History of Changes for Study: NCT06073821

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

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Study Record Versions

Version	Submitted Date	Changes
1	October 3, 2023	None (earliest Version on record)
2	January 8, 2024	Recruitment Status, Study Status, Contacts/Locations and Oversight
3	January 17, 2024	Contacts/Locations and Study Status
4	February 2, 2024	Study Status and Contacts/Locations
5	April 24, 2024	Study Status and Contacts/Locations

Comparison Format:

Merged
Side-by-Side

Study Identification


Unique Protocol ID:	BGB-11417-301
Brief Title:	Study of Sonrotoclax (BGB-11417) Plus Zanubrutinib (BGB-3111) Compared With Venetoclax Plus Obinutuzumab in Participants With Chronic Lymphocytic Leukemia (CLL)
Official Title:	A Phase 3, Open-Label, Randomized Study of Sonrotoclax (BGB-11417) Plus Zanubrutinib (BGB-3111) Compared With Venetoclax Plus Obinutuzumab in Patients With Previously Untreated Chronic Lymphocytic Leukemia
Secondary IDs:

Study Status


Record Verification:	October 2023
Overall Status:	Not yet recruiting
Study Start:	December 1, 2023
Primary Completion:	February 2032 [Anticipated]
Study Completion:	December 2032 [Anticipated]

First Submitted:	October 3, 2023
First Submitted that Met QC Criteria:	October 3, 2023
First Posted:	October 10, 2023 [Actual]

Last Update Submitted that Met QC Criteria:	October 3, 2023
Last Update Posted:	October 10, 2023 [Actual]

Sponsor/Collaborators


Sponsor:	BeiGene
Responsible Party:	Sponsor
Collaborators:

Oversight


U.S. FDA-regulated Drug:	Yes
U.S. FDA-regulated Device:	No
Data Monitoring:	Yes

Study Description

Brief Summary:

The main objective of this study is to compare the efficacy of sonrotoclax plus zanubrutinib versus venetoclax plus obinutuzumab in participants with chronic lymphocytic leukemia (CLL)

Detailed Description:

Chronic lymphocytic leukemia is a type of blood cancer that affects people around the world. People with CLL suffer from enlarged lymph nodes, spleen, or liver, or have symptoms like night sweats, weight loss and fever. They have shorter life expectancy compared to healthy people. There is an urgent need for new treatment to prolong participant life and control disease-related symptoms.

In this study, participants with CLL, without prior treatment will receive either venetoclax plus obinutuzumab combination treatment that is considered a standard first line treatment or receive sonrotoclax plus zanubrutinib. It is hypothesized that sonrotoclax plus zanubrutinib may be better than venetoclax plus obinutuzumab in treating CLL.

The main purpose of this study is to compare the duration the participants live without the CLL getting worse between participants who received venetoclax plus obinutuzumab versus sonrotoclax plus zanubrutinib. Approximately 640 participants will be included in this study around the world. Participants will have equal chance to be allocated to receive either of the treatment combinations.

Conditions


Conditions:	CLL
Keywords:	CLL Chronic Lymphocytic Leukemia

Study Design


Study Type:	Interventional
Primary Purpose:	Treatment
Study Phase:	Phase 3
Interventional Study Model:	Parallel Assignment
Number of Arms:	2
Masking:	None (Open Label)
Allocation:	Randomized
Enrollment:	640 [Anticipated]

Arms and Interventions

Arms

Assigned Interventions

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

Administered orally

Other Names:

BGB-11417

Drug: Zanubrutinib

Administered orally

Other Names:

BGB-3111

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

Administered orally

Drug: Obinutuzumab

Administered intravenously

Outcome Measures


Primary Outcome Measures:
1.	Progression Free Survival (PFS) [ Time Frame: Up to approximately 9 years ] 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)
Secondary Outcome Measures:
1.	Complete Response Rate (CRR) [ Time Frame: Up to approximately 9 years ] 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.
2.	Rates of Undetectable Measurable Residual Disease [ Time Frame: Up to approximately 9 years ] Undetectable measurable residual disease uMRD4 rate at the first Post- Treatment Follow-up (PTFU 1) Visit will be based on next-generation sequencing.
3.	Overall Survival (OS) [ Time Frame: Up to approximately 9 years ] OS is defined as time from the date of enrollment to the date of death because of any cause
4.	PFS by Investigator Assessment [ Time Frame: Up to approximately 9 years ] FS 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
5.	CRR by Investigator Assessment [ Time Frame: Up to approximately 9 years ] 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
6.	Rates of uMRD4 Based on Flow-Cytometry [ Time Frame: Up to approximately 9 years ] The overall uMRD4 rate is defined as the proportion 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.
7.	Overall Response Rate (ORR) Determined by IRC and Investigator Assessment [ Time Frame: Up to approximately 9 years ] 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).
8.	Duration of Response (DOR) by IRC and Investigator Assessment [ Time Frame: Up to approximately 9 years ] Duration of response (DOR) is defined as the time from first qualifying response PR, PR-L, CR, or CRi) until CLL progression or death.
9.	Number of Participants with Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) [ Time Frame: Up to approximately 9 years ]
10.	The Health-Related Quality of Life (HRQoL) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) [ Time Frame: Up to approximately 9 years ] Global health status (GHS)/qualify of life (QoL) and physical functioning measured by EORTC QLQ-C30 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).
11.	HRQoL) as Assessed by EORTC QLQ-C30 CLL Module Quality of Life Questionnaire - Chronic Lymphocytic Leukemia Module 17 Items (QLQ-CLL17) [ Time Frame: Up to approximately 9 years ] The symptom burden and physical condition/fatigue will be measured by QLQ-CLL17. EORTC QLQ-CLL17 comprises 17 items grouped into 3 multi-item scales: 1) symptom burden, 2) physical condition/fatigue, and 3) worries/fears about health and functioning. The EORTC QLQ-CLL17 will be scored according to the EORTC QLQ-C30 Scoring Manual. An outcome variable consisting of a score from 0 to 100 will be derived for each of the symptom scales, each of the functional scales, and the global measure of health status scale. Higher scores on the global measure of health status and functional scales indicate better health status/function, but higher scores on symptom scales represent greater symptom severity
12.	European Quality of Life 5-Dimensions 5-Levels Health Questionnaire (EQ-5D-5L) [ Time Frame: Up to approximately 9 years ] Mean change from baseline in EQ-5D-5L visual analogue score (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.

Eligibility


Minimum Age:	18 Years
Maximum Age:
Sex:	All
Gender Based:
Accepts Healthy Volunteers:	No
Criteria:	Inclusion Criteria: Treatment-naïve (TN) adults with confirmed diagnosis of CLL which requires treatment Eastern Cooperative Oncology Group (ECOG) score 0, 1, or 2 Measurable disease by Computer Tomography/Magnetic Resonance Imaging Adequate liver function as indicated by aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x the institutional upper limits of normal (ULNs) value; serum total bilirubin < 3.0 x ULN Adequate renal function as defined as creatinine clearance ≥ 50 milliliters per minute Exclusion Criteria: Previous systemic treatment for CLL Known prolymphocytic leukemia or history of, or currently suspected, Richter's transformation Known central nervous system involvement History of confirmed progressive multifocal leukoencephalopathy (PML) Uncontrolled hypertension Note: Other protocol defined criteria may apply

Contacts/Locations


Central Contact Person:	Study Director Telephone: 1-877-828-5568 Email: clinicaltrials@beigene.com
Locations:

IPDSharing


Plan to Share IPD:

References


Citations:
Links:
Available IPD/Information: