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.
≥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.
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.
Parallel
BH-30236
DrugBH-30236 will be provided as either a 5 mg, 15 mg or 30 mg tablet. Participants will take BH-30236 tablets orally depending on their dose level assignment.
Venetoclax
DrugVenetoclax will be provided as 10 mg, 50 mg or 100 mg tablets. Participants will take venetoclax orally per label instructions.
Dose Escalation: Frequency of dose limiting toxicities (DLTs)
DLTs are dose-limiting toxicities as defined in the study protocol.
Dose Escalation and Expansion: Safety evaluation of BH-30236: Number of participants with treatment-related adverse events as assessed by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0
Frequency, severity and relationship to study drug of AEs and SAEs
Dose Expansion: Composite Complete Remission (CR) Rate
Composite CR rate disease assessment in accordance with the following guidelines: European Leukemia Network (ELN) 2022 for acute myelogenous leukemia (AML) and International Working Group (IWG) 2023 for myelodysplastic syndrome (MDS).
Dose Escalation and Expansion: Maximum observed blood concentration (Cmax) of BH-30236.
Blood samples for PK analyses will be collected at predetermined time points and analyzed.
Dose Escalation: Area under the blood concentration time curve (AUC) of BH-30236.
Blood samples for PK analyses will be collected at predetermined time points and analyzed.
Dose Escalation and Expansion: Concentration before dose at steady state (Ctrough).
Blood samples for PK analyses will be collected at predetermined time points and analyzed.
Dose Escalation and Expansion: Objective Response Rate (ORR)
Objective response rate disease assessments in accordance with the following guidelines: ELN 2022 recommendations for AML and IWG 2023 for MDS (CR, CR with partial hematologic recovery \[CRh\], CR with incomplete count recovery \[CRi\], CR with limited count recovery \[CRL\], morphologic leukemia-free state \[MLFS\], or partial response \[PR\]).
Click on the lead sponsor to view all of their trials.
