Safety and efficacy of BAL0891 as monotherapy and in combination with paclitaxel: Results from a phase I study in advanced solid tumors.

초록

Background: BAL0891 is a first-in-class dual threonine tyrosine kinase (TTK) and polo-like kinase 1 (PLK1) inhibitor designed to disrupt the spindle assembly checkpoint (SAC), resulting in aberrant mitosis and tumor cell death. We report interim safety, PK/PD, and preliminary antitumor activity from the ongoing first-in-human (FIH) phase I TTK-CS-101 study evaluating BAL0891 as monotherapy (Substudy 1) and in combination with paclitaxel (Substudy 3) in patients with advanced solid tumors. Methods: Patients (pts) with advanced/metastatic solid tumors refractory to or intolerant of standard therapy were enrolled. In this ongoing, multicenter, open-label FIH phase I study, pts received escalating BAL0891 as monotherapy in Substudy 1 Regimen A (RA; D1/D8 Q3W) or Regimen C (RC; D1/D15 Q4W), or in Substudy 3 (BAL0891 D1/D15 plus paclitaxel 60 mg/m² D1/D8/D15 Q4W). The primary objectives were to assess safety/tolerability and to determine MTD/RP2D. Results: As of December 31, 2025, 61 pts received $1doseacross9doselevels(5–280mg):Substudy1RAn=42(24escalation,18backfill),Substudy1RCn=9,andSubstudy3n=10.DLTs(neutropenia,febrileneutropenia,anemia)occurredat160mg(RA),240mg(RA/RC),and280mg(RC);noDLTswerereportedinSubstudy3todate.TheSubstudy1RAMTDwas240mg,andRP2Dwas160mg.Mostpts(88$2 prior metastatic treatment lines. Grade $3treatment-relatedadverseevents(TRAEs)occurredin38pts(62.3$1 post-baseline assessment). Dose escalation is ongoing, and updated results will be presented. Conclusions: BAL0891 demonstrated a tolerable safety profile and consistent systemic exposure in heavily pretreated pts. These interim data support continued clinical evaluation of BAL0891 as monotherapy and in combination with paclitaxel. Clinical trial information: NCT05768932. Research Sponsor: SillaJen Biotherapeutics, Inc.