Mature B-Cell MalignanciesPhase 1NCT04277637
Study of Bcl-2 Inhibitor Sonrotoclax (BGB-11417) in Participants With Mature B-Cell Malignancies
A Phase 1 study testing Sonrotoclax, Zanubrutinib and Obinutuzumab in people with Mature B-Cell Malignancies, run by BeOne Medicines at 43 sites in 7 countries.
Trial summary
The purpose of this study is to determine the safety, tolerability; and to define the maximum tolerated dose (MTD) and Recommended Phase 2 Dose (RP2D); and to evaluate the safety and tolerability of the ramp-up dosing schedule and at the RP2D of BGB-11417 monotherapy, and when given in combination with zanubrutinib… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Mature B-Cell Malignancies
- What is being tested?
- Sonrotoclax, Zanubrutinib and Obinutuzumab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 437 participants
- Where
- 43 sitesin 7 countries
- Study dates
- 24 Mar 2020to 31 May 2027
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Confirmed diagnosis of one of the following:
- NHL Cohorts:
- 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
- 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
- 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)
- 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
Show all 21Show fewer
- CLL/SLL Cohorts:
- 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:
- 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:
- 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:
- 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
- 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
- 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:
- Serum amylase ≤ 1.5 x upper limit of normal (ULN)
- Serum lipase ≤ 1.5 x ULN
Who cannot join
- 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.
Trial locations and contacts
43 sites in 7 countries.
43 sites in 7 countries
United States13 sites
Massachusetts General Hospital
Boston, Massachusetts, 02114
Northwestern University
Chicago, Illinois, 60611
The James Cancer Hospital and Solove Research Institute At Ohio State University
Columbus, Ohio, 43210-1240
John Theurer Cancer Center Hackensack University Medical Center
Hackensack, New Jersey, 07601
Md Anderson Cancer Center
Houston, Texas, 77030-3907
University of Kansas Medical Center Research Institute
Kansas City, Kansas, 66160-8500
UCLA Hematologyoncology
Los Angeles, California, 90095-3075
Columbia University Medical Center
New York, New York, 10032
Memorial Sloan Kettering Cancer Center Mskcc
New York, New York, 10065-6800
University of Nebraska Medical Center
Omaha, Nebraska, 68198
Upmc Hillman Cancer Center(Univ of Pittsburgh)
Pittsburgh, Pennsylvania, 15232-1309
Mayo Clinic Rochester
Rochester, Minnesota, 55905-0001
Fred Hutchinson Cancer Research Center
Seattle, Washington, 98109-4433
Australia12 sites
Royal Adelaide Hospital
Adelaide, South Australia, SA 5000
Flinders Medical Centre
Bedford PK, South Australia, SA 5042
Pindara Private Hospital
Benowa, Queensland, QLD 4217
Box Hill Hospital
Box Hill, Victoria, VIC 3128
Monash Health
Clayton, Victoria, VIC 3168
Concord Repatriation General Hospital
Concord, New South Wales, NSW 2139
St Vincents Hospital Melbourne
Fitzroy, Victoria, VIC 3065
Peter Maccallum Cancer Centre
Melbourne, Victoria, VIC 3000
The Alfred Hospital
Melbourne, Victoria, VIC 3004
Linear Clinical Research
Nedlands, Western Australia, WA 6009
Orange Health Service (Central West Cancer Care Centre)
Orange, New South Wales, NSW 2800
John Flynn Private Hospital
Tugun, Queensland, QLD 4224
Spain7 sites
Vall D Hebron Institute of Oncology Vhio
Barcelona, 08035
Hospital Clinic de Barcelona
Barcelona, 08036
Hospital de La Santa Creu I Sant Pau
Barcelona, 08041
Ico H Duran I Reynals
Barcelona, 08907
Start Madrid Fundacion Jimenez Diaz
Madrid, 28040
Hospital Universitario de Salamanca
Salamanca, 37007
Hospital Universitario Marques de Valdecilla
Santander, 39008
Italy6 sites
Ospedale San Raffaele
Milan, 20132
Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda
Milan, 20162
Ospedale Santa Maria Della Misericordia
Perugia, 6129
Azienda Unita Sanitaria Locale Di Ravenna
Ravenna, 48121
Fondazione Policlinico Universitario Agostino Gemelli
Roma, 00168
Centroricerche Cliniche Di Verona Srl
Verona, 37134
New Zealand3 sites
North Shore Hospital
Auckland, 0622
Auckland City Hospital
Auckland, 1023
Wellington Regional Hospital (Ccdhb)
Wellington, 6021
Germany1 site
Universitatsklinikum Carl Gustav Carus An Der Technischen Universitat Dresden
Dresden, 01307
United Kingdom1 site
The Leeds Teaching Hospitals Nhs Trust
Leeds, LS9 7TF
About this study
Official 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
The purpose of this study is to determine the safety, tolerability; and to define the maximum tolerated dose (MTD) and Recommended Phase 2 Dose (RP2D); and to evaluate the safety and tolerability of the ramp-up dosing schedule and at the RP2D of BGB-11417 monotherapy, and when given in combination with zanubrutinib and obinutuzumab.
