BAL0891 in Patients With Advanced Solid Tumors or Relapsed or Refractory Acute Myeloid Leukemia

Substudy 1 (monotherapy dose-escalation cohorts) This study will be initiated with enrollment into Substudy 1 and will estimate the safety, tolerability, PK, and PD of increasing doses of BAL0891 in patients with advanced solid tumors. The starting dose will be 5 mg based on the GLP (Good Laboratory Practice) toxicology studies. Dose escalation will comprise a dose range from a dose of 5 mg up to a maximum absolute dose of 480 mg, with eight nominal dose levels (DLs) of 5 / 10 / 20 / 40 / 80 / 160 / 320 / 480 mg. Intra-patient dose escalations are only allowed for patients enrolled in single-patient DL Cohorts 1.1, 1.2, and 1.3. From DL Cohort 1.4 onwards, the projected maximum dose-escalation factor will be two-fold; if the DL cohort investigates an increased dose, dosing of the patients within the cohort must be separated by at least 7 days. For cohorts in which doses are not increased (including backfill enrollment), patients may be enrolled concurrently.

BAL0891 will be administered intravenously (IV) on Day (D) 1 and D8 every 3 weeks (Q3W); for the schedule of assessments of Regimen A. Alternative 21-day or 28-day dosing regimens may be investigated; for the schedule of assessments of Regimens B-D.

Substudies 2 and 3 (dose-escalation cohorts for combination regimens) Enrollment into Substudies 2 and 3 may commence as early as first signs of expected target toxicity and/or efficacy with Regimen A (or an alternative monotherapy regimen) have been observed, or alternatively, once the MTD of BAL0891 monotherapy has been assessed. Patients enrolled into Substudies 2 and 3 will be treated with increasing doses of BAL0891 in combination with tislelizumab or paclitaxel, respectively, and dose escalation of both BAL0891 and tislelizumab/paclitaxel if required will use the same cumulative BLRM-EWOC model as Substudy 1. The starting dose of BAL0891 in combination with tislelizumab or paclitaxel will be a safe DL determined in Substudy 1 but not higher than approximately half the MTD. Backfill enrollment of up to a total of 30 additional patients for both substudies (who may be enrolled concurrently) may be used to better estimate the RP2D for each combination if required.

Substudy 4 (dose escalation cohort for monotherapy in r/r AML) Substudy 4 will evaluate BAL0891 monotherapy in patients with relapsed/refractory AML (r/r AML) using the same BLRM-EWOC model and study design described for Substudy 1. BAL0891 will be administered intravenously on Day 1 and Day 8 every three weeks (Regimen A; see Table 13 for schedule of assessments). Dose exploration will proceed until the highest planned dose level (DL) is determined to be safe and tolerable, or the MTD/RP2D is identified.