A Study to Investigate the Safety of Novel Dose Ramp-up Schedule(s) When Initiating Sonrotoclax in Participants Treated for Blood Cancers.

A Phase 1/2 Open-label Study to Investigate the Safety of Sonrotoclax Ramp-up Schedule(s) in Adult Patients With Hematological Malignancies.

The purpose of this study is to establish the safety of novel dosing and ramp-up schedules for sonrotoclax in participants with hematological malignancies.

Study Overview

• Status: Recruiting
• Conditions: Mantle Cell Lymphoma; Chronic Lymphocytic Leukemia; CLL; MCL
• Intervention / Treatment: Drug: Sonrotoclax; Drug: Zanubrutinib

Detailed Description

This study will test the safety of novel sonrotoclax dosing with gradual increases of sonrotoclax dose over specified periods until the intended target daily dose is reached. The focus will be on tumor lysis syndrome (TLS) and related toxicity signals.

Sonrotoclax is a drug that works by blocking a protein called B-cell lymphoma-2 (BCL-2). When sonrotoclax blocks BCL-2 it slows down or stops the growth of tumor cells and helps them die. This can lead to improvements in patients with certain malignant diseases including chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL). The start of treatment with BCL-2 inhibitor requires a gradual ramp-up over the first weeks to avoid potential consequences of initial tumor cell breakage and the release of cell content in the bloodstream. Several ramp-up schedules have already been explored, and this study aims to optimize the dosing ramp-up schedule that may be beneficial to patients and caregivers. Zanubrutinib is a commercialized product that works by blocking a protein called Bruton's tyrosine kinase (BTK) and controlling the activity and survival of malignant B cells. Zanubrutinib has received approval in over 65 countries/regions worldwide for the treatment of adult participants with B-cell malignancies, including CLL and MCL.

This study will take place at multiple centers worldwide. The overall time to participate in this study is approximately 17 months for treatment-naïve (TN) CLL participants or approximately 32 months for relapsed/refractory (R/R) MCL participants.

• Study Type: Interventional
• Enrollment (Estimated): 258
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Study Director
• Study Contact Backup: Name: Study Director; Phone Number: 1.877.828.5568; Email: clinicaltrials@beonemed.com

Study Locations

• Australia
  • New South Wales
    • Blacktown, New South Wales, Australia, NSW 2148
      • Recruiting
      • Blacktown Cancer and Haematology Centre
  • South Australia
    • Adelaide, South Australia, Australia, SA 5000
      • Recruiting
      • Genesiscare St Andrews
  • Victoria
    • Malvern, Victoria, Australia, VIC 3144
      • Recruiting
      • Cabrini Hospital Malvern
    • Melbourne, Victoria, Australia, VIC 3004
      • Recruiting
      • The Alfred Hospital
  • Western Australia
    • Cooloongup, Western Australia, Australia, WA 6168
      • Recruiting
      • Rockingham Hospital
    • Nedlands, Western Australia, Australia, WA 6009
      • Recruiting
      • Linear Clinical Research
• France
  • Dijon, France, 21000
    • Active, not recruiting
    • CHU Dijon
  • Montpellier, France, 34090
    • Active, not recruiting
    • Chu Montpellier Hopital Saint Eloi
  • Toulouse, France, 31100
    • Active, not recruiting
    • Iuct Oncopole
• United Kingdom
  • Birmingham, United Kingdom, B15 2TH
    • Active, not recruiting
    • Queen Elizabeth Hospital
  • Leeds, United Kingdom, LS9 7TF
    • Active, not recruiting
    • St Jamess University Hospital
• United States
  • Florida
    • Tampa, Florida, United States, 33612-9496
      • Active, not recruiting
      • Moffitt Cancer Center
  • Indiana
    • Fort Wayne, Indiana, United States, 46804
      • Active, not recruiting
      • Fort Wayne Medical Oncology and Hematology
  • Kansas
    • Westwood, Kansas, United States, 66205-2003
      • Active, not recruiting
      • The University of Kansas Cancer Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215-5418
      • Active, not recruiting
      • Dana Farber Cancer Institute
  • Missouri
    • St Louis, Missouri, United States, 63110-1010
      • Active, not recruiting
      • Washington University School of Medicine
  • Washington
    • Seattle, Washington, United States, 98109-4433
      • Active, not recruiting
      • Fred Hutchinson Cancer Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Stable Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2.
2. Adequate organ function and no very recent transfusion or blood growth factor

3. Participants of childbearing potential must be willing to use a highly effective method of birth control and refrain from egg donation for the duration of the study and for ≥ 7 days after the last dose of sonrotoclax or 1 month after the last dose of zanubrutinib, whichever is later.

