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631 Pharmacokinetics and pharmacodynamics study of TU2218, TGFβRI and VEGFR2 dual inhibitor in patients with advanced solid tumors
  1. Hyesung Shin1,
  2. Huntaek Kim1,
  3. Soo Jin Kim1,
  4. Eunsun Lee1,
  5. Do-Youn Oh2,
  6. Kyu Pyo Kim3 and
  7. Anthony W Tolcher4
  1. 1TiumBio Co., Ltd, Seongnam, Gyeonggi-do, Republic of Korea
  2. 2Seoul National University Hospital, Seoul, Republic of Korea
  3. 3Asan Medical Center, Seoul, Republic of Korea
  4. 4NEXT Oncology, San Antonio, TX, USA
  • Journal for ImmunoTherapy of Cancer (JITC) preprint. The copyright holder for this preprint are the authors/funders, who have granted JITC permission to display the preprint. All rights reserved. No reuse allowed without permission.


Background TU2218 is a highly potent, oral dual inhibitor against TGFβ type I receptor (TGFβRI/ALK5) and VEGFR2. VEGF and TGF-β pathways play important roles in the function of TME, especially in immune tolerance inextricably related with poor outcomes of anti-PD-(L)1 therapy. This is a first-in-human study to investigate the safety and tolerability of TU2218 mono- and combination therapy with pembrolizumab.

Methods This non-randomized, multinational, open-label study has been evaluating the safety, tolerability, PK, PD and preliminary efficacy of TU2218 mono- and combination therapy with pembrolizumab in advanced solid tumors. The eligible patients were aged ≥ 18 years, ECOG (0 or 1), and had measurable tumors per RECIST 1.1. TU2218 monotherapy was planned at 6 dose levels (30, 60, 105, 150, 195, 270 mg/day) with 2 weeks on and 1 week off in 3-week cycles according to the BOIN method. The starting dose of TU2218 given with pembrolizumab was determined after yielding TRAEs of at least Grade 2 in severity during monotherapy using the traditional 3+3 design.

Results Seventeen patients with advanced solid tumors received 5 different dose levels of monotherapy. Major demographics, treatment-related adverse events (TRAEs) and PK parameters are summarized in table 1.

No TRAEs of Grade 3 or higher were reported while all Grade 2 TRAEs were tolerable in TU2218 monotherapy. Systemic exposure to TU2218 increased over-proportionally with the dose-escalation. TU2218 showed reduction in PD marker of TGFβ, CTGF and PAI-1 after 7 days administration (figure 1) and correlation between TU2218 exposure (AUC) and PD markers of TGFβ and CTGF (P<0.05). 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.

Trial Registration This trial registered in (NCT05204862)

Ethics Approval This study protocol, informed consent and all applicable information had been reviewed and approved by the IRB/ECs of the participating study indtitutions. (Salus IRB: Protocol Number TUC1PI-01, NXSAT21.72; Seoul National Univeraity Hospital Institutional Review Board Protocol Number TUC1PI-01, H-2203–016-1304; Institutional Review Board Asan Medical Center Protocol Number TUC1PI-01, 2022–0395)

Abstract 631 Figure 1

PD Markers of TGFβ, CTGF and PAI-1 After 7 Days Administration of TU2218

Abstract 631 Table 1

Summary of Demographics, TRAE and PK Parameters

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