CONCORDE: a phase Ib platform study of novel agents in combination with conventional radiotherapy in non-small cell lung cancer (NSCLC)
Horne, Ashley Ali, A. Brown, S. Butterworth, K. Chalmers, A. Clipson, Alexandra Collinson, F. Forster, M.
Horne, Ashley
Ali, A.
Brown, S.
Butterworth, K.
Chalmers, A.
Clipson, Alexandra
Collinson, F.
Forster, M.
Citations
Altmetric:
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.
Authors
Horne, Ashley
Ali, A.
Brown, S.
Butterworth, K.
Chalmers, A.
Clipson, Alexandra
Collinson, F.
Dive, Caroline
Faivre-Finn, Corinne
Forster, M.
Franks, K.
Gilbert, A.
Hanna, G.
Hannaway, N.
Harrow, S.
Hartley, J.
Hiley, C.
Jones, R.
Kendall, J.
Krebs, Matthew G
Mallison, G.
O'Connor, James P B
Oughton, J.
Phillip, R.
Rothwell, Dominic G
Salem, Ahmed
Sebag-Montefiore, D.
Shaw, P.
Walls, G.
Young, R.
Greystoke, A.
Ali, A.
Brown, S.
Butterworth, K.
Chalmers, A.
Clipson, Alexandra
Collinson, F.
Dive, Caroline
Faivre-Finn, Corinne
Forster, M.
Franks, K.
Gilbert, A.
Hanna, G.
Hannaway, N.
Harrow, S.
Hartley, J.
Hiley, C.
Jones, R.
Kendall, J.
Krebs, Matthew G
Mallison, G.
O'Connor, James P B
Oughton, J.
Phillip, R.
Rothwell, Dominic G
Salem, Ahmed
Sebag-Montefiore, D.
Shaw, P.
Walls, G.
Young, R.
Greystoke, A.
Affiliation
Description
Date
2022
Publisher
Collections
Keywords
Type
Meetings and Proceedings
Citation
Horne A, Ali A, Brown S, Butterworth K, Chalmers A, Clipson A, et al. CONCORDE: a phase Ib platform study of novel agents in combination with conventional radiotherapy in non-small cell lung cancer (NSCLC). Vol. 165, Lung Cancer. Elsevier BV; 2022. p. S69–70.