Clinical trial

A Phase 1b/2, Open-Label, Dose Finding, and Expansion Study of the Bcl-2 Inhibitor BGB-11417 in Patients With Myeloid Malignancies

Name

BGB-11417-103

Description

The study will determine the safety, tolerability, recommended Phase 2 dose (RP2D) and preliminary efficacy of BGB-11417 as monotherapy and in combination with azacitidine in participants with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS)or MDS/myeloproliferative neoplasm (MPN) .

Trial arms

Trial start

2021-05-24

Estimated PCD

2023-12-01

Trial end

2025-08-01

Status

Recruiting

Phase

Early phase I

Treatment

BGB-11417

Oral administration for 10, 21, 14 or 28 days on a 28-day cycle.

Arms:

Part 3: AML and MDS Cohorts, Parts 1 and 2: AML Cohorts

Other names:

Sonrotoclax

Azacitidine

Intravenous or subcutaneous administration for 7 days.

Arms:

Part 3: AML and MDS Cohorts, Parts 1 and 2: AML Cohorts, Parts 1 and 2: MDS Cohorts

Posaconazole

Oral administration for 8 days on second cycle only.

Arms:

Part 3: AML and MDS Cohorts

BGB-11417

Oral administration for 28 days on a 28-day cycle.

Arms:

Part 3: AML and MDS Cohort

BGB-11417

Oral administration for 10 or 21 days on a 28-day

Arms:

Parts 1 and 2: MDS Cohorts

Size

260

Primary endpoint

Part 1 And 2: Number Of Participants Experiencing Dose-limiting Toxicities (DLTs)

Cycle 1 (Up to 28 days for non-hematologic DLTs and up to 42 days for hematologic DLTs)

Part 1 And 2: Number Of Participants Receiving BGB-11417 In Combination With Azacitidine Experiencing Treatment-emergent Adverse Events (TEAEs)

Approximately 24 months

Part 3 AML Cohort: Complete Remission (CR) Plus CR With Partial Hematologic Recovery (CRh) Rate

Approximately 24 months

Part 3 MDS Cohort: Modified Overall Response (mOR) Rate

Approximately 24 months

Part 3 AML Cohort (DDI Sub-cohort): Area Under Plasma Concentration-time Curve (AUC) from time 0 to the last quantifiable (AUC0-t) Of BGB-11417 When Co-administered With Posaconazole

Cycle 2 Day 12 and Cycle 2 Day 20 (predose and 1, 2, 4, 6, 8, and 24 hours postdose)

Part 3 AML Cohort (DDI Sub-cohort): Maximum Observed Plasma Concentration (Cmax) Of BGB-11417 When Coadministered With Posaconazole

Cycle 2 Day 12 and Cycle 2 Day 20 (predose and 1, 2, 4, 6, 8, and 24 hours postdose)

Part 3 AML Cohort (DDI Sub-cohort): Area Under Plasma Concentration-time Curve (AUC) from time 0 to infinity (AUC0-infinity) Of BGB-11417 When Co-administered With Posaconazole

Cycle 2 Day 12 and Cycle 2 Day 20 (predose and 1, , 4, 6, 8, and 24 hours postdose)

Part 3 AML and MDS Cohorts (Treated with Monotherapy): Number Of Participants Experiencing DLTs

Cycle 2

Part 3 AML and MDS Cohorts (Treated with Monotherapy): Number of Participants Experiencing TEAEs

Approximately 24 months

Eligibility criteria

Key Inclusion Criteria: 1. Confirmed diagnosis of one of the following by 2016 World Health Organization criteria: * AML, nonacute promyelocytic leukemia * MDS * MDS/MPN 2. Eastern Cooperative Oncology Group performance status of 0 to 2. 3. Adequate organ function defined as: * Creatinine clearance ≥ 50 milliliters/minute (mL/min) (or between 30 and 49 mL/min in unfit AML cohort) * Adequate liver function 4. Life expectancy of \> 12 weeks. 5. Ability to comply with the requirements of the study. Key Exclusion Criteria: 1. A diagnosis of acute promyelocytic leukemia. 2. Prior malignancy within the past 2 years, except for curatively treated localized skin cancer, superficial bladder cancer, carcinoma in situ of the cervix or breast, or localized Gleason score ≤ 6 prostate cancer. 3. Antecedent MPN including myelofibrosis, essential thrombocytosis, polycythemia vera, or chronic myelogenous leukemia with or without BCR-ABL1 translocation and AML with BCR-ABL1 translocation. 4. Prior therapy with a B-cell lymphoma-2 inhibitor or azacitidine except for participants who meet HMA-failure criteria 5. Known central nervous system involvement by leukemia. Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Protocol

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE1', 'PHASE2'], 'designInfo': {'allocation': 'NON_RANDOMIZED', 'interventionModel': 'PARALLEL', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 260, 'type': 'ESTIMATED'}}

Updated at

2023-10-19

1 organization

3 products

3 indications

Product

BGB-11417

Organization

BeiGene

Product

Azacitidine

Indication

Acute Myeloid Leukemia

Indication

Myelodysplastic Syndromes

Indication

Myelodysplastic/Myeloproliferative Neoplasm

Product

Posaconazole