NCE 401

The starting dose of TU2218 in combination with pembrolizumab was 105mg/day, with subsequent incremental doses of 150mg/day and 195mg/day. Conclusions TU2218, a first-in-class oral dual inhibitor against TGFβRI and VEGFR2, was well-tolerated in the monotherapy and will be subsequently investigated for the combination therapy with PD-L1.

This is a first-in-human study to investigate the safety and tolerability of TU2218 mono- and combination therapy with pembrolizumab. To date, clinical studies of TU2218 are ongoing. Conclusions TU2218, a first-in-class oral dual inhibitor against TGFβRI and VEGFR2, was well-tolerated in the monotherapy.

P1b/2a, N=142, Recruiting, TiumBio Co., Ltd. | Trial completion date: May 2024 --> Dec 2028 | Trial primary completion date: Dec 2023 --> Dec 2026

The restored level of ICAM-1 and VCAM-1 at 1 μM TU2218 was equivalent to the activity of combined treatment of 1 μM Vactosertib (ALK5 inhibitor) and 25 μg/ml Ramucirumab (VEGFR2 inhibitor). We conclude that TU2218 leads not only to the enhancement of T cell-traffic toward TME, but also to the conversion of immune balance favorable to anti-PD1 therapy. The Phase 1b trial of TU2218 combined with pembrolizumab is underway for advanced solid cancers (NCT05204862).