Title
A Phase 1/1b Open-Label, Dose Escalation, First-in-Human Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Anti-leukemic Activity of the Orally Available CDC-Like Kinase (CLK) Inhibitor, BH-30236, in Adults with Relapsed or Refractory Acute Myelogenous Leukemia (R/R AML) or Higher-Risk Myelodysplastic Syndrome (HR-MDS)

Description
Study BH-30236-01 is a first-in-human (FIH), Phase 1/1b, open-label, dose escalation and expansion study in participants with relapsed/refractory acute myelogenous leukemia (R/R AML) or higher-risk myelodysplastic syndrome (HR-MDS).

Phase 1 (Dose Escalation) will evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy of BH-30236 administered orally. Approximately 50 participants may be enrolled in Phase 1 of the study.

Phase 1b (Dose Expansion) will follow Phase 1 to further understand the relationships among dose, exposure, toxicity, tolerability, and clinical activity. Up to 24 participants may be enrolled in Phase 1b of the study.

The dose expansion part (Phase 1b) will be followed to understand the relationships among dose, exposure, toxicity, tolerability and clinical activity. Up to 24 participants may be enrolled in Phase 1b of the study.

Objective
Primary:
Dose Esclation:
-To evaluate the safety and tolerability of BH-30236 in adult subjects with R/R AML or HR-MDS and determine the maximum tolerated dose (MTD)
-To identify the recommended doses for expansion (RDEs)
Dose Expansion:
-To evaluate the safety, tolerability, and preliminary anti-leukemic activity of BH-30236 at selected RDEs to determine the recommended Phase 2 dose (RP2D)

Treatment This is a Phase 1/1b, multi-center, open-label, dose escalation, first-in-human study to evaluate the safety, tolerability, PK, PD, and preliminary anti-leukemic activity of the CLK inhibitor, BH-30236, in adult subjects with R/R AML or HR-MDS.

The study consists of two parts: Phase 1 Dose Escalation and Phase 1b Dose Expansion.

Phase 1 Dose Escalation is anticipated to enroll approximately 50 subjects to evaluate the safety, tolerability, PK, PD, and preliminary anti-leukemic activity of BH-30236, as well as determine the MTD and/or the preliminary recommended dose(s) for expansion (RDEs).

Phase 1 will follow an accelerated 3 + 3 dose escalation, where participants will receive ascending doses of BH-30236 to determine the recommended RDEs.

Phase 1b Dose Expansion will enroll approximately 24 subjects to evaluate the safety, tolerability, and preliminary anti-leukemic activity of BH-30236 at selected RDEs determined in Phase 1 Dose Escalation.

Key Eligibility Inclusion criteria:

>/=18 years.

Diagnosis of relapsed/refractory acute myelogenous leukemia (R/R) AML or higher-risk myelodysplastic syndrome (HR-MDS) with ≥5% bone marrow blast at time of inclusion.

Prior treatment history must include 1-5 prior lines of therapy.

ECOG performance status
Adequate organ function evidenced by the following laboratory values:

Hepatic: Transaminase levels aspartate aminotransferase [AST]/ alanine transaminase [ALT]
Renal: Measured or calculated creatinine clearance >/= 60 mL/min (Cockcroft-Gault formula)

The above are a summary, other inclusion criteria details may apply.

Diagnosis of acute promyelocytic leukemia or chronic myeloid leukemia with blast crisis.

Prior allogeneic HSCT within 3 months or donor lymphocyte infusion within 30 days of start of therapy;

Active and uncontrolled infections.

Unresolved AEs greater than Grade from prior therapies.

History of other active malignancy (with certain exceptions)

Prior treatment with a CLK inhibitor.

Any acute or chronic graft versus host disease requiring systemic therapy within 4 weeks prior to study drug administration with the exception of topical steroids or the equivalent of 20 mg of prednisone or less.

The above is a summary, other exclusion criteria details may apply.

Applicable Disease Sites
Leukemia

Participating Institutions
UW Health Eastpark Medical Center; UW Health University Hospital