A Study of BGB-11417 in Participants With Myeloid Malignancies

Phase 2RecruitingNCT04771130

BeiGene260 enrolled

Overview

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) .

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

260

Conditions

Acute Myeloid Leukemia Myelodysplastic Syndromes Myelodysplastic/Myeloproliferative Neoplasm

Interventions

BGB-11417DRUG

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

AzacitidineDRUG

Intravenous or subcutaneous administration for 7 days.

PosaconazoleDRUG

Oral administration for 8 days on second cycle only.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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. History of prior malignancy, with the exception of either a history of MDS or MDS/MPN that has transformed to AML, or other prior malignancy that was treated with a full curative intent and no evidence of recurrence within the past 2 years (eg, 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 5. Known central nervous system involvement by leukemia. Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Locations (46)

Outcomes

Primary Outcomes

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

Time frame: 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 Experiencing Treatment-emergent Adverse Events (TEAEs)

Time frame: Approximately 24 months

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

CR plus CRh will be defined as the percentage of participants whose best overall response (BOR) is CR plus CRh. BOR will be defined as the best response recorded from the first dose of study drug until data cut or the initiation of new anticancer treatment.

Time frame: Approximately 24 months

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

The mOR will be defined as the percentage of participants whose BOR is achieving CR, marrow complete remission (mCR), or partial remission (PR) at any time point during the study for myelodysplastic/myeloproliferative neoplasm (MDS/MPN).

Time frame: Approximately 24 months

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

Time frame: 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 Administered Alone and When Co-administered With Posaconazole

Time frame: 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 Administered Alone and When Co-administered With Posaconazole

Central Contacts

BeiGene

CONTACT

1.877.828.5568 clinicaltrials@beigene.com

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

City of Hope National Medical Center

Duarte, California, United States

TERMINATED

Tampa General Hospital

Tampa, Florida, United States

RECRUITING

Upmc Hillman Cancer Center(Univ of Pittsburgh)

Pittsburgh, Pennsylvania, United States

RECRUITING

Md Anderson Cancer Center

Houston, Texas, United States

RECRUITING

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

RECRUITING

Concord Repatriation General Hospital

Concord, New South Wales, Australia

RECRUITING

St George Hospital

Kogarah, New South Wales, Australia

RECRUITING

Orange Health Hospital

Orange, New South Wales, Australia

RECRUITING

Gold Coast University Hospital

Southport, Queensland, Australia

RECRUITING

Monash Health

Clayton, Victoria, Australia

RECRUITING

...and 36 more locations

Secondary Outcomes

Parts 1 And 2 AML Cohort: Complete remission (CR) + Morphologic CR With Partial Hematologic Recovery (CRh)

Time frame: Approximately 24 months

Parts 1 And 2 MDS Cohort: mOR Rate

Time frame: Approximately 24 months

Parts 1 And 2: Cmax Of Azacitidine When Coadministered With BGB-11417

Time frame: Day 0 and 4 (Cycle 1) predose and at multiple time points up to 4 hours postdose

Parts 1 And 2: Terminal Half-life (t1/2) Of Azacitidine When Coadministered With BGB-11417

Time frame: Day 0 and 4 (Cycle 1) predose and at multiple time points up to 4 hours postdose

Parts 1 And 2: AUC From Time Zero To Time t (AUC0-t) Of Azacitidine When Coadministered With BGB-11417

Time frame: Day 0 and 4 (Cycle 1) predose and at multiple time points up to 4 hours postdose

Parts 1 And 2: AUC From Time Zero To Infinity (AUC0-inf) Of Azacitidine When Coadministered With BGB-11417

Time frame: Day 0 and 4 (Cycle 1) predose and at multiple time points up to 4 hours postdose

Parts 1 And 2: Apparent Total Clearance Of Azacitidine From Plasma (CL/F) When Coadministered With BGB-11417

Time frame: Day 0 and 4 (Cycle 1) predose and at multiple time points up to 4 hours postdose

Parts 1 And 2: Apparent Volume Of Distribution (Vz/F) Of Azacitidine When Coadministered With BGB-11417

Time frame: Day 0 and 4 (Cycle 1) predose and at multiple time points up to 4 hours postdose

Parts 1 And 2: Steady-state AUC From Time Zero To Time Of Last Measurable Concentration (AUClast,ss) Of BGB-11417 When Coadministered With Azacitidine

Time frame: Day 1-4 and 28 (Cycle 1) Day 5 (Cycle 2) predose and at multiple time points up to 8 hours postdose

Parts 1 And 2: Steady-state Cmax (Cmax,ss) Of BGB-11417 When Coadministered With Azacitidine

