Study of Sonrotoclax (BGB-11417) Plus Zanubrutinib (BGB-3111) Compared With Venetoclax Plus Obinutuzumab in Participants With Chronic Lymphocytic Leukemia (CLL)

Browse trials for

• Leukemia, Lymphocytic, Chronic, B-Cell 1,603

Keywords

• CLL
• Chronic Lymphocytic Leukemia

Leukemia, Lymphocytic, Chronic, B-Cell

1,603 studies on the registry are indexed under Leukemia, Lymphocytic, Chronic, B-Cell; 243 are open to participants now.

This study's planned enrollment of 652 is above the median of 40 across 1,325 interventional studies indexed under Leukemia, Lymphocytic, Chronic, B-Cell.

Lead sponsor

BeOne Medicines is the lead sponsor of 61 studies on the registry; 42 are open to participants now.

Of its 6 completed or terminated interventional studies of FDA-regulated products, 0 (0%) have results posted.

Study arms

• Experimental
  Sonrotoclax Plus Zanubrutinib

  Participants will receive from start of Cycle 1 a standard dose of zanubrutinib once or twice daily orally and in combination with sonrotoclax starting from Cycle 4 onwards at increasing doses until target dose is reached and continuing until end of Cycle 15 (each cycle is 28 days)

  Drug: Sonrotoclax · Drug: Zanubrutinib

• Active comparator
  Venetoclax Plus Obinutuzumab

  Participants will receive obinutuzumab 100mg intravenously on Day 1 Cycle 1, followed by 900 mg on Day 2 Cycle 1 (or alternatively receive 1000 mg intravenously on Day 1), followed by 1000 mg on Days 8 and 15 of Cycle 1 and thereafter on Day 1 of Cycles 2 through 6 (each cycle is 28 days) in combination with venetoclax at increasing doses until target dose is reached from Day 22 Cycle 1 until end of Cycle 12 (each cycles is 28 days)

  Drug: Venetoclax · Drug: Obinutuzumab

Interventions

• DrugSonrotoclax

  Administered orally

  Also known as: BGB-11417

• DrugZanubrutinib

  Administered orally

  Also known as: BGB-3111

• DrugVenetoclax

  Administered orally

• DrugObinutuzumab

  Administered intravenously

Primary outcomes

1. Cohort 1: Progression Free Survival (PFS）

   PFS is defined as the time from the date of enrollment to the date of first confirmed disease progression or death due to any cause, whichever occurs first, as determined by independent review committee (IRC)

   Time frame: Up to approximately 9 years

2. Cohort 1: Rate of Undetectable Measurable Residual Disease

   Undetectable measurable residual disease uMRD4 rate at the first Post- Treatment Follow-up (PTFU 1) Visit will be based on next-generation sequencing.

   Time frame: Up to one and a half years

Secondary outcomes

1. Cohort 1: Overall Survival (OS)

   OS is defined as time from the date of enrollment to the date of death because of any cause

   Time frame: Up to approximately 9 years

2. Cohort 1: Complete Response Rate (CRR ) by IRC

   CRR is defined as the percentage of participants that achieved best response of complete response (CR)/ complete response with incomplete hematopoietic recovery (CRi), determined by IRC.

   Time frame: Up to approximately 9 years

3. Cohort 1: PFS by Investigator Assessment

   PFS is defined as the time from the date of enrollment to the date of first confirmed disease progression or death due to any cause, whichever occurs first, as determined by investigator assessment

   Time frame: Up to approximately 9 years

4. Cohort 1: CRR by Investigator Assessment

   CRR is defined as the percentage of participants that achieved best response of complete response (CR)/ complete response with incomplete hematopoietic recovery (CRi), determined by Investigator Assessment

   Time frame: Up to approximately 9 years

5. Cohort 1: Rate of Undetectable Measurable Residual Disease

   The overall uMRD4 rate is defined as the percentage of participants who achieve uMRD status in peripheral blood before disease progression or start of new anti-CLL treatment (whichever is earlier), based on flow cytometry.

   Time frame: Up to approximately 9 years

6. Cohort 1: Overall Response Rate (ORR) by IRC and Investigator Assessment

   ORR is defined as the percentage of participants who achieve a response (CR, CRi, nodular partial remission (nPR), partial response (PR), and partial response with lymphocytosis \[PR-L\]), before disease progression or start of new anti-CLL treatment (whichever is earlier).

