A Study of BH-30236 in Relapsed/ Refractory Acute Myelogenous Leukemia and Higher Risk Myelodysplastic Syndrome

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)

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, Part 1 Dose Escalation - Monotherapy 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, Part 1 Dose Escalation - Monotherapy.

Phase 1, Part 2 Dose Escalation - Combination with Venetoclax will evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy of BH-30236 administered as a combination therapy with venetoclax. Approximately 48 participants may be enrolled in Phase 1, Part 2 Dose Escalation - Combination with Venetoclax.

Phase 1b (Dose Expansion) will follow Phase 1 to further understand the relationships among dose, exposure, toxicity, tolerability, and clinical activity. Up to 72 participants may be enrolled in Phase 1b of the study as a monotherapy or in combination with venetoclax.

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 as a monotherapy or in combination with venetoclax, in adult participants with R/R AML or HR-MDS.

The study consists of three parts: Phase 1, Part 1 Dose Escalation - Monotherapy, Phase 1, Part 2 Dose Escalation - Combination with Venetoclax, and Phase 1b Dose Expansion.

Phase 1, Part 1 Dose Escalation - Monotherapy is anticipated to enroll approximately 50 participants 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, Part 2 Dose Escalation - Combination with Venetoclax is anticipated to enroll approximately 48 participants 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 a Bayesian optimal interval (BOIN) design dose escalation, where participants will receive ascending doses of BH-30236 to determine the recommended RDEs.

Phase 1b Dose Expansion will enroll approximately 72 participants to evaluate the safety, tolerability, and preliminary anti-leukemic activity of BH-30236 as a monotherapy or in combination with venetoclax at selected RDEs determined in Phase 1 Dose Escalation.

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 ≤2.
• Adequate organ function evidenced by the following laboratory values:
• Hepatic: Transaminase levels aspartate aminotransferase [AST]/ alanine transaminase [ALT] ≤ 2.5 × upper limit of normal (ULN). In cases of liver involvement by AML or MDS, AST and ALT < 5.0 × ULN is acceptable. Total bilirubin ≤ 1.5 × ULN in the absence of documented Gilbert's disease.
• Renal: Measured or calculated creatinine clearance ≥ 60 mL/min (Cockcroft-Gault formula)

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

Exclusion Criteria:

• 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.