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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05006716




Registration number
NCT05006716
Ethics application status
Date submitted
9/08/2021
Date registered
16/08/2021

Titles & IDs
Public title
A Dose-Escalation and Expansion Study of BGB-16673 in Participants With B-Cell Malignancies
Scientific title
A Phase 1/2, Open-Label, Dose-Escalation and -Expansion Study of the Bruton Tyrosine Kinase Targeted Protein Degrader BGB-16673 in Patients With B-Cell Malignancies
Secondary ID [1] 0 0
2022-502157-33-00
Secondary ID [2] 0 0
BGB-16673-101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
B-cell Malignancy 0 0
Marginal Zone Lymphoma 0 0
Follicular Lymphoma 0 0
Non-Hodgkin Lymphoma 0 0
Waldenström Macroglobulinemia 0 0
Chronic Lymphocytic Leukemia 0 0
Small Lymphocytic Lymphoma 0 0
Mantle Cell Lymphoma 0 0
Diffuse Large B Cell Lymphoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - BGB-16673

Experimental: Part 1a (Monotherapy Dose Escalation) - Dose escalation in selected R/R B-Cell malignancies to inform safety, tolerability and MTD.

Experimental: Part 1b (Monotherapy Safety Expansion) - Additional participants with selected R/R B-Cell malignancies will be enrolled at selected doses to help inform the selection of the recommended phase two dose (RP2D).

Experimental: Part 1c (Additional Monotherapy Safety Expansion) - After RP2D is determined, additional safety data will be collected to confirm RP2D for participants with selected B-cell malignancies not being evaluated in Part 2

Experimental: Part 2 (Monotherapy Expansion) - The totality of the data from Part 1a, Part 1b, and Part 1c will be used to further evaluate the safety and efficacy of BGB-16673 at the recommended dose(s) for Phase 2 expansion in specific histologies.