   Time frame: Up to approximately 9 years

7. Cohort 1: Duration of Response (DOR) by IRC and Investigator Assessment

   DOR is defined as the time from first qualifying response PR, PR-L, CR, or CRi) until CLL progression or death.

   Time frame: Up to approximately 9 years

8. Pooled Cohorts: PFS by IRC and Investigator Assessment

   PFS is defined as the time from the date of enrollment to the date of first confirmed disease progression or death due to any cause, whichever occurs first, as determined by IRC

   Time frame: Up to approximately 9 years

9. Pooled Cohorts: ORR by IRC and Investigator Assessment

   ORR is defined as the percentage of participants who achieve a response (CR, CRi, nodular partial remission (nPR), partial response (PR), and partial response with lymphocytosis \[PR-L\]), before disease progression or start of new anti-CLL treatment （whichever is earlier）.

   Time frame: Up to approximately 9 years

10. Pooled Cohorts: DOR by IRC and Investigator Assessment

    DOR is defined as the time from first qualifying response PR, PR-L, CR, or CRi) until CLL progression or death.

    Time frame: Up to approximately 9 years

11. Pooled Cohorts: Rate of Undetectable Measurable Residual Disease

    The overall uMRD4 rate is defined as the percentage of participants who achieve uMRD status in peripheral blood before disease progression or start of new anti-CLL treatment (whichever is earlier),based on next-generation sequencing.

    Time frame: Up to approximately 9 years

12. Pooled Cohorts: CRR by IRC and Investigator Assessment

    CRR is defined as the percentage of participants that achieved best response of complete response (CR)/ complete response with incomplete hematopoietic recovery (CRi), determined by Investigator Assessment

    Time frame: Up to approximately 9 years

13. Cohort 1 and Pooled Cohorts: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)

    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

    Time frame: Up to one and a half years for Sonrotoclax Plus Zanubrutinib group and 13 months for Venetoclax Plus Obinutuzumab group]

14. Cohort 1 and Pooled Cohorts: Change from baseline in European Organization for Research and Treatment of Cancer Quality of Life Cancer Questionnaire -Core 30 (EORTC QLQ-C30) Global Health Status/QoL (GHS) and Physical Functioning Scales

    The EORTC QLQ-30 contains 30 questions that incorporate 5 functional scales (physical functioning, role functioning, emotional functioning, cognitive functioning, and social functioning), 1 global health status scale, 3 symptom scales (fatigue, nausea and vomiting, and pain), and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The participant answers questions about their health during the past week. There are 28 questions answered on a 4-point scale where 1 =Not at all (best) to 4 =Very Much (worst) and 2 questions answered on a 7-point scale where 1 =Very poor (worst) to 7 =Excellent (best). Higher scores in GHS and functional scales indicate better quality of life.

    Time frame: Every three cycles during the treatment period

15. Cohort 1 and Pooled Cohorts: Change from baseline in EORTC Quality of Life Questionnaire - Chronic Lymphocytic Leukemia Module 17 Items (QLQ-CLL17) Symptom Burden and Physical Condition Scales

    The symptom burden and physical condition/fatigue will be measured by EQ-5D-5L. EQ-5D-5L is a standardized instrument that measures health-related quality of life for men with prostate cancer. EQ-5D consists of EQ-5D descriptive system and EQ visual analogue scale (VAS). EQ-5D descriptive system comprises of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems, and 5=extreme problems. Number of participants with various responses to the mobility questionnaire are reported.

    Time frame: Every three cycles during the treatment period

16. Cohort 1 and Pooled Cohorts: Change from baseline in European Quality of Life 5-Dimensions 5-Levels Health Questionnaire （EQ-5D-5L) Visual Analogue Scale (VAS).

    Mean change from baseline in EQ-5D-5L VAS. The EQ-5D-5L measures health outcomes using a VAS to record a participant's self-rated health on a scale from 0 to 100, where 100 is 'the best health you can imagine' and 0 is 'the worst health you can imagine. A higher score indicates better health outcomes.

    Time frame: Every three cycles during the treatment period

Individual participant data

Plan to share: 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.

Supporting information: Study protocol, Sap, Csr