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

BlossomHill Therapeutics

Status and phase

Enrolling

Phase 1

Conditions

Refractory Acute Myeloid Leukemia

Leukemia, Myeloid, Acute

Leukemia

Myelodysplastic Syndromes

Leukemia, Myeloid

Preleukemia

Treatments

Drug: BH-30236

Drug: Venetoclax

Study type

Interventional

Funder types

Industry

Identifiers

NCT06501196

BH-30236-01

Details and patient eligibility

About

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.

Full description

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.

Enrollment

170 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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.

Trial design

Primary purpose

Treatment

Allocation

Non-Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

170 participants in 4 patient groups

Dose Escalation Cohort - Monotherapy

Experimental group

Description:

BH-30236 Monotherapy for Dose Escalation

Treatment:

Drug: BH-30236

Dose Escalation Cohort - Combination with Venetoclax

Experimental group

Description:

BH-30236 in Combination with Venetoclax for Dose Escalation.

Treatment:

Drug: Venetoclax

Drug: BH-30236

Dose Expansion Cohort - Monotherapy

Experimental group

Description:

BH-30236 based on Monotherapy dose escalation data.

Treatment:

Drug: BH-30236

Dose Expansion Cohort - Combination with Venetoclax

Experimental group

Description:

BH-30236 in Combination with Venetoclax based on Dose Escalation data

Treatment:

Drug: Venetoclax

Drug: BH-30236

Trial contacts and locations

Central trial contact

Sponsor Contact

Data sourced from clinicaltrials.gov

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