Read the detailed description
Our company, previously known as BeiGene, is now officially BeOne Medicines. Because some of our older studies were sponsored under the name BeiGene, you may see both names used for this study on this website.
- Conditions
- Mature B-Cell Malignancies
- Being tested
- Sonrotoclax, Zanubrutinib, Obinutuzumab
- Keywords
- NHL, BCL2 Inhibitor, CLL, MCL, MZL, SLL, WM, Bcl-2i, BTKi
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SonrotoclaxDrug
Also called BGB-11417
Film-coated tablets administered once daily at a dose as specified in the treatment arm
ZanubrutinibDrug
Also called BGB-3111
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)
ObinutuzumabDrug
Given as an intravenous infusion administered per label.
| Study group | Role | What they receive |
|---|---|---|
| Sonrotoclax Monotherapy Dose Finding: Part 1 | Experimental | 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. Receives: Drug: Sonrotoclax |
| Sonrotoclax Monotherapy Expansion Cohorts: Part 2 | Experimental | 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. Receives: Drug: Sonrotoclax |
| Sonrotoclax + Zanubrutinib Combination Therapy Dose Finding: Part 3 | Experimental | Participants with R/R MCL, R/R or treatment-naïve (TN) CLL/SLL will receive oral sonrotoclax in combination with zanubrutinib. Receives: Drug: Sonrotoclax; Drug: Zanubrutinib |
| Sonrotoclax + Zanubrutinib Combination Therapy Dose Expansion: Part 4 | Experimental | 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. Receives: Drug: Sonrotoclax; Drug: Zanubrutinib |
| Sonrotoclax + Zanubrutinib Combination Therapy Dose Escalation: Part 5 | Experimental | Participants with treatment naïve CLL/SLL will receive oral sonrotoclax in combination with obinutuzumab without and with zanubrutinib. Receives: Drug: Sonrotoclax; Drug: Zanubrutinib; Drug: Obinutuzumab |
| Sonrotoclax + Zanubrutinib Combination Therapy Dose Expansion: Part 6 | Experimental | 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. Receives: Drug: Sonrotoclax; Drug: Zanubrutinib; Drug: Obinutuzumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants Experiencing Treatment Emergent Adverse Events (TEAEs)
Measured: Up to 30 days after the last dose of study drug, an average of 18 months
Number of Participants Experiencing Serious Adverse Events (SAEs)
Measured: Up to 30 days after the last dose of study drug, an average of 18 months
Number of Participants Experiencing Adverse Events (AEs) leading to discontinuation of Sonrotoclax
Measured: Up to 30 days after the last dose of study drug, an average of 18 months
Part 1, Part 3: Maximum Tolerated Dose (MTD) of Sonrotoclax
Measured: Up to approximately 2 months
Part 1, Part 3, Part 5: RP2D of Sonrotoclax
Measured: Day 1 to last dose of study drug, an average of 18 months
Part 1, Part 3, Part 5: Number of participants experiencing tumor lysis syndrome (TLS) relevant events
Measured: Up to 30 days after the last dose of study drug, an average of 18 months
Part 1, Part 3, Part 5: Number of Participants Experiencing Dose-Limiting Toxicities (DLTs
Measured: Up to approximately 2 months
Secondary outcomes (20)
Maximum Observed Plasma Concentration (Cmax) After a Single Dose of Sonrotoclax
Measured: Predose up to 12 hours postdose
Area Under the Concentration-Time Curve from Time 0 to the Last Quantifiable Concentration (AUC0-last) After a Single Dose of Sonrotoclax
Measured: Predose up to 12 hours postdose
