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

Abstract

e15160 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 ≥1 dose across 9 dose levels (5–280 mg): Substudy 1 RA n = 42 (24 escalation, 18 backfill), Substudy 1 RC n = 9, and Substudy 3 n = 10. DLTs (neutropenia, febrile neutropenia, anemia) occurred at 160 mg (RA), 240 mg (RA/RC), and 280 mg (RC); no DLTs were reported in Substudy 3 to date. The Substudy 1 RA MTD was 240 mg, and RP2D was 160 mg. Most pts (88%) had ≥2 prior metastatic treatment lines. Grade ≥3 treatment-related adverse events (TRAEs) occurred in 38 pts (62.3%); the most common TRAEs were neutropenia (n = 41), fatigue (G1/2; n = 17), and leukopenia (n = 15). PK in Substudy 1 RA showed predictable exposure with minimal inter-occasion variability. Thirty-nine pts were efficacy-evaluable (≥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 . Best overall response and clinical outcomes. Substudy 1 (D1/D8 Q3W) Substudy 1 (D1/D15 Q4W) Substudy 3 (Paclitaxel Combination) N 23 8 8 Median prior treatment lines (range) 3 (1–5) 3 (1–6) 2 (1–5) Best overall response CR 0 1 0 PR 0 1 3 SD 16 4 4 PD 7 3 1 DCR, % (95% CI) 70 (47–87) 63 (25–92) 88 (47–100) CBR, % (95% CI) 52 (31–73) 25 (3–65) 63 (25–92) ORR, % (95% CI) 0.00 (0.00–15) 25 (7–53) 38 (9–76)