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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04277637




Registration number
NCT04277637
Ethics application status
Date submitted
18/02/2020
Date registered
20/02/2020
Date last updated
25/03/2025

Titles & IDs
Public title
Study of Bcl-2 Inhibitor Sonrotoclax (BGB-11417) in Participants With Mature B-Cell Malignancies
Scientific title
A Phase 1a/1b Open-Label Dose Escalation and Expansion Study of Bcl-2 Inhibitor BGB-11417 in Patients With Mature B-Cell Malignancies
Secondary ID [1] 0 0
2024-515592-35-00
Secondary ID [2] 0 0
BGB-11417-101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Mature B-Cell Malignancies 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Sonrotoclax
Treatment: Drugs - Zanubrutinib
Treatment: Drugs - Obinutuzumab

Experimental: Sonrotoclax Monotherapy Dose Finding: Part 1 - Participants with relapsed/refractory (R/R) non-Hodgkin lymphoma (NHL) including follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), marginal zone lymphoma (MZL) or transformed NHL, mantle cell lymphoma (MCL); Waldenströms macroglobulinemia (WM); and chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) will receive oral sonrotoclax evaluated as monotherapy.

Experimental: Sonrotoclax Monotherapy Expansion Cohorts: Part 2 - Participants with R/R indolent NHL including FL, MZL; aggressive NHL including DLBCL, transformed NHL; CLL/SLL with low tumor burden or low creatine clearance; CLL/SLL with without high tumor burden or low creatine clearance will receive oral sonrotoclax at the RP2D dose to further define the safety profile.

Experimental: Sonrotoclax + Zanubrutinib Combination Therapy Dose Finding: Part 3 - Participants with R/R MCL, R/R or treatment-naïve (TN) CLL/SLL will receive oral sonrotoclax in combination with zanubrutinib.

Experimental: Sonrotoclax + Zanubrutinib Combination Therapy Dose Expansion: Part 4 - Participants with R/R indolent NHL including FL, MZL; aggressive NHL including DLBCL, transformed NHL; R/R MCL; R/R or treatment-naïve (TN) CLL/SLL will receive oral sonrotoclax in combination with zanubrutinib at an RP2D dose to further define the safety profile.

Experimental: Sonrotoclax + Zanubrutinib Combination Therapy Dose Escalation: Part 5 - Participants with treatment naïve CLL/SLL will receive oral sonrotoclax in combination with obinutuzumab without and with zanubrutinib.

Experimental: Sonrotoclax + Zanubrutinib Combination Therapy Dose Expansion: Part 6 - Participants with treatment naïve CLL/SLL will receive oral sonrotoclax in combination with obinutuzumab without and with zanubrutinib at an RP2D dose to further define the safety profile.


Treatment: Drugs: Sonrotoclax
Film-coated tablets administered once daily at a dose as specified in the treatment arm

Treatment: Drugs: Zanubrutinib
320 mg daily administered as two 80-mg capsules twice a day (160 mg twice a day) or as four 80-mg capsules once a day (320 mg once a day)

