A Platform Study of Novel Agents in Combination With Radiotherapy in NSCLC
Summary
CONCORDE is a multi-institution, multi-arm, Phase IB study that will determine the recommended phase II dose (RP2D) and safety profiles of different DNA damage repair inhibitors (DDRis) when given in an open label fashion in combination with fixed dose curative intent radiotherapy (RT) in patients with stage IIB/IIIA/IIIB NSCLC, followed by up to 12 months of consolidation durvalumab immunotherapy in selected study arms. The RP2D will be evaluated by incorporating the number of observed dose limiting toxicities (DLTs) into a time to event continuous reassessment method (TiTE- CRM) model within each of the experimental arms. TiTE-CRM is used here to take into account longer-term toxicities up to 13.5 months post start of radiotherapy and use these to inform dose escalation decision making.
Timeline
- Start
- 2021-03-17
- Primary completion
- 2026-03
- Completion
- 2028-03
Publications
- Background Faivre-Finn C, Brown S, Ryan A, Greystoke A; CONCORDE Investigators. The UK at the Forefront of Innovative Drug-Radiotherapy Combination Clinical Trials: Introducing the CONCORDE Platform. Clin Oncol (R Coll Radiol). 2020 Jun;32(6):358-362. doi: 10.1016/j.clon.2020.02.003. Epub 2020 Feb 24. No abstract available.
- Background Walls GM, Oughton JB, Chalmers AJ, Brown S, Collinson F, Forster MD, Franks KN, Gilbert A, Hanna GG, Hannaway N, Harrow S, Haswell T, Hiley CT, Hinsley S, Krebs M, Murden G, Phillip R, Ryan AJ, Salem A, Sebag-Montefoire D, Shaw P, Twelves CJ, Walker K, Young RJ, Faivre-Finn C, Greystoke A. CONCORDE: A phase I platform study of novel agents in combination with conventional radiotherapy in non-small-cell lung cancer. Clin Transl Radiat Oncol. 2020 Sep 22;25:61-66. doi: 10.1016/j.ctro.2020.09.006. eCollection 2020 Nov.
- Walker K, Hinsley S, Phillip R, Oughton JB, Murden G, Chalmers AJ, Faivre-Finn C, Greystoke A, Brown SR; CONCORDE Investigators. Implementation of the Time-to-Event Continuous Reassessment Method Design in a Phase I Platform Trial Testing Novel Radiotherapy-Drug Combinations-CONCORDE. JCO Precis Oncol. 2022 Nov;6:e2200133. doi: 10.1200/PO.22.00133.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | AZD1390 | Small molecule | — | Oral |
| Subject | Ceralasertib | Small molecule | — | Oral |
| Subject | Durvalumab | Monoclonal antibody | 1500 mg | Intravenous |
| Subject | Olaparib | Small molecule | — | Oral |
| Subject | Saruparib | Small molecule | — | Oral |