This trial is an open-label, randomized, 3-stage, phase 2 study. Patients who have failed ≥2 prior chemotherapy regimens (including high-dose chemotherapy) will be randomized to receive one of the following: Durvalumab, 1.5 g via IV infusion every 4 weeks, for up to a total of 12 months (13 doses/cycles) alone or with Tremelimumab, 75 mg IV every 4 weeks, starting on week 0, for up to 4 months (4 doses/cycles).
Serum tumor markers, computed tomography and FDG-PET scans will be repeated every 8 weeks. The primary endpoint is the objective response-rate (ORR= complete response or partial response with normal markers). The null hypothesis is: ORR rate ≤10%, while H1: ORR ≥25%, with type I and II error defined at 10%.
In stage 1, 11 patients will be allocated in each arm. According to Gehan’s rule, the trial will be terminated whenever no response will be observed. In stage 2 - 29 additional patients will be added to each arm fulfilling stage 1 criteria. ORR in ≥7 pts will be required. In stage 3, patients from stage 1-2 of both arms will be retrospectively evaluated for PDL 1 IHC. 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.
The trial has started recruiting patients on February 2017 and is expected to recruit the last patient in February 2020.
Presented by: Necchi A., Mariani L., Anichini A., Giannatempo P., Raggi D., Togliardi E, Calareso G., Nicolai N., Crippa F., Salvioni R.
Written by: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto
at the #EAU17 -March 24-28, 2017- London, England