Debio 1143-201 Dose-finding and Efficacy Phase I/II Trial

Summary

The use of multiple drugs in a single clinical trial or as a therapeutic strategy has become common, particularly in the treatment of cancer. Because traditional trials are designed to evaluate one agent at a time, the evaluation of therapies in combination requires specialized trial designs. In place of the traditional separate phase I and II trials, this trial uses a single phase I/II clinical trial to evaluate simultaneously the safety and efficacy of combination dose levels, and select the optimal combination dose. Therefore, this is a two part trial of Debio 1143 combined with concurrent cisplatin and radiotherapy (CRT) in participants with previously untreated stage III, IVa or IVb head and neck cancer. The trial begins with an initial period of dose escalation (Phase I) to investigate the maximum tolerated dose (MTD) of Debio 1143 that can safely be given in combination with CRT. Using the MTD determined in the Phase I portion, the randomized phase II trial in 94 participants compares Debio 1143 to placebo, both with concomitant CRT. The aim is to evaluate the efficacy and safety of Debio 1143.

Timeline

Start

2013-10

Primary completion

2020-07

Completion

2022-04-28

Publications

• Vugmeyster Y, Ravula A, Rouits E, Diderichsen PM, Kleijn HJ, Koenig A, Wang X, Schroeder A, Goteti K, Venkatakrishnan K. Model-Informed Selection of the Recommended Phase III Dose of the Inhibitor of Apoptosis Protein Inhibitor, Xevinapant, in Combination with Cisplatin and Concurrent Radiotherapy in Patients with Locally Advanced Squamous Cell Carcinoma of the Head and Neck. Clin Pharmacol Ther. 2024 Jan;115(1):52-61. doi: 10.1002/cpt.3065. Epub 2023 Oct 23.
• Tao Y, Sun XS, Pointreau Y, Tourneau CL, Sire C, Gollmer K, Crompton P, Bourhis J. Long-term results from a clinical study of xevinapant plus chemoradiotherapy in people with high-risk locally advanced squamous cell carcinoma of the head and neck: a plain language summary. Future Oncol. 2023 Aug;19(26):1769-1776. doi: 10.2217/fon-2023-0322. Epub 2023 Jul 13.
• Tao Y, Sun XS, Pointreau Y, Le Tourneau C, Sire C, Kaminsky MC, Coutte A, Alfonsi M, Calderon B, Boisselier P, Martin L, Miroir J, Ramee JF, Delord JP, Clatot F, Rolland F, Villa J, Magne N, Elicin O, Gherga E, Nguyen F, Lafond C, Bera G, Calugaru V, Geoffrois L, Chauffert B, Damstrup L, Crompton P, Ennaji A, Gollmer K, Nauwelaerts H, Bourhis J. Extended follow-up of a phase 2 trial of xevinapant plus chemoradiotherapy in high-risk locally advanced squamous cell carcinoma of the head and neck: a randomised clinical trial. Eur J Cancer. 2023 Apr;183:24-37. doi: 10.1016/j.ejca.2022.12.015. Epub 2023 Jan 9.
• Sun XS, Tao Y, Le Tourneau C, Pointreau Y, Sire C, Kaminsky MC, Coutte A, Alfonsi M, Boisselier P, Martin L, Miroir J, Ramee JF, Delord JP, Clatot F, Rolland F, Villa J, Magne N, Elicin O, Gherga E, Nguyen F, Lafond C, Bera G, Calugaru V, Geoffrois L, Chauffert B, Zubel A, Zanna C, Brienza S, Crompton P, Rouits E, Gollmer K, Szyldergemajn S, Bourhis J. Debio 1143 and high-dose cisplatin chemoradiotherapy in high-risk locoregionally advanced squamous cell carcinoma of the head and neck: a double-blind, multicentre, randomised, phase 2 study. Lancet Oncol. 2020 Sep;21(9):1173-1187. doi: 10.1016/S1470-2045(20)30327-2. Epub 2020 Aug 3.

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Indications