   Only for participants with Chronic Lymphocytic Leukemia (CLL):

4. Confirmed diagnosis of CLL, based on Hallek et al 2018, and requiring treatment due to certain features of their disease

5. At least 1 measurable lesion based on computed tomography (CT)/magnetic resonance imaging (MRI) and no history of prolymphocytic leukemia or Richter's transformation.

   Only for participants with Mantle cell lymphoma (MCL):

6. Historically confirmed diagnosis of MCL based on the World Health Organization 2022 classification of Haematolymphoid Tumors (WHO-HEAM5) or based on International Consensus Classification (ICC).
7. Relapsed or refractory to the last line of therapy and have received at least 1 prior line of systemic therapy. Note: A line of therapy is considered ≥ 2 consecutive cycles of a systemic anticancer regimen. Patients with prior BTKi therapy should not have progressed during treatment or relapsed within 12 months after BTKi discontinuation.
8. Measurable disease defined as ≥ 1 nodal lesion that is > 1.5 cm in longest diameter, or ≥ 1 extranodal lesion that is > 1 cm in longest diameter.

Exclusion Criteria:

1. Participants unable to comply with the requirements of the protocol
2. Serologic status reflecting active viral hepatitis B virus (HBV) or hepatitis C virus (HCV) infection
3. Positive HIV serology (HIVAb) status unless certain conditions are met.
4. Participants with any major surgical procedure ≤ 28 days before first dose of study treatment
5. Prior systemic treatment for the CLL
6. Uncontrolled autoimmune hemolytic anemia or immune thrombocytopenia requiring treatment
7. Prior exposure to a BCL-2 inhibitor

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arms: 1A,1B and 2A: Zanubrutinib + Sonrotoclax for TN CLL; Participants will receive zanubrutinib alone, followed by a combination with sonrotoclax initiated with a ramp-up according to each schedule defined in the protocol. The total treatment duration is of 15 cycles of 28 days (including the phase of sonrotoclax dose ramp-up)	Drug: Sonrotoclax; Administered orally; Other Names: BGB-11417; Drug: Zanubrutinib; Administered orally; Other Names: BGB-3111
Experimental: Arms: 1C and 2B: Zanubrutinib + Sonrotoclax for R/R MCL; Participants will receive zanubrutinib alone, followed by a combination with sonrotoclax initiated with a ramp-up according to each schedule defined in the protocol, for a total of 27 cycles of 28 days (including the phase of sonrotoclax ramp-up), then will continue on zanubrutinib alone until progression of their disease or other treatment discontinuation criteria.	Drug: Sonrotoclax; Administered orally; Other Names: BGB-11417; Drug: Zanubrutinib; Administered orally; Other Names: BGB-3111

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants who Experience Tumor Lysis Syndrome (TLS)	TLS will be defined by Howard criteria during the schedule-limiting toxicity (SLT) evaluation window	Up to approximately 4 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Adverse Events (AEs)	Safety will be assessed by monitoring and recording of all treatment emergent adverse events (AEs) graded by National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0 and tolerability as determined by protocol-defined Cs during the SLT evaluation window	Up to approximately 4 months
Number of Participants with Dose Modifications During the SLT Evaluation Window		Up to approximately 4 months

Collaborators and Investigators

• Sponsor: BeOne Medicines
• Investigators: Study Director: Study Director, BeOne Medicines

Study record dates

Study Major Dates

• Study Start (Actual): January 23, 2025
• Primary Completion (Estimated): November 30, 2029
• Study Completion (Estimated): November 30, 2032

Study Registration Dates

• First Submitted: November 18, 2024
• First Submitted That Met QC Criteria: November 18, 2024
• First Posted (Actual): November 20, 2024

Study Record Updates

• Last Update Posted (Actual): June 8, 2026
• Last Update Submitted That Met QC Criteria: June 5, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Hematological Malignancies; CLL previously untreated
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Site; Neoplasms; Chronic Disease; Disease Attributes; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Leukemia, B-Cell; Lymphoma; Leukemia, Lymphoid; Leukemia; Pathological Conditions, Signs and Symptoms; Hemic and Lymphatic Diseases; Hematologic Neoplasms; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Mantle-Cell; Tyrosine Kinase Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; zanubrutinib
• Other Study ID Numbers: BGB-11417-108; 2024-518829-15-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

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.

• IPD Sharing Time Frame: See plan description
• IPD Sharing Access Criteria: See plan description
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No