Treatment: Drugs: BGB-16673
Orally administered

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) with adverse events leading to discontinuation, and Adverse Events (AEs) graded according NCI-CTCAE V5.
Timepoint [1] 0 0
approximately 3 years
Primary outcome [2] 0 0
Recommended Phase 2 Dose (RP2D) of BGB-16673
Timepoint [2] 0 0
approximately 3 years
Primary outcome [3] 0 0
Maximum Tolerated Dose (MTD) of BGB-16673
Timepoint [3] 0 0
approximately 3 years
Primary outcome [4] 0 0
Phase 2: Overall response rate (ORR)
Timepoint [4] 0 0
approximately 3 years
Secondary outcome [1] 0 0
Single Dose Maximum observed plasma concentration (Cmax) of BGB-16673
Timepoint [1] 0 0
Day 1 pre-dose and 2, 4, 6,8,24, 48 and 72 hours post-dose (approximately 2 years)
Secondary outcome [2] 0 0
Single Dose Minimum observed plasma concentration (Cmin) of BGB-16673
Timepoint [2] 0 0
Day 1 pre-dose and 2, 4, 6,8,24, 48 and 72 hours post-dose (approximately 2 years)
Secondary outcome [3] 0 0
Single Dose Time to reach Cmax (tmax) of BGB-16673
Timepoint [3] 0 0
Day 1 pre-dose and 2, 4, 6,8,24, 48 and 72 hours post-dose (approximately 2 years)
Secondary outcome [4] 0 0
Single Dose Time to reach half of Cmax (T1/2) of BGB-16673
Timepoint [4] 0 0
Day 1 pre-dose and 2, 4, 6,8,24, 48 and 72 hours post-dose (approximately 2 years)
Secondary outcome [5] 0 0
Single Dose Area under the plasma concentration-time curve (AUC) of BGB-16673
Timepoint [5] 0 0
Day 1 pre-dose and 2, 4, 6,8,24, 48 and 72 hours post-dose (approximately 2 years)
Secondary outcome [6] 0 0
Single Dose apparent total clearance of drug from plasma after oral administration (CL/F) of BGB-16673
Timepoint [6] 0 0
Day 1 pre-dose and 2, 4, 6,8,24, 48 and 72 hours post-dose (approximately 2 years)
Secondary outcome [7] 0 0
Single Dose apparent volume of distribution (Vz/F) of BGB-16673
Timepoint [7] 0 0
Day 1 pre-dose and 2, 4, 6,8,24, 48 and 72 hours post-dose (approximately 2 years)
Secondary outcome [8] 0 0
Single Dose accumulation ratios of BGB-16673
Timepoint [8] 0 0
Day 1 pre-dose and 2, 4, 6,8,24, 48 and 72 hours post-dose (approximately 2 years)
Secondary outcome [9] 0 0
Steady State Maximum observed plasma concentration (Cmax) of BGB-16673
Timepoint [9] 0 0
Day 1 pre-dose and 2, 4, 6,8,24, 48 and 72 hours post-dose (approximately 2 years)
Secondary outcome [10] 0 0
Steady State minimum observed plasma concentration (Cmin) of BGB-16673
Timepoint [10] 0 0
Day 1 pre-dose and 2, 4, 6,8,24, 48 and 72 hours post-dose (approximately 2 years)
Secondary outcome [11] 0 0
Steady State Time to reach Cmax (tmax) of BGB-16673
Timepoint [11] 0 0
Day 1 pre-dose and 2, 4, 6,8,24, 48 and 72 hours post-dose (approximately 2 years)
Secondary outcome [12] 0 0
Steady State Time to reach half of Cmax (T1/2) of BGB-16673
Timepoint [12] 0 0
Day 1 pre-dose and 2, 4, 6,8,24, 48 and 72 hours post-dose (approximately 2 years)
Secondary outcome [13] 0 0
Steady State Area under the plasma concentration-time curve (AUC) of BGB-16673
Timepoint [13] 0 0
Day 1 pre-dose and 2, 4, 6,8,24, 48 and 72 hours post-dose (approximately 2 years)
Secondary outcome [14] 0 0
Steady State apparent total clearance of drug from plasma after oral administration (CL/F) of BGB-16673
Timepoint [14] 0 0
Day 1 pre-dose and 2, 4, 6,8,24, 48 and 72 hours post-dose (approximately 2 years)
Secondary outcome [15] 0 0
Steady State apparent volume of distribution (Vz/F) of BGB-16673
Timepoint [15] 0 0
Day 1 pre-dose and 2, 4, 6,8,24, 48 and 72 hours post-dose (approximately 2 years)
Secondary outcome [16] 0 0
Bruton's tyrosine kinase (BTK) protein degradation in peripheral blood after BGB-16673 monotherapy
Timepoint [16] 0 0
Day 1 pre-dose and 8 hours post-dose (approximately 2 years)
Secondary outcome [17] 0 0
Phase 1: Overall response rate (ORR)
Timepoint [17] 0 0
approximately 3 years
Secondary outcome [18] 0 0
Phase 1: Number of Waldenström Macroglobulinemia (WM) Participants with major response rate (MRR)
Timepoint [18] 0 0
approximately 3 years
Secondary outcome [19] 0 0
Phase 2: Duration of Response (DOR)
Timepoint [19] 0 0
approximately 3 years
Secondary outcome [20] 0 0
Phase 2: Time to Response (TTR)
Timepoint [20] 0 0
approximately 3 years
Secondary outcome [21] 0 0
Phase 2: Progression- Free Survival (PFS)
Timepoint [21] 0 0
approximately 3 years
Secondary outcome [22] 0 0
Phase 2: Overall Survival (OS)
Timepoint [22] 0 0
approximately 3 years
Secondary outcome [23] 0 0
Phase 2 (Cohort 1): Best Overall Response (BOR) of partial response with lymphocytosis or better
Timepoint [23] 0 0
approximately 3 years
Secondary outcome [24] 0 0
Phase 2 (Cohort 3): BOR of minor response or better
Timepoint [24] 0 0
approximately 3 years
Secondary outcome [25] 0 0
Phase 2 (Cohort 1): Participant-reported outcomes (PRO) via Functional Assessment of Cancer Therapy-Leukemia (FACT-Leu) questionarre
Timepoint [25] 0 0
approximately 3 years
Secondary outcome [26] 0 0
Phase 2 (Cohort 2): Participant-reported outcomes (PRO) via National Comprehensive Cancer Network/Functional Assessment of Cancer Therapy Lymphoma Cancer Symptom Index - 18 (NFLymSI-18)
Timepoint [26] 0 0
approximately 3 years

Eligibility
Key inclusion criteria
Inclusion Criteria :

