/IT
  • 5Radiology, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 - Milan/IT
  • 6Nuclear Medicine And Pet Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 - Milan/IT
  • 7Surgical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 - Milan/IT

Abstract

Background

The prognosis of pts who have failed multiple chemotherapy (CT) regimens is quite dismal. PD-L1 is frequently expressed by immunohistochemistry (IHC) in GCT. D is a monoclonal antibody (mAb) that inhibits the binding of PD-L1. T, an anti-CTLA4 mAb, is an immunomodulatory therapy. Combination immunotherapy has shown improved activity compared to monotherapy. We aimed to investigate the activity of D, alone or in combination with T, in chemorefractory GCT.

Trial design

This is an open-label, randomized, 3-stage, phase 2 study. Pts who have failed ≥2 prior CT regimens (including high-dose CT) will be randomized to receive one of the following: D, 1.5 g via IV infusion q4w, for up to a total of 12 months (13 doses/cycles) alone or with T, 75 mg IV q4w, starting on week 0, for up to 4 months (4 doses/cycles). Serum tumor markers, computed tomography and FDG-PET scans will be repeated q8 weeks. The primary endpoint is the objective response-rate (ORR = complete response or partial response with normal markers). H0: ORR rate ≤10%, H1: ORR ≥25%, type I and II error rates at 10%. In stage 1, 11 pts will be allocated in each arm. According to Gehan's rule, the trial will be terminated whenever no response will be observed. 29 additional pts will be added to each arm fulfilling stage 1 criteria. ORR in ≥7 pts will be required. In stage 3, pts from stage 1-2 of both arms will be retrospectively evaluated for PDL-1 IHC. The Ventana PD-L1 IHC assay will be used. In case of negative findings at the end of stage 2, if the target benefit is likely to occur only in PD-L1+ pts, further study prosecution in accordance with an enrichment strategy will be undertaken. In particular, predictive power (PP) will be calculated assuming expansion of PD-L1+ cohorts up to a maximum of 60 pts. Each arm will be categorized as not-promising (PP 

Clinical trial identification

EudraCT 2016-001688-35

Legal entity responsible for the study

Fondazione IRCCS Istituto Nazionale dei Tumori

Funding

AstraZeneca

Disclosure

All authors have declared no conflicts of interest.