Treatment: Drugs: Obinutuzumab
Given as an intravenous infusion administered per label.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants Experiencing Treatment Emergent Adverse Events (TEAEs)
Timepoint [1] 0 0
Up to 30 days after the last dose of study drug, an average of 18 months
Primary outcome [2] 0 0
Number of Participants Experiencing Serious Adverse Events (SAEs)
Timepoint [2] 0 0
Up to 30 days after the last dose of study drug, an average of 18 months
Primary outcome [3] 0 0
Number of Participants Experiencing Adverse Events (AEs) leading to discontinuation of Sonrotoclax
Timepoint [3] 0 0
Up to 30 days after the last dose of study drug, an average of 18 months
Primary outcome [4] 0 0
Part 1, Part 3: Maximum Tolerated Dose (MTD) of Sonrotoclax
Timepoint [4] 0 0
Up to approximately 2 months
Primary outcome [5] 0 0
Part 1, Part 3, Part 5: RP2D of Sonrotoclax
Timepoint [5] 0 0
Day 1 to last dose of study drug, an average of 18 months
Primary outcome [6] 0 0
Part 1, Part 3, Part 5: Number of participants experiencing tumor lysis syndrome (TLS) relevant events
Timepoint [6] 0 0
Up to 30 days after the last dose of study drug, an average of 18 months
Primary outcome [7] 0 0
Part 1, Part 3, Part 5: Number of Participants Experiencing Dose-Limiting Toxicities (DLTs
Timepoint [7] 0 0
Up to approximately 2 months
Secondary outcome [1] 0 0
Maximum Observed Plasma Concentration (Cmax) After a Single Dose of Sonrotoclax
Timepoint [1] 0 0
Predose up to 12 hours postdose
Secondary outcome [2] 0 0
Area Under the Concentration-Time Curve from Time 0 to the Last Quantifiable Concentration (AUC0-last) After a Single Dose of Sonrotoclax
Timepoint [2] 0 0
Predose up to 12 hours postdose
Secondary outcome [3] 0 0
Area Under the Concentration-Time Curve from Time 0 to Infinity (AUC0-8) After a Single Dose of Sonrotoclax
Timepoint [3] 0 0
Predose up to 12 hours postdose
Secondary outcome [4] 0 0
Time Taken for Half the Initial Dose Administered to Be Eliminated from The Body (T1/2) of Sonrotoclax
Timepoint [4] 0 0
Predose up to 12 hours postdose
Secondary outcome [5] 0 0
Time to Maximum Plasma Concentration (Tmax) After a Single Dose of Sonrotoclax
Timepoint [5] 0 0
Predose up to 12 hours postdose
Secondary outcome [6] 0 0
Apparent Clearance (CL/F) After a Single Dose of Sonrotoclax
Timepoint [6] 0 0
Predose up to 12 hours postdose
Secondary outcome [7] 0 0
Apparent volume of distribution (Vz/F) After a Single Dose of Sonrotoclax
Timepoint [7] 0 0
Predose up to 12 hours postdose
Secondary outcome [8] 0 0
Steady State Area Under the Concentration-Time Curve of 0 - Last Day (AUCLast, ss) of Sonrotoclax
Timepoint [8] 0 0
Predose up to 12 hours postdose
Secondary outcome [9] 0 0
Part 3, Part 4: Steady State Area Under the Concentration-Time Curve of 0 - Last Day (AUCLast, ss) of zanubrutinib
Timepoint [9] 0 0
Predose up to 12 hours postdose
Secondary outcome [10] 0 0
Steady State Maximum Observed Plasma Concentration (Cmax, ss) of Sonrotoclax
Timepoint [10] 0 0
Predose up to 12 hours postdose
Secondary outcome [11] 0 0
Part 3, Part 4: Steady State Maximum Observed Plasma Concentration (Cmax, ss) of zanubrutinib
Timepoint [11] 0 0
Predose up to 12 hours postdose
Secondary outcome [12] 0 0
Steady State Trough Observed Plasma Concentration (Ctrough, ss) of Sonrotoclax
Timepoint [12] 0 0
Predose up to 12 hours postdose
Secondary outcome [13] 0 0
Part 3, Part 4: Steady State Trough Observed Plasma Concentration (Ctrough, ss) of zanubrutinib
Timepoint [13] 0 0
Predose up to 12 hours postdose
Secondary outcome [14] 0 0
Steady State Time to Maximum Plasma Concentration (Tmax, ss) of Sonrotoclax
Timepoint [14] 0 0
Predose up to 12 hours postdose
Secondary outcome [15] 0 0
Part 3, Part 4: Steady State Time to Maximum Plasma Concentration (Tmax, ss) of zanubrutinib
Timepoint [15] 0 0
Predose up to 12 hours postdose
Secondary outcome [16] 0 0
Part 2: AUC of Sonrotoclax administered after a high fat/calorie meal (HF-Fed)
Timepoint [16] 0 0
Predose up to 12 hours postdose
Secondary outcome [17] 0 0
Part 2: Cmax of Sonrotoclax administered after a high fat/calorie meal (HF-Fed)
Timepoint [17] 0 0
Predose up to 12 hours postdose
Secondary outcome [18] 0 0
Part 2, Part 4, Part 6: Overall Response Rate (ORR) as Assessed by the Investigator
Timepoint [18] 0 0
Up to 18 months
Secondary outcome [19] 0 0
Part 2: Major Response Rate (MRR) for WM as Assessed by the Investigator
Timepoint [19] 0 0
Up to 18 months
Secondary outcome [20] 0 0
Part 6: Minimum residual disease (MRD) negativity as measured by next generation sequencing
Timepoint [20] 0 0
Up to 18 months

