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

• ClinicalTrials.gov Identifier: NCT06073821
• Recruitment Status: Recruiting
• First Posted: October 10, 2023
• Last Update Posted: April 25, 2024
• Sponsor: BeiGene
• Information provided by (Responsible Party): BeiGene

Tracking Information

• First Submitted Date: October 3, 2023
• First Posted Date: October 10, 2023
• Last Update Posted Date: April 25, 2024
• Actual Study Start Date: November 11, 2023
• Estimated Primary Completion Date: February 2032 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 3, 2023)

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)

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: October 3, 2023)

• 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.
• 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.
• 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
• 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
• 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
• 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.
• 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).
• 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.
• Number of Participants with Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) [ Time Frame: Up to approximately 9 years ]
• 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).
• 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
• 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.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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
• 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.

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: CLL

Intervention

• Drug: Sonrotoclax
  Administered orally
  Other Name: BGB-11417
• Drug: Zanubrutinib
  Administered orally
  Other Name: BGB-3111
• Drug: Venetoclax
  Administered orally
• Drug: Obinutuzumab
  Administered intravenously

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)
  Interventions:

  • 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)
  Interventions:

  • Drug: Venetoclax
  • Drug: Obinutuzumab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: October 3, 2023): 640
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 2032
• Estimated Primary Completion Date: February 2032 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Study Director; 1-877-828-5568; clinicaltrials@beigene.com

• Listed Location Countries: Australia, Canada, Korea, Republic of, New Zealand, Puerto Rico, United States

Administrative Information

• NCT Number: NCT06073821
• Other Study ID Numbers: BGB-11417-301
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: BeiGene
• Original Responsible Party: Same as current
• Current Study Sponsor: BeiGene
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: BeiGene
• Verification Date: April 2024