Time frame: Day 1-4 and 28 (Cycle 1) Day 5 (Cycle 2) predose and at multiple time points up to 8 hours postdose

Parts 1 And 2: Steady-state Trough Plasma Concentration (Ctrough,ss) Of BGB-11417 When Coadministered With Azacitidine

Time frame: Day 1-4 and 28 (Cycle 1) Day 5 (Cycle 2) predose and at multiple time points up to 8 hours postdose

Parts 1 And 2: Steady-state Time To Maximum Observed Plasma Concentration (tmax,ss) Of BGB-11417 When Coadministered With Azacitidine

Time frame: Day 1-4 and 28 (Cycle 1) Day 5 (Cycle 2) predose and at multiple time points up to 8 hours postdose

Part 3: Number Of Participants Experiencing TEAEs

Time frame: Approximately 24 months

Part 3: Complete Response Rate

CR will be defined as the percentage of participants whose BOR is CR. BOR will be defined as the best response recorded from the first dose of study drug until data cut or the initiation of new anticancer treatment.

Time frame: Approximately 24 months

Part 3 AML Cohort: CR With Incomplete Hematologic Recovery (CRi) Rate

CRi will be defined as the percentage of participants whose BOR is CRi.

Time frame: Approximately 24 months

Part 3 AML Cohort: Overall Response Rate (ORR)

The ORR will include participants whose BOR include CR, CRi, PR, and morphologic leukemia-free state.

Time frame: Approximately 24 months

Part 3 AML Cohort: Duration Of Response (DOR)

DOR will be defined as the time from the first response to disease progression documented after treatment initiation or death, whichever occurs first. DOR will include CR, CR plus CRi, overall response (OR), and CR plus CRh.

Time frame: Approximately 24 months

Part 3 AML Cohort: Time To Response (TTR)

TTR will be defined as the time from treatment initiation to the first documented response and will include CR, CR plus CRi, OR, and CR plus CRh.

Time frame: Approximately 24 months

Part 3 Event-free Survival (EFS)

EFS will be defined as the time from treatment initiation to disease progression, treatment failure, relapse (hematologic relapse for AML) for those who have treatment success, or death due to any cause, whichever happens first.

Time frame: Approximately 24 months

Part 3 Overall Survival (OS)

OS will be defined as the time from treatment initiation to death. OS will be analyzed using the same methods as the EFS analysis except for the censoring rules.

Time frame: Approximately 24 months

Part 3 AML Cohort: Number of Participants with Transfusion Independence

Transfusion independence will be defined as the proportion of participants whose BOR is transfusion independence. Transfusion independence will need to last for at least 56 consecutive days postbaseline.

Time frame: Approximately 24 months

Part 3 MDS Cohort: Number Of Participants With Hematological Improvement-erythroid (HI-E)

The proportion of participants whose BOR is HI-E

Time frame: Approximately 24 months

Part 3 MDS Cohort: Proportion Of Participants With Hematological Improvement-platelet (HI-P)

The proportion of participants whose BOR is HI-P

Time frame: Approximately 24 months

Part 3 MDS Cohort: Proportion Of Participants With Hematological Improvement-neutrophil (HI-N)

The proportion of participants whose BOR is HI-N will be reported.

Time frame: Approximately 24 months

Part 3 MDS Cohort: Number of participants with Transfusion Independence

Transfusion independence will be defined as the percentage of participants whose BOR is transfusion independence. Transfusion independence will need to last for at least 56 consecutive days postbaseline.

Time frame: Approximately 24 months

Part 3: Ctrough,ss Of BGB-11417 When Coadministered With Azacitidine

Time frame: Cycle 1 Day 1 and Cycle 2 Day 5 (predose and 4 and 6 hours postdose)

Part 3 MDS cohort: Partial Hematologic Recovery CRh

Percentage of participants with partial hematologic recovery will be reported

Time frame: Approximately 24 months

Part 3 AML (Treated with Monotherapy): Complete Response + Morphologic complete Remission with Partial Hematologic Recovery

Percentage of participants with Complete Response + Morphologic complete Remission with Partial Hematologic Recovery will be reported.

Time frame: Approximately 24 months

Part 3 AML (Treated with Monotherapy): Steady State trough plasma concentration of BGB-11417

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

Part 3 MDS (Treated with Monotherapy): Modified Overall Response

Percentage of participants with modified overall response including CR, marrow CR (mCR) or partial remission (PR)

Time frame: Approximately 24 months

Part 3 MDS (Treated with Monotherapy): Steady State trough plasma concentration of BGB-11417

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