Myeloid Malignancy
Conditions
Keywords
KAT6 inhibitor
Brief summary
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and preliminary efficacy of BG-75202 (KAT6A/B inhibitor) alone and in combination with other agents in patients with myeloid malignancies.
Interventions
DRUGBG-75202
Administered orally
DRUGHypomethylation Agent (HMA)
Administered Intravenous (IV) or Subcutaneous (SC)
Sponsors
BeOne Medicines
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients must be ≥ 18 years of age (or the legal age of consent in the jurisdiction in which the study is taking place), inclusive, at the time of signing the Informed consent form (ICF). * Patients must have a confirmed diagnosis of myeloid malignancies based on 2016 World Health Organization criteria, and meet the following categories: * Relapsed/refractory; myeloid malignancies after ≥1 prior systemic therapy, per ELN; 2022 criteria; patients with actionable genetic alteration must have previously received targeted therapies unless contraindicated, unavailable/inaccessible, or declined by patient. * Patients must have a stable Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2.
Exclusion criteria
* Prior exposure to KAT6A/B inhibitors/degraders. * A diagnosis of acute promyelocytic leukemia or BCR-ABL-positive leukemia. * Known central nervous system involvement by leukemia * Use of antileukemic therapies without sufficient washout period Note: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1a: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) | From first dose to 30 days after last dose or initiation of a new anticancer therapy, whichever occurs first, up to approximately18 months | An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporarily associated with the use of study treatment, whether considered related to study treatment or not. An SAE is any untoward medical occurrence that, at any dose, * Results in death * Is life-threatening * Requires hospitalization or prolongation of existing hospitalization * Results in disability/incapacity * Is congenital anomaly/birth defect * Is considered a significant medical AE by the investigator based on medical judgement |
| Phase 1a: Recommended Dose for Expansion (RDFE) of BG-75202 | Estimated approximately 18 months | The potential RDFE(s) of BG-75202 as monotherapy or in combination with HMA are based upon the maximum tolerated dose (MTD) or maximum administered dose (MAD), with consideration of the tolerability, pharmacokinetics (PK), pharmacodynamics, antitumor activity, and any other available relevant data. |
| Phase 1b: Dose Optimization: Complete Remission (CR) Rate | Up to approximately 12 months | CR rate is defined as the percentage of participants who achieved a best response of CR as assessed by investigator's review. |
| Phase 1b: Dose Optimization: Complete Remission (CR) plus CR With Partial Hematologic Recovery (CRh) Rate | Up to approximately 12 months | CR + CRh rate is defined as the percentage of participants who achieved the best response of CR or CRh as assessed by investigator's review. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1b Dose Optimization: Number of Participants with Adverse Events (AEs) | From first dose to 30 days after last dose or initiation of a new anticancer therapy, whichever occurs first, up to approximately 18 months | An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporarily associated with the use of study treatment, whether considered related to study treatment or not. |
| Phase 1b: Time to Response (TTR) | Up to approximately 12 months | TTR for CR, CR + CRi, CR + CRh, and ORR, defined as the time from the randomization date, to the first determination of the respective objective response. |
| Phase 1b: CR + Complete Remission with Incomplete Hematologic Recovery (CRi) Rate | Up to approximately 12 months | CR + CRi rate is defined as the percentage of patients who achieved a best response of CR or CRi as assessed by investigator's review. |
| Phase 1a: Dose Escalation: CR + CRh Rate | Up to approximately 12 months | CR + CRh rate is defined as the percentage of patients who achieved a best response of CR or CRh as assessed by investigator's review. |
| Phase 1a and Phase 1b: Overall response rate (ORR) | Up to approximately 12 months | ORR is defined as the percentage of participants who achieved a best response of CR, CRh, CRi, or partial response (PR) as assessed by investigator's review. |
| Phase 1b: Event Free Survival (EFS) | Up to approximately 18 months | EFS, defined as the time from the randomization date for Phase 1b, to the date of first documentation of treatment failure per European LeukemiaNet (ELN) 2022 (refractory disease and relapsed disease) or death due to any cause, whichever occurs first. |
| Phase 1b: Overall Survival (OS) | Up to approximately 18 months | OS, defined as the time from the randomization date for Phase to the date of death due to any cause. |
| Phase 1b: Transfusion Independence | Up to approximately 12 months | Transfusion independence, defined as the proportion of patients who achieve red blood cell and/or platelet transfusion independence according to protocol specified criteria, among patients who are transfusion-dependent at baseline. |
| Phase 1a and Phase 1b: Observed Plasma Maximum Concentration (Cmax) of BG-75202 | Up to approximately 5 months | — |
| Phase 1a and Phase 1b: Minimum Observed Plasma Concentration (Ctrough) of BG-75202 | Up to approximately 5 months | — |
| Phase 1a and Phase 1b: Area Under the Plasma Concentration-Time Curve (AUC) of BG-75202 | Up to approximately 5 months | — |
| Phase 1a and Phase 1b: Terminal Half Life (t1/2) of BG-75202 | Up to approximately 5 months | — |
| Phase 1b: Recommended Phase 2 Dose (RP2D) | Up to approximately 18 months | The RP2D of BG-75202 takes into consideration the totality of data including, but not limited to, PK, pharmacodynamics, safety, tolerability, and antitumor activity. |
Countries
Australia, China, New Zealand
Contacts
CONTACTStudy Director
STUDY_DIRECTORStudy Director
BeOne Medicine
Outcome results
None listed