Study of BGB-11417 in Patients with Myeloid Malignancies

Overview

Sponsor-declared trial summary

Key facts

Sponsor

BeOne Medicines AG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

21 Mar 2022 → ongoing

Decision date (initial)

2024-03-05

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

BeiGene, Ltd.

External identifiers

EU CT number

2023-508881-14-00

EudraCT number

2021-003285-12

WHO UTN

U1111-1306-8570

ClinicalTrials.gov

NCT04771130

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Dose response, Safety, Pharmacokinetic, Pharmacodynamic

Part 1 (dose regimen finding) and Part 2 (safety expansion)
• To determine the safety and tolerability of BGB-11417 in combination with azacitidine in patients with myeloid malignancies
• To select the dose regimens of BGB-11417 in combination with azacitidine to be evaluated in Part 2 (in Part 1 only)
• To determine the recommended Phase 2 dose (RP2D) of BGB-11417 in combination with azacitidine to be evaluated in Part 3

Part 3 (efficacy expansion)
• To evaluate the antileukemic activity of BGB-11417 in combination with azacitidine as measured by response rates
• To evaluate the effect of posaconazole on the pharmacokinetics of BGB-11417 when coadministered in a drug-drug interaction (DDI) cohort
(Note: the DDI evaluation with posaconazole will not be conducted in Europe)

For monotherapy: to determine the safety and tolerability of BGB-11417 monotherapy in patients with R/R AML, MDS and MDS/MPN

Secondary objectives 1

1. Part 1 (dose regimen finding) and Part 2 (safety expansion) • To evaluate the antileukemic activity of BGB-11417 in combination with azacitidine as measured by response rates • To assess the pharmacokinetics (PK) of BGB-11417 and azacitidine when given in combination Part 3 (efficacy expansion) • To evaluate the safety and tolerability of the selected BGB-11417 dose regimen in combination with azacitidine • To evaluate the antileukemic activity of BGB-11417 in combination with azacitidine as measured by duration of responses, time to responses, and additional time-to-event outcomes • To assess the pharmacokinetics of BGB-11417 in combination with azacitidine • To evaluate the safety of BGB-11417 when coadministered with posaconazole in a DDI cohort (Note: the DDI evaluation with posaconazole will not be conducted in Europe) For monotherapy: to evaluate the antileukemic activity and assess PK of BGB-11417 monotherapy

Conditions and MedDRA coding

Myeloid malignancies (acute myeloid leukemia (AML), myelodysplastic syndromes (MDS) and myelodysplastic syndrome/myeloproliferative neoplasms (MDS/MPN.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Confirmed diagnosis of one of the following by 2016 World Health Organization criteria: • acute myeloid leukemia (AML), nonacute promyelocytic leukemia; • myelodysplastic syndrome (MDS); or • myelodysplastic syndrome/myeloproliferative neoplasms (MDS/MPN)
2. Eastern Cooperative Oncology Group (ECOG) 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.
6. Note: other protocol-defined inclusion criteria may apply.

Exclusion criteria 6

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 critera.
5. Known central nervous system involvement by leukemia.
6. Note: other protocol-defined exclusion criteria may apply.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Part 1 (dose regimen finding) and Part 2 (safety expansion) • Safety and tolerability of BGB-11417 in combination with azacitidine as assessed by dose-limiting toxicities (DLTs)and the incidence, timing, and severity of treatment-emergent adverse events (TEAEs), according to NCI-CTCAE v5.0.
2. Part 3 (efficacy expansion) • For AML: - complete remission (CR) + complete remission with partial hematologic recovery (CRh) rate; - In the DDI cohort: PK endpoints of BGB-11417, including but not limited to area under the curve (AUC) and maximum plasma concentration (Cmax), derived from the plasma concentration-time profiles
3. • For MDS: modified overall response (mOR) rate, including CR, marrow complete remission (mCR), and partial remission (PR).

Secondary endpoints 5

1. Part 1 (dose regimen finding) and Part 2 (safety expansion) For AML: • CR + morphologic complete remission with partial hematologic recovery (CRh) rate. For MDS: • Modified overall response (mOR) rate. mOR is defined as achieving a CR, marrow complete remission (mCR), or partial remission (PR) at any time point during the study per modified IWG 2006 criteria for MDS/MPN (Cheson et al 2006)
2. Secondary pharmacokinetic (PK) endpoints for both AML and MDS: • Derived PK parameters, including: − For azacitidine: maximum observed plasma concentration (Cmax), area under plasma concentration-time curve (AUC0-t, AUC0-∞), half-life (t1/2), apparent total clearance of drug from plasma (CL/F), and apparent volume of distribution (Vz/F) as appropriate; − For BGB-11417: AUClast,ss, Cmax,ss, steady-state trough plasma concentration (Ctrough,ss) and tmax,ss.
3. Part 3 (efficacy expansion) For AML: • CR rate; • CR + CR with incomplete hematologic recovery (CRi) rate; • ORR (CR + CRi + PR + morphologic leukemia-free state [MLFS]); • Duration of response of CR, CR + CRi, OR and CR + CRh; • Time to response (TTR) of CR, CR + CRi, OR and CR + CRh; • Event-free survival (EFS); • Overall survival (OS). • Transfusion independence (for at least consecutive 56-day postbaseline)
4. Part 3 (efficacy expansion) For MDS: • CR rate; • Hematological improvement – erythroid (HI-E), as per IWG 2018 criteria; • Hematological improvement – platelet (HI-P), as per IWG 2018 criteria; • Hematological improvement – neutrophil (HI-N), as per IWG 2018 criteria; • Transfusion independence (for at least consecutive 56-day post-baseline); • EFS; • OS.
5. Safety endpoints for both AML and MDS: • Safety and tolerability of BGB-11417 in combination with azacitidine or posaconazole as assessed by the incidence, timing, and severity of TEAEs, according to NCI-CTCAE v5.0.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 6

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

BeOne Medicines AG

Sponsor organisation

BeOne Medicines AG

Address

Aeschengraben 27

City

Basel

Postcode

4051

Country

Switzerland

Scientific contact point

Organisation

BeOne Medicines AG

Contact name

BeOne Medical Officer

Public contact point

Organisation

BeOne Medicines AG

Contact name

BeOne Medical Officer

Third parties 12

Locations

4 EU/EEA countries · 12 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 68 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

9 submissions — initial application plus substantial / non-substantial modifications