STIMULI: A randomised open-label phase II trial of consolidation with nivolumab and ipilimumab in limited-stage SCLC after standard of care chemo-radiotherapy conducted by ETOP and IFCT

Abstract

Background: Preliminary results from trial CheckMate 032, targeting two distinct inhibitory immune checkpoints combining nivolumab, an anti‐PD1 IgG1 monoclonal antibody and ipilimumab, an anti‐CTLA4 IgG1 monoclonal antibody, demonstrate very promising 31% objective response rate (ORR) and 48% one‐year overall survival (OS) in pre‐treated advanced SCLC. This treatment option will be explored in a consolidation setting after curative‐intent chemotherapy, chest radiotherapy (RT) and prophylactic cranial irradiation (PCI) for LD‐SCLC. Trial design: STIMULI is an open‐label, randomised, two‐arm, phase II clinical trial. Inclusion is restricted to stage I‐IIIB untreated LD‐SCLC patients ( pts) with adequate organ and pulmonary function, and no history of auto‐immune disease. Hyper‐ or conventionally fractionated chest RT is administered concomitantly to 4 cycles of Cis‐/ carboplatin plus etoposide, followed by PCI. After completion of this standard treatment, non‐progressing pts are randomised 1:1 to consolidation (induction and maintenance) or observation. Induction consists of four 3‐week cycles of ipilimumab 3mg/kg plus nivolumab 1mg/kg, and is followed by maximally 12 months of nivolumab 240mg every 2 weeks. OS and progression‐free survival (PFS) are co‐primary endpoints. ORR, time to treatment failure and tolerability are secondary endpoints. A total of 325 pts are expected to be enrolled in the standard treatment phase, in order for 260 pts to be randomised, with a target hazard ratio of .70 for OS and .57 for PFS. The overall one‐sided significance level of .05 is split to .04 for OS and .01 for PFS, with power 78% for OS and 80% for PFS. A safety evaluation for pneumonitis will take place after the first 30 patients reach the 12 weeks follow‐up on the experimental arm. Safety will be monitored by the Independent Data Monitoring Committee every 3 months. Translational research will be done on formalin‐fixed, paraffin‐embedded tumour tissue, PBMCs, whole blood and serum samples at the Centre Hospitalier Universitaire Vaudois in Lausanne, Switzerland. Up to April 2016, 7 pts have been randomised, and enrolment is ongoing.