A Study of MTL-CEBPA in Combination With a PD-1 Inhibitor in Patients With Advanced Solid Tumours (TIMEPOINT)

Summary

This is an open label Phase 1a/1b study in patients who have advanced solid cancer tumours. Patients will receive MTL-CEBPA (an experimental drug) in combination with pembrolizumab (a drug which has been given approval for use for some tumour types). The Phase 1a dose escalation part of the study is designed to establish which doses of MTL-CEBPA are safe and well-tolerated when combined with the standard dose of pembrolizumab. Patients recruited to this part of the study will be those whose cancer progressed on standard treatment(s) or for whom no treatments are available. Phase 1b the dose expansion part of the study will further explore how safe and well-tolerated these two drugs are when combined and will assess if the combination of drugs could potentially reduce the size of tumours. Participants in this part of the study will receive the experimental drug (MTL-CEBPA) at a dose which is considered safe and well-tolerated based on data from the first part of the study (Phase 1a). Participants will remain in the study taking study drugs until either death, or they choose to withdraw from the study.

Timeline

Start

2019-11-13

Primary completion

2025-01-25

Completion

2025-01-25

Publications

• Plummer R, Sodergren MH, Hodgson R, Ryan BM, Raulf N, Nicholls JP, Reebye V, Voutila J, Sinigaglia L, Meyer T, Pinato DJ, Sarker D, Basu B, Blagden S, Cook N, Jeffrey Evans TR, Yachnin J, Chee CE, Li D, El-Khoueiry A, Diab M, Huang KW, Pai M, Spalding D, Talbot T, Noel MS, Keenan B, Mahalingam D, Song MS, Grosso M, Arnaud D, Auguste A, Zacharoulis D, Storkholm J, McNeish I, Habib R, Rossi JJ, Habib NA. TIMEPOINT, a phase 1 study combining MTL-CEBPA with pembrolizumab, supports the immunomodulatory effect of MTL-CEBPA in solid tumors. Cell Rep Med. 2025 Apr 15;6(4):102041. doi: 10.1016/j.xcrm.2025.102041. Epub 2025 Mar 31.
• Hashimoto A, Sarker D, Reebye V, Jarvis S, Sodergren MH, Kossenkov A, Sanseviero E, Raulf N, Vasara J, Andrikakou P, Meyer T, Huang KW, Plummer R, Chee CE, Spalding D, Pai M, Khan S, Pinato DJ, Sharma R, Basu B, Palmer D, Ma YT, Evans J, Habib R, Martirosyan A, Elasri N, Reynaud A, Rossi JJ, Cobbold M, Habib NA, Gabrilovich DI. Upregulation of C/EBPalpha Inhibits Suppressive Activity of Myeloid Cells and Potentiates Antitumor Response in Mice and Patients with Cancer. Clin Cancer Res. 2021 Nov 1;27(21):5961-5978. doi: 10.1158/1078-0432.CCR-21-0986. Epub 2021 Aug 18.

Drugs

Indications