CONCORDE: a phase Ib platform study of novel agents in combination with conventional radiotherapy in non-small cell lung cancer (NSCLC)

Abstract

Introduction: The CONCORDE study is sponsored by the University of Leeds and funded by Cancer Research UK and AstraZeneca. It is an innovative, hypothesis-driven open-label, randomised, phase Ib, multi-institution, platform study for patients with NSCLC receiving radical radiotherapy (RT). It aims to assess five DNA damage response inhibitors (DDRi) with participants randomised to receive one agent in combination with RT or RT alone. Two of the arms will also deliver Durvalumab and DDRi consolidation. CONCORDE adopts a Bayesian adaptive model-based approach to dose escalation. An estimated 210 patients will be recruited from 13 centres across the UK, including 30 patients in each experimental arm and approximately RT alone 50-60. The estimated total duration of trial: 6 years. Methods: Key eligibility: Stage IIB/IIIA/B/C NSCLC, medically inoperable and not suitable for concurrent chemoradiotherapy, ECOG PS 0-1. Patients will be treated with radical RT given at a dose of 60Gy/30# delivered over 6 weeks. As per Fig. 1, they will be allocated to one of 5 study arms as per prioritisation schedule (n=40 per arm). Within that arm they will be randomised to RT with or without DDRi (randomised 3:1). The primary endpoint is to assess the safety and determine the recommend phase II dose (RP2D) of each DDRi. The RP2D will be the dose level at which it is estimated 25% of subjects will experience dose limiting toxicity during and up to 13.5 months following RT Results: Trial arms A (PARPi) and B (ATMi) are open to recruitment in 5 centres and 12 patients have been recruited. Conclusion: Further arms and centres to open soon. Correlative studies aiming to identify biomarkers of toxicity and response to combination therapy, and the impact of treatment on the immune system are in development. For further information go to: https:// clinicaltrials.gov/ct2/show/NCT04550104 Trials unit contact: ctru_ concorde@leeds.ac.uk.