Thiopurine Enhanced Mutations for PD-1/Ligand-1 Efficacy

Summary

The TEMPLE study is a single-center prospective phase Ib and II trial to determine the safety, tolerability and efficacy of Atezolizumab given in combination with thiopurine therapy (6-mercaptopurine and 6-thioguanine) in patients with advanced and/or metastatic solid tumors with an intermediate tumor mutational burden. Maximum tolerated dose (MTD) and/or recommended phase II dose (RP2D) will be determined in a single armed, open label phase Ib trial with a fixed dose of Atezolizumab in combination with thiopurine therapy with a dose-limiting toxicity (DLT) period of 4 weeks. A total of 27-39 patients will be enrolled in the TEMPLE study. Phase Ib will enroll 3-18 patients depending on the number of DLTs and need for dose de-escalation. Data from patients treated in the phase Ib study at RP2D will be included when assessing endpoints in the phase II part of the study. Phase II will enroll a total of 27 patients (including 3-6 patients treated at RP2D in the phase I part of the trial) in a Simon's 2 stage design (13 in stage 1 and 14 in stage 2).

Timeline

Start

2022-09-01

Primary completion

2024-12-31

Completion

2025-09-01

Publications

• Nazerai L, Willis SC, Yankilevich P, Di Leo L, Bosisio FM, Frias A, Bertolotto C, Nersting J, Thastrup M, Buus S, Thomsen AR, Nielsen M, Rohrberg KS, Schmiegelow K, De Zio D. Thiopurine 6TG treatment increases tumor immunogenicity and response to immune checkpoint blockade. Oncoimmunology. 2022 Dec 17;12(1):2158610. doi: 10.1080/2162402X.2022.2158610. eCollection 2023.

Drugs

Indications