Durvalumab Alone or With Tremelimumab in Refractory Germ Cell Tumors
Status:
Terminated
Trial end date:
2019-12-06
Target enrollment:
Participant gender:
Summary
Background:
The prognosis of pts who have failed multiple chemotherapy (CT) regimens is quite dismal.
PD-L1 is frequently expressed by immunohistochemistry (IHC) in germ cell tumors (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. The investigators 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 fluorodeoxyglucose positron emission tomography (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 Programmed cell Death Ligand-1(PD-L1)
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<30%) or
promising (PP ≥30%). The promising one will enter the stage 3. Should both arms be judged
promising, the one yielding ≥20% PP advantage will be selected; monotherapy will be preferred
otherwise. Details on the algorithm to be used for PD-L1 IHC in this study will be finalized
(EudraCT number 2016-001688-35).
Phase:
Phase 2
Details
Lead Sponsor:
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano