Long-term outcomes for patients with limited-disease small cell lung cancer (LD-SCLC) remain poor, with a median survival of 2-years and 5-year survival rates of around 25%, with both distant metastases and local recurrence remaining problematic after concurrent chemoradiotherapy and prophylactic cranial irradiation (PCI). In a phase II trial immune-checkpoint blockade combining ipilimumab with nivolumab for the treatment of recurrent SCLC has shown promising efficacy signals with an overall response rate of 33% in heavily pre-treated SCLC, with durable responses and an acceptable toxicity profile. Consolidation therapy using the PD-L1 antibody durvalumab demonstrated improved progression free and overall survival in non-small cell lung cancer (NSCLC) following concurrent chemoradiotherapy. Consolidation therapy using nivolumab in combination with ipilimumab may improve survival outcomes for LD-SCLC.
This international, open-label randomised phase 2 trial will enrol 325 patients with newly diagnosed LD-SCLC and aims to randomise 260 patients. Upon completion of platinum etoposide chemotherapy, concurrent thoracic radiotherapy then PCI, patients without disease progression will be randomised 1:1 to receive consolidation with nivolumab (1mg/kg) and ipilimumab (3mg/kg IV q3 weeks for 4 cycles) followed by nivolumab (240mg IV q2 weeks for up to 12 months), or observation alone. Major trial endpoints include overall survival (OS) and progression-free survival (PFS) (co-primary), objective response, time to treatment failure, and adverse events. Imaging will be performed every 9 weeks until 18 months, then every 12 weeks until 2 years, every 6 months until 4 years, and at 5 years.
STATUS (as of 8 Aug 2018): In Australia, HREC approval received, sites preparing for site activation. Australia to recruit 50 patients from 25 sites. Internationally, 192 patients enrolled/112 randomised.
STIMULI is a cooperative group trial sponsored by the ETOP and coordinated in collaboration with the ALTG and NHMRC CTC, University of Sydney with support from Bristol Myers Squibb.