Eligibility
Key inclusion criteria
Key

* Confirmed diagnosis of one of the following:

NHL Cohorts:

1. MZL i. R/R extranodal, splenic, or nodal MZL defined as disease that relapsed after, or was refractory to, at least one prior therapy ii. Active disease requiring treatment
2. FL i. R/R FL (Grade 1, 2 or 3a based on the WHO 2008 classification of tumors of hematopoietic and lymphoid tissue) and defined as disease that relapsed after, or was refractory to, at least 1 prior systemic therapy
3. DLBCL i. R/R DLBCL (including all subtypes of DLBCL) defined as disease that relapsed after, or was refractory to, at least two prior systemic therapies and has either progressed following or is not a candidate for autologous stem cell transplant (due to comorbidities or non-responsiveness to salvage chemotherapy)
4. Transformed indolent B-cell NHL i. Any lymphoma otherwise eligible for Part 1 that has transformed into a more aggressive lymphoma. Patients with transformation from CLL or SLL (Richter's transformation) are not eligible for Part 1

CLL/SLL Cohorts:
5. CLL/SLL diagnosis that meets the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria i. Disease characterized as Treatment Naive (TN) or R/R disease defined as disease that relapsed after, or was refractory to, at least 1 prior therapy ii. Requiring treatment as defined by history

MCL cohorts:
6. WHO-defined MCL i. R/R MCL defined as disease that relapsed after, or was refractory to, at least 1 prior systemic therapy; ii. Requiring treatment in the opinion of the investigator

WM cohorts:

g. WHO-defined WM (clinical and definitive histologic diagnosis) i. R/R disease defined as disease that relapsed after, or was refractory to, at least 1 prior therapy; ii. Meeting at least 1 criterion for treatment according to consensus panel criteria from the Seventh International Workshop on Waldenström's Macroglobulinemia (Dimopoulos et al 2014)

* Measurable disease by computed tomography (CT)/magnetic resonance imaging (MRI), defined as:

1. CLL: at least 1 lymph node > 1.5 cm in longest diameter and measurable in 2 perpendicular dimensions or clonal lymphocytes measured by flow cytometry
2. DLBCL, FL, MZL, MCL, or SLL: at least 1 lymph node > 1.5 cm in longest diameter OR 1 extranodal lesion > 1.0 cm in the longest diameter, measurable in at least 2 perpendicular dimensions. For MZL, isolated splenomegaly is considered measurable for this study
3. WM: serum immunoglobulin (Ig) M level > 0.5 g/dL
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
* Adequate organ function
* Adequate pancreatic function indicated by:

1. Serum amylase = 1.5 x upper limit of normal (ULN)
2. Serum lipase = 1.5 x ULN

Key
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Known current central nervous system involvement by lymphoma/leukemia
* Known plasma cell neoplasm, prolymphocytic leukemia, history of or currently suspected Richter's syndrome
* Prior therapy = 2 months with or progression on a B-cell lymphoma-2 (Bcl-2) inhibitor

