Phase 3 Study of Sonrotoclax with Obinutuzumab or Rituximab vs. Venetoclax with Rituximab in Relapsed/Refractory CLL/SLL Patients
- Trial ID
- 2024-517131-52-00
- Protocol
- BGB-11417-303CLL-RR1
- Sponsor
- BeOne Medicines AG
Trial statistics
Objectives
The primary objective of this study is to compare the efficacy of sonrotoclax plus obinutuzumab versus venetoclax plus rituximab in patients with relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma. 5
Secondary objectives include:
- Comparing the efficacy of sonrotoclax plus rituximab versus venetoclax plus rituximab as measured by progression-free survival.
- Evaluating the efficacy of sonrotoclax plus obinutuzumab versus venetoclax plus rituximab based on the undetectable minimal residual disease rate at cycle 14 day 1, complete response or complete response with incomplete hematopoietic recovery, and overall survival.
- Comparing efficacy between various treatment arms, including sonrotoclax plus obinutuzumab versus sonrotoclax plus rituximab and sonrotoclax plus obinutuzumab MRD-guided versus venetoclax plus rituximab.
- Assessing combination treatment efficacy through overall response rate, duration of response, time to response, and time to next treatment.
- Monitoring the rate of undetectable minimal residual disease at multiple timepoints.
- Measuring changes in disease- and treatment-specific symptoms and function via patient-reported outcomes.
- Evaluating the safety and tolerability of the treatments.
Participants
The study involves a total of 344 participants diagnosed with relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma. The study population includes both male and female individuals within specific age ranges. Eligible participants must be aged 18 years or older and have received at least one prior therapy for the condition, consisting of a minimum of two cycles per line of treatment. Inclusion requires an Eastern Cooperative Oncology Group performance status of 0, 1, or 2. Specific physiological requirements include adequate marrow function, characterized by defined limits for absolute neutrophil count, platelet counts, and hemoglobin levels. Additionally, participants must demonstrate adequate liver function and renal function, with a life expectancy exceeding 6 months.
Plans and Procedures
This Phase 3, randomized, open-label, multicenter study is designed to evaluate the efficacy of sonrotoclax in combination with anti-CD20 antibody therapies compared to venetoclax plus rituximab. The study targets patients with relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma. The primary endpoint is progression-free survival, as determined by a blinded independent review committee. Secondary endpoints include overall survival, complete response rate, overall response rate, and the rate of undetectable minimal residual disease. The research methodology involves a screening visit to confirm eligibility based on specific clinical criteria, followed by treatment and various follow-up visits to monitor clinical outcomes, safety, and quality of life. The total duration of the study is expected to extend until December 31, 2031.
Treatment
BGB-11417 is administered as an oral film-coated tablet at a dosage of 320 mg.
Venetoclax is administered via oral film-coated tablets at a dosage of 400 mg.
Rituximab is administered as a solution for infusion via intravenous infusion at a dosage of 500 mg/m2.
Obinutuzumab is administered as a solution for infusion via intravenous infusion at a dosage of 1,000 mg.
Efficacy
The primary efficacy endpoint is progression-free survival (PFS), defined as the interval from the date of randomization to the date of disease progression, as determined by a blinded independent review committee (BIRC), or death, whichever occurs first. Secondary efficacy assessments include the complete response rate (CRR), representing the proportion of patients achieving a best response of complete response (CR) or complete response with incomplete hematologic recovery (CRi) as determined by the BIRC or investigator assessment. Other evaluated parameters include overall survival (OS), overall response rate (ORR), duration of response (DOR), time to response (TTR), and time to next treatment (TTNT).
The rate of undetectable minimal residual disease at < 10-4 sensitivity (uMRD4) in peripheral blood will be assessed using next-generation sequencing (NGS) via clonoSEQ at various timepoints, including C8D1, C11D1, C14D1, C20D1, post-treatment follow-up (PTFU1), and subsequent follow-up. Patient-reported outcomes will be evaluated using the EORTC-QLQ-C30 to measure global health status and physical functioning, and the EORTC QLQ-CLL17 to assess symptom burden and fatigue.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Patients aged ≥ 18 years with a confirmed diagnosis of CLL/SLL, per the iwCLL 2018 criteria (Hallek et al 2018).
- Patients must have ≥ 1 prior therapy for CLL/SLL. For each line of therapy, patients must receive at least 2 cycles of this therapy.
- For patients who received a BCL2i, only those with CLL/SLL who received BCL2i in the first line setting with fixed duration therapy, have a remission for ≥ 3 years, and have a time interval of ≥ 2 years from the last dose of BCL2i to screening, are eligible. Patients should be informed about their options to choose other approved CLL/SLL therapies in this setting.
