BAL0891 (dual TTK/PLK1 spindle-checkpoint inhibitor) sets 160 mg RP2D with early disease control in refractory solid tumors

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) and drive mitotic catastrophe; in the ongoing, multicenter, open-label first-in-human Phase I TTK-CS-101 dose-escalation study (NCT05768932), it was tested as monotherapy (D1/D8 Q3W or D1/D15 Q4W) and with paclitaxel 60 mg/m² (D1/D8/D15 Q4W) in advanced/metastatic solid tumors after standard therapy (61 treated; 88% with ≥2 prior metastatic lines). DLTs were mainly myelosuppression (neutropenia/febrile neutropenia/anemia) at higher doses; Substudy 1 (D1/D8 Q3W) established MTD 240 mg and RP2D 160 mg, with Grade ≥3 TRAEs in 62.3% overall (most commonly neutropenia), while no DLTs were reported yet in the paclitaxel-combination substudy (n=10) as of December 31, 2025. Among efficacy-evaluable patients in the table (monotherapy D1/D8: n=23; monotherapy D1/D15: n=8; combo: n=8), ORR was 0%, 25%, and 38% respectively, with DCR 70%, 63%, and 88%—roughly in the “disease-control-first” range you often see with early-phase cytostatic or schedule-sensitive mitotic agents in unselected, heavily pretreated pan-tumor populations (and notably, the combo ORR is within the broad ballpark reported for single-agent weekly paclitaxel across multiple tumor types, so separation from paclitaxel alone will matter in future expansion).