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
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
24/03/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
30/08/2027
Actual
Sample size
Target
Accrual to date
Final
437
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
Concord Repatriation General Hospital - Concord
Recruitment hospital [2] 0 0
Orange Health Service (Central West Cancer Care Centre) - Orange
Recruitment hospital [3] 0 0
Pindara Private Hospital - Benowa
Recruitment hospital [4] 0 0
John Flynn Private Hospital - Tugun
Recruitment hospital [5] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [6] 0 0
Flinders Medical Centre - Bedford PK
Recruitment hospital [7] 0 0
Box Hill Hospital - Box Hill
Recruitment hospital [8] 0 0
Monash Health - Clayton
Recruitment hospital [9] 0 0
St Vincents Hospital Melbourne - Fitzroy
Recruitment hospital [10] 0 0
Peter Maccallum Cancer Centre - Melbourne
Recruitment hospital [11] 0 0
The Alfred Hospital - Melbourne
Recruitment hospital [12] 0 0
Linear Clinical Research - Nedlands
Recruitment postcode(s) [1] 0 0
2139 - Concord
Recruitment postcode(s) [2] 0 0
2800 - Orange
Recruitment postcode(s) [3] 0 0
4217 - Benowa
Recruitment postcode(s) [4] 0 0
4224 - Tugun
Recruitment postcode(s) [5] 0 0
5000 - Adelaide
Recruitment postcode(s) [6] 0 0
5042 - Bedford PK
Recruitment postcode(s) [7] 0 0
3128 - Box Hill
Recruitment postcode(s) [8] 0 0
3168 - Clayton
Recruitment postcode(s) [9] 0 0
3065 - Fitzroy
Recruitment postcode(s) [10] 0 0
3000 - Melbourne
Recruitment postcode(s) [11] 0 0
3004 - Melbourne
Recruitment postcode(s) [12] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Illinois
Country [3] 0 0
United States of America
State/province [3] 0 0
Kansas
Country [4] 0 0
United States of America
State/province [4] 0 0
Massachusetts
Country [5] 0 0
United States of America
State/province [5] 0 0
Minnesota
Country [6] 0 0
United States of America
State/province [6] 0 0
Nebraska
Country [7] 0 0
United States of America
State/province [7] 0 0
New Jersey
Country [8] 0 0
United States of America
State/province [8] 0 0
New York
Country [9] 0 0
United States of America
State/province [9] 0 0
Ohio
Country [10] 0 0
United States of America
State/province [10] 0 0
Pennsylvania
Country [11] 0 0
United States of America
State/province [11] 0 0
Texas
Country [12] 0 0
United States of America
State/province [12] 0 0
Washington
Country [13] 0 0
Germany
State/province [13] 0 0
Dresden
Country [14] 0 0
Italy
State/province [14] 0 0
Milano
Country [15] 0 0
Italy
State/province [15] 0 0
Perugia
Country [16] 0 0
Italy
State/province [16] 0 0
Ravenna
Country [17] 0 0
Italy
State/province [17] 0 0
Roma
Country [18] 0 0
Italy
State/province [18] 0 0
Verona
Country [19] 0 0
New Zealand
State/province [19] 0 0
Auckland
Country [20] 0 0
New Zealand
State/province [20] 0 0
Takapuna
Country [21] 0 0
New Zealand
State/province [21] 0 0
Wellington
Country [22] 0 0
Spain
State/province [22] 0 0
Barcelona
Country [23] 0 0
Spain
State/province [23] 0 0
Madrid
Country [24] 0 0
Spain
State/province [24] 0 0
Pamplona
Country [25] 0 0
Spain
State/province [25] 0 0
Salamanca
Country [26] 0 0
Spain
State/province [26] 0 0
Santander
Country [27] 0 0
United Kingdom
State/province [27] 0 0
Leeds

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
Study Director
Address 0 0
BeiGene
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
[email protected]
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?
BeiGene shares data on completed studies responsibly and provides qualified scientific and medical researchers access to data and supporting documentation for clinical trials in dossiers for medicines and indications after submission and approval in the United States, China, and Europe. Clinical trials supporting subsequent local approvals, new indications, or combination products are eligible for sharing once corresponding regulatory approvals are achieved.

BeiGene shares data only when permitted by applicable data privacy and security laws and regulations, when it is feasible to do so without compromising the privacy of study participants, and other considerations.

Qualified researchers with appropriate competencies who are engaged in novel scientific research may submit a request for participant-level data with a research proposal for BeiGene review. Research teams must include a biostatistician and sign a Data Sharing Agreement prior to receiving access to clinical trial data.

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Clinical study report (CSR)
When will data be available (start and end dates)?
See plan description
Available to whom?
See plan description
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://beigene.com/science/clinical-trials/


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.

Results not provided in https://clinicaltrials.gov/study/NCT04277637