1. Confirmed diagnosis (per World Health Organization (WHO) guidelines, unless otherwise noted) of one of the following: Marginal Zone Lymphoma (MZL) , Follicular Lymphoma (FL), R/R Mantle Cell Lymphoma (MCL), R/R chronic lymphocytic leukemia and small lymphocytic lymphoma (CLL/SLL), Waldenström macroglobulinemia (WM), Diffuse large B-cell lymphoma (DLBCL), or >2 treatments per the Richter's transformation to DLBCL.
2. Participants who have previously received a covalently-binding Bruton´s tyrosine kinase (BTK) inhibitor (BTKi) in any line of therapy must have received treatment with the BTK inhibitor for = 8 weeks (unless reason for discontinuation is intolerance).
3. For dose-finding and dose-expansion, participants who had previously received a covalently-binding BTK inhibitor as monotherapy or in combination with other anticancer agents are eligible for the study if they meet any of the following criteria: discontinued the previous BTK inhibitor due to disease progression, experienced disease progression after completing treatment with a BTK inhibitor or discontinued the BTK inhibitor due to toxicity or intolerance.
4. Measurable disease by radiographic assessment or serum IgM level (WM only)
5. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2
6. Participants enrolling in the dose finding phase of the study may be previously treated with a BTKi or may be naïve to BTKi therapy depending on the diagnosis and country of enrollment; participants with MCL enrolling in the expansion cohorts (Phase 2) must have been treated with a BTKi in a prior line of therapy; CLL/SLL participants, in addition to being treated with a BTKi in a prior line of therapy, must also have received a Bcl-2 inhibitor in a prior line of therapy as well (Phase 2).
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Prior malignancy (other than the disease under study) within the past 2 years, except in situ malignancies that have been curatively resected, localized breast cancer treated with curative intent with no evidence of breast active disease for more than 3 years and receiving adjuvant hormonal therapy, localized Gleason score = 6 prostate cancer undergoing observation or treatment with androgen depravation, or any other cancer treated with curative intent, not on adjuvant treatment, and in the opinion of the investigator is unlikely to recur.
2. Requires ongoing systemic treatment for any other malignancy
3. Requires ongoing systemic (defined as = 10 mg/day of prednisone or equivalent) corticosteroid treatment.
4. Current or history of central nervous system involvement including the brain, spinal cord, leptomeninges, and cerebrospinal fluid (as documented by imaging, cytology, or biopsy) by B-cell malignancy, regardless of whether participants had received treatment for central nervous system disease
5. Known active plasma cell neoplasm, prolymphocytic leukemia, T-cell lymphoma, Burkitt lymphoma, acquired immunodeficiency syndrome (AIDS)-related B-cell lymphoma, Castleman disease, post-transplant lymphoproliferative disorders, hairy cell leukemia, germinal center B-cell (GCB), DLBCL, EBV+ DLBCL NOS, primary DLBCL of the central nervous system (CNS), primary cutaneous DLBCL - leg type, DLBCL associated with chronic inflammation, primary mediastinal (thymic) large B-cell lymphoma, intravascular large B-cell lymphoma, ALK+ large B-cell lymphoma, primary effusion lymphoma, high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements, high-grade B-cell lymphoma - NOS, B-cell lymphoma unclassifiable with features intermediate between DLBCL and classical Hodgkin lymphoma, or history of or currently suspected transformation of an indolent lymphoma to an aggressive histology (except for participants with Richter Transformation to DLBCL are eligible for Part 1a, 1c, or Phase 2 and participants with history of follicular lymphoma transforming to non-GCB DLBCL who are eligible for Part 1a, 1c, or Phase 2).

