A Study to Investigate Progression-Free Survival With Sonrotoclax Plus Obinutuzumab Or Sonrotoclax Plus Rituximab Compared With Venetoclax Plus Rituximab Treatment In Patients With Relapsed and/or Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

Overview

Sponsor-declared trial summary

Key facts

Sponsor

BeOne Medicines AG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

3 Nov 2025 → ongoing

Decision date (initial)

2025-09-29

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

BeiGene Ltd.

External identifiers

EU CT number

2024-517131-52-00

ClinicalTrials.gov

NCT06943872

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

The primary objective of this study is to compare the efficacy of sonrotoclax plus
obinutuzumab versus venetoclax plus rituximab in patients with relapsed and/or
refractory (R/R) chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL).

Secondary objectives 10

1. To compare the efficacy between Arm B (sonrotoclax plus rituximab) versus Arm D (venetoclax plus rituximab) as measured by PFS.
2. To compare the efficacy between Arm A (sonrotoclax plus obinutuzumab) versus Arm D (venetoclax plus rituximab) as measured by the uMRD rate at C14D1, complete response/complete response with incomplete hematopoietic recovery (CR/CRi), and overall survival (OS).
3. To compare the efficacy of Arm B (sonrotoclax plus rituximab) versus Arm D (venetoclax plus rituximab).
4. To evaluate the efficacy between Arm A (sonrotoclax plus obinutuzumab) versus Arm B (sonrotoclax plus rituximab).
5. To evaluate the efficacy between Arm A (sonrotoclax plus obinutuzumab) versus Arm D (venetoclax plus rituximab).
6. To evaluate the efficacy between Arm C (sonrotoclax plus obinutuzumab MRD-guided) versus Arm D (venetoclax plus rituximab).
7. To evaluate the efficacy of combination treatments in all arms in terms of overall response rate (ORR), duration of response (DOR), and time to response (TTR), time to next anti-CLL/SLL treatment (TTNT)
8. To evaluate the rate of uMRD at various timepoints in all arms
9. To measure changes in the patient-reported disease- and treatment-specific symptoms and function and to compare the differences between Arm A (sonrotoclax plus obinutuzumab) versus Arm D (venetoclax plus rituximab), between Arm B (sonrotoclax plus rituximab) versus Arm D (venetoclax plus rituximab), between Arm C (sonrotoclax plus obinutuzumab MRD-guided) versus Arm D (venetoclax plus rituximab), between Arm A (sonrotoclax plus obinutuzumab) versus Arm B (sonrotoclax plus rituximab)
10. To evaluate the safety and tolerability of treatment in all arms

Conditions and MedDRA coding

Relapsed/Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

Yes

IPD plan description

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, and shared when it is feasible to do so without compromising the privacy of study participants. Qualified researchers with appropriate competencies who are engaged in novel scientific research may submit a request for participant-level data along 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.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Patients aged ≥ 18 years with a confirmed diagnosis of CLL/SLL, per the iwCLL 2018 criteria (Hallek et al 2018).
2. Patients must have ≥ 1 prior therapy for CLL/SLL. For each line of therapy, patients must receive at least 2 cycles of this therapy.
3. 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.
4. 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.
5. Eastern Cooperative Oncology Group (ECOG) Performance status 0, 1, or 2.
6. 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).
7. 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).
8. 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.
9. Life expectancy > 6 months.

Exclusion criteria 7

1. No active infection including hepatitis B or C virus or HIV at the time of study treatment initiation.
2. No active prolymphocytic leukemia or currently suspected Richter’s transformation at the time of consideration for study.
3. No ongoing clinically significant cardiovascular or pulmonary disease that prevents participation.
4. No central nervous system involvement by CLL/SLL.
5. 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.
6. No other active antineoplastic treatment.
7. No CYP3A4 moderate or strong inhibitors or CYP3A4 moderate or strong inducers.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. PFS, defined as the time from the date of randomization to the date of disease progression as determined by the blinded independent review committee (BIRC) or death, whichever occurs first.

Secondary endpoints 11

1. PFS, defined as the time from the date of randomization to the date of disease progression as determined by the BIRC or death, whichever occurs first.
2. • Undetectable minimal residual disease at < 10-4 sensitivity (uMRD4) rate in peripheral blood at C14D1 Visit based on next-generation sequencing (NGS [clonoSEQ]). • Complete response rate (CRR), defined as the proportion of patients that achieve a best response of CR or CRi (CR/CRi), as determined by the BIRC. • OS, defined as the time from the date of randomization to the date of death.
3. • PFS per investigator assessment. • CRR per the BIRC and investigator assessment. • OS. • Rate of uMRD4 (C8D1, C11D1, C14D1, and Posttreatment follow-up [PTFU]1) based on NGS (clonoSEQ).
4. • PFS per BIRC and investigator assessment. • CRR per BIRC and investigator assessment. • OS. • Rate of uMRD4 (C8D1, C11D1, C14D1, and PTFU1) based on NGS (clonoSEQ).
5. • Rate of uMRD4 (C8D1, C11D1 and PTFU1) based on NGS (clonoSEQ). • CRR per investigator assessment. • PFS per investigator assessment.
6. • PFS per investigator assessment. • CRR per investigator assessment. • OS. • Rate of uMRD4 (C8D1, C11D1, C14D1, and PTFU1) based on NGS (clonoSEQ).
7. • ORR, defined as the proportion of patients that achieve a best response of partial response (PR) or better, as determined by the BIRC and investigator assessment. • DOR, defined as the time from the date that response criteria were first met to the date of first documentation of disease progression or death, whichever occurred first per the BIRC and investigator assessment.
8. • TTR, defined as the time from the date of randomization to the date response criteria were first met, per the BIRC and investigator assessment. • TTNT, defined as the time from the date of randomization to the date of next anti-CLL/SLL treatment. (The BIRC assessments are applicable for Arms A, B, and D only.)
9. Rate of uMRD4 in peripheral blood at C8D1, C11D1, C14D1, C20D1, PTFU1, and subsequent follow-up timepoints
10. Global health status/QoL and physical functioning as measured by EORTC-QLQ-C30 and Symptom burden due to disease or treatment (symptom burden) and physical condition/fatigue (fatigue) as measured by EORTC QLQ-CLL17.
11. Safety (adverse events, serious adverse events, changes from baseline in clinical laboratory tests, physical examinations, and vital signs).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 10

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

BeOne Medicines AG

Sponsor organisation

BeOne Medicines AG

Address

Aeschengraben 27

City

Basel

Postcode

4051

Country

Switzerland

Scientific contact point

Organisation

BeOne Medicines AG

Contact name

BeOne Medical Officer

Public contact point

Organisation

BeOne Medicines AG

Contact name

BeOne Medical Officer

Third parties 15

Locations

12 EU/EEA countries · 69 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 166 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

7 submissions — initial application plus substantial / non-substantial modifications