Area Under the Concentration-Time Curve from Time 0 to Infinity (AUC0-∞) After a Single Dose of Sonrotoclax
Measured: Predose up to 12 hours postdose
Time Taken for Half the Initial Dose Administered to Be Eliminated from The Body (T1/2) of Sonrotoclax
Measured: Predose up to 12 hours postdose
Time to Maximum Plasma Concentration (Tmax) After a Single Dose of Sonrotoclax
Measured: Predose up to 12 hours postdose
Apparent Clearance (CL/F) After a Single Dose of Sonrotoclax
Measured: Predose up to 12 hours postdose
Apparent volume of distribution (Vz/F) After a Single Dose of Sonrotoclax
Measured: Predose up to 12 hours postdose
Steady State Area Under the Concentration-Time Curve of 0 - Last Day (AUCLast, ss) of Sonrotoclax
Measured: Predose up to 12 hours postdose
Part 3, Part 4: Steady State Area Under the Concentration-Time Curve of 0 - Last Day (AUCLast, ss) of zanubrutinib
Measured: Predose up to 12 hours postdose
Steady State Maximum Observed Plasma Concentration (Cmax, ss) of Sonrotoclax
Measured: Predose up to 12 hours postdose
Part 3, Part 4: Steady State Maximum Observed Plasma Concentration (Cmax, ss) of zanubrutinib
Measured: Predose up to 12 hours postdose
Steady State Trough Observed Plasma Concentration (Ctrough, ss) of Sonrotoclax
Measured: Predose up to 12 hours postdose
Part 3, Part 4: Steady State Trough Observed Plasma Concentration (Ctrough, ss) of zanubrutinib
Measured: Predose up to 12 hours postdose
Steady State Time to Maximum Plasma Concentration (Tmax, ss) of Sonrotoclax
Measured: Predose up to 12 hours postdose
Part 3, Part 4: Steady State Time to Maximum Plasma Concentration (Tmax, ss) of zanubrutinib
Measured: Predose up to 12 hours postdose
Part 2: AUC of Sonrotoclax administered after a high fat/calorie meal (HF-Fed)
Measured: Predose up to 12 hours postdose
Part 2: Cmax of Sonrotoclax administered after a high fat/calorie meal (HF-Fed)
Measured: Predose up to 12 hours postdose
Part 2, Part 4, Part 6: Overall Response Rate (ORR) as Assessed by the Investigator
ORR is defined as the proportion of participants who had confirmed complete response Complete Response (CR) or Partial Response (PR)
Measured: Up to 18 months
Part 2: Major Response Rate (MRR) for WM as Assessed by the Investigator
Measured: Up to 18 months
Part 6: Minimum residual disease (MRD) negativity as measured by next generation sequencing
Measured: Up to 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Feb 2020
- Study start24 Mar 2020
- Primary completion31 May 2027 (estimated)
- Study completion31 May 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Mature B-Cell MalignanciesStudies of the same condition, open and under way.
- More trials run by BeOne MedicinesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 437 participants (actual)
Sponsor and investigators
- Lead sponsor
- BeOne Medicines
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Study Director, Study director, BeOne Medicines
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04277637
- Sponsor's protocol ID
- BGB-11417-101
- Other IDs
- 2024-515592-35-00, 2020-004641-37
- Status last verified
- Jun 2026
- First submitted
- 18 Feb 2020
- Last updated
- 22 Jun 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: BeOne 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. BeOne 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 BeOne review. Research teams must include a biostatistician and sign a Data Sharing Agreement prior to receiving access to clinical trial data.