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC,WA
Recruitment hospital [1] 0 0
Concord Repatriation General Hospital - Concord
Recruitment hospital [2] 0 0
Princess Alexandra Hospital - Brisbane
Recruitment hospital [3] 0 0
St Vincents Hospital Melbourne - Fitzroy
Recruitment hospital [4] 0 0
Peninsula Private Hospital - Frankston
Recruitment hospital [5] 0 0
Peter Maccallum Cancer Centre - Melbourne
Recruitment hospital [6] 0 0
The Alfred Hospital - Melbourne
Recruitment hospital [7] 0 0
Linear Clinical Research - Nedlands
Recruitment hospital [8] 0 0
Perth Blood Institute - West Perth
Recruitment postcode(s) [1] 0 0
2139 - Concord
Recruitment postcode(s) [2] 0 0
4102 - Brisbane
Recruitment postcode(s) [3] 0 0
3065 - Fitzroy
Recruitment postcode(s) [4] 0 0
3199 - Frankston
Recruitment postcode(s) [5] 0 0
3000 - Melbourne
Recruitment postcode(s) [6] 0 0
3004 - Melbourne
Recruitment postcode(s) [7] 0 0
6009 - Nedlands
Recruitment postcode(s) [8] 0 0
6005 - West Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Colorado
Country [5] 0 0
United States of America
State/province [5] 0 0
Florida
Country [6] 0 0
United States of America
State/province [6] 0 0
Georgia
Country [7] 0 0
United States of America
State/province [7] 0 0
Illinois
Country [8] 0 0
United States of America
State/province [8] 0 0
Iowa
Country [9] 0 0
United States of America
State/province [9] 0 0
Kentucky
Country [10] 0 0
United States of America
State/province [10] 0 0
Louisiana
Country [11] 0 0
United States of America
State/province [11] 0 0
Maryland
Country [12] 0 0
United States of America
State/province [12] 0 0
Massachusetts
Country [13] 0 0
United States of America
State/province [13] 0 0
Michigan
Country [14] 0 0
United States of America
State/province [14] 0 0
Minnesota
Country [15] 0 0
United States of America
State/province [15] 0 0
Nebraska
Country [16] 0 0
United States of America
State/province [16] 0 0
Nevada
Country [17] 0 0
United States of America
State/province [17] 0 0
New Jersey
Country [18] 0 0
United States of America
State/province [18] 0 0
New York
Country [19] 0 0
United States of America
State/province [19] 0 0
Texas
Country [20] 0 0
United States of America
State/province [20] 0 0
Virginia
Country [21] 0 0
United States of America
State/province [21] 0 0
Washington
Country [22] 0 0
Brazil
State/province [22] 0 0
Caxias do Sul
Country [23] 0 0
Brazil
State/province [23] 0 0
Curitiba
Country [24] 0 0
Brazil
State/province [24] 0 0
Porto Alegre
Country [25] 0 0
Brazil
State/province [25] 0 0
Sao Paulo
Country [26] 0 0
Brazil
State/province [26] 0 0
Vitoria
Country [27] 0 0
Canada
State/province [27] 0 0
Alberta
Country [28] 0 0
Canada
State/province [28] 0 0
Ontario
Country [29] 0 0
Canada
State/province [29] 0 0
Quebec
Country [30] 0 0
France
State/province [30] 0 0
Bordeaux
Country [31] 0 0
France
State/province [31] 0 0
Clermont Ferrand
Country [32] 0 0
France
State/province [32] 0 0
Creteil
Country [33] 0 0
France
State/province [33] 0 0
Lille
Country [34] 0 0
France
State/province [34] 0 0
Lyon Cedex
Country [35] 0 0
France
State/province [35] 0 0
Marseille
Country [36] 0 0
France
State/province [36] 0 0
Montpellier Cedex
Country [37] 0 0
France
State/province [37] 0 0
Paris
Country [38] 0 0
France
State/province [38] 0 0
Rouen Cedex
Country [39] 0 0
Georgia
State/province [39] 0 0
Tbilisi
Country [40] 0 0
Germany
State/province [40] 0 0
Dresden
Country [41] 0 0
Germany
State/province [41] 0 0
Luebeck
Country [42] 0 0
Germany
State/province [42] 0 0
Mainz
Country [43] 0 0
Germany
State/province [43] 0 0
Munich
Country [44] 0 0
Germany
State/province [44] 0 0
Ulm
Country [45] 0 0
Italy
State/province [45] 0 0
Bologna
Country [46] 0 0
Italy
State/province [46] 0 0
Milano
Country [47] 0 0
Italy
State/province [47] 0 0
Roma
Country [48] 0 0
Italy
State/province [48] 0 0
Verona
Country [49] 0 0
Korea, Republic of
State/province [49] 0 0
Busan Gwang'yeogsi
Country [50] 0 0
Korea, Republic of
State/province [50] 0 0
Seoul Teugbyeolsi
Country [51] 0 0
Moldova, Republic of
State/province [51] 0 0
Chisinau
Country [52] 0 0
Spain
State/province [52] 0 0
Barcelona
Country [53] 0 0
Spain
State/province [53] 0 0
Madrid
Country [54] 0 0
Spain
State/province [54] 0 0
Majadahonda
Country [55] 0 0
Spain
State/province [55] 0 0
Valencia
Country [56] 0 0
Sweden
State/province [56] 0 0
Goteborg
Country [57] 0 0
Sweden
State/province [57] 0 0
Stockholm
Country [58] 0 0
Sweden
State/province [58] 0 0
Uppsala
Country [59] 0 0
Turkey
State/province [59] 0 0
Ankara
Country [60] 0 0
Turkey
State/province [60] 0 0
Kayseri
Country [61] 0 0
Turkey
State/province [61] 0 0
Samsun
Country [62] 0 0
United Kingdom
State/province [62] 0 0
Headington
Country [63] 0 0
United Kingdom
State/province [63] 0 0
Leeds
Country [64] 0 0
United Kingdom
State/province [64] 0 0
NewCastle Upon Tyne
Country [65] 0 0
United Kingdom
State/province [65] 0 0
Plymouth

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
BeiGene
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
BeiGene
Address 0 0
Country 0 0
Phone 0 0
1.877.828.5568
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.