- Indications for CLL/SLL therapy are met by one of the criteria per the iwCLL 2018 criteria, with minor modification as discussed in the main protocol.
- Eastern Cooperative Oncology Group (ECOG) Performance status 0, 1, or 2.
- Adequate marrow function as defined by: – Absolute neutrophil count ≥ 1.0 x 109 cells/L with an exception for patients with bone marrow involvement, in which case the absolute neutrophil count must be ≥ 0.75 x 109 cells/L (without growth factor support within the past 7 days). – Platelet counts ≥ 75 x 109 cells/L; in cases of thrombocytopenia clearly due to marrow involvement of CLL (per the discretion of the investigator), the platelet count should be ≥ 30 x 109 cells/L (without growth factor support or transfusion within the past 7 days). – Hemoglobin > 75 g/L (may be posttransfusion).
- Adequate liver function as indicated by aspartate aminotransferase and alanine aminotransferase ≤ 2.5 x upper limits of normal (ULNs) value; serum total bilirubin ≤ 1.5 x ULNs (unless documented Gilbert syndrome where total bilirubin ≤ 3 x ULNs).
- Adequate renal function, defined by a value ≥ 30 mL/min, determined either by creatinine clearance directly measured with a 24-hour urine collection or via estimated glomerular filtration rate calculated according to the Chronic Kidney Disease Epidemiology Collaboration equation.
- Life expectancy > 6 months.
Exclusion Criteria
- No active infection including hepatitis B or C virus or HIV at the time of study treatment initiation.
- No active prolymphocytic leukemia or currently suspected Richter’s transformation at the time of consideration for study.
- No ongoing clinically significant cardiovascular or pulmonary disease that prevents participation.
- No central nervous system involvement by CLL/SLL.
- No history of prior or active malignancy within 18 months, except for conditions as listed below and as long as patients have recovered from the acute side effects incurred because of previous therapy: – Adequately treated nonmelanoma skin cancer or lentigo maligna without evidence of disease. – Adequately treated cervical carcinoma in situ without evidence of disease. – Localized prostate cancer with Gleason score ≤ 6 or controlled prostate cancer with androgen deprivation treatment. – Treated early-stage breast cancer with or without hormonal therapy.
- No other active antineoplastic treatment.
- No CYP3A4 moderate or strong inhibitors or CYP3A4 moderate or strong inducers.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Austria | Recruiting | 15 Dec 2025 | 13 |
 Belgium | Recruiting | 15 Dec 2025 | 9 |
 Czechia | Recruiting | 15 Dec 2025 | 22 |
 Denmark | Recruiting | 15 Dec 2025 | 14 |
 France | Recruiting | 15 Dec 2025 | 39 |
 Germany | Recruiting | 15 Dec 2025 | 45 |
 Ireland | Recruiting | 15 Dec 2025 | 19 |
 Italy | Recruiting | 15 Dec 2025 | 34 |
 The Netherlands | Recruiting | 15 Dec 2025 | — |
 Poland | Recruiting | 15 Dec 2025 | 27 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Venclyxto 10 mg film-coated tablets | Test | FILM-COATED TABLETS | ORAL | 400 | 100 | PRD6353818 |
Venclyxto 100 mg film-coated tablets | Test | FILM-COATED TABLETS | ORAL | 400 | 100 | PRD6353834 |
BGB-11417 | Test | FILM-COATED TABLET | ORAL | 320 | 100 | PRD9450024 |
MabThera 100 mg concentrate for solution for infusion | Test | CONCENTRATE FOR SOLUTION FOR INFUSION | INTRAVENIOUS INFUSION | 500 | 24 | PRD2154041 |
BGB-11417 | Test | FILM-COATED TABLET | ORAL | 320 | 100 | PRD9450025 |
BGB-11417 | Test | FILM-COATED TABLET | ORAL | 320 | 100 | PRD9450022 |
Gazyvaro 1,000 mg concentrate for solution for infusion. | Test | CONCENTRATE FOR SOLUTION FOR INFUSION | INTRAVENIOUS INFUSION | 1000 | 24 | PRD1753415 |
BGB-11417 | Test | FILM-COATED TABLET | ORAL | 320 | 100 | PRD9450023 |
MabThera 500 mg concentrate for solution for infusion | Test | CONCENTRATE FOR SOLUTION FOR INFUSION | INTRAVENIOUS INFUSION | 500 | 24 | PRD2154043 |
Venclyxto 50 mg film-coated tablets | Test | FILM-COATED TABLETS | ORAL | 400 | 100 | PRD6353826 |