Zanubrutinib (BGB-3111) in Participants With Previously Treated B-Cell Lymphoma Intolerant of Prior Bruton Tyrosine Kinase Inhibitor (BTKi) Treatment

• ClinicalTrials.gov Identifier: NCT04116437
• Recruitment Status: Recruiting
• First Posted: October 4, 2019
• Last Update Posted: April 25, 2024
• Sponsor: BeiGene
• Information provided by (Responsible Party): BeiGene

Tracking Information

• First Submitted Date: October 1, 2019
• First Posted Date: October 4, 2019
• Last Update Posted Date: April 25, 2024
• Actual Study Start Date: October 15, 2019
• Estimated Primary Completion Date: October 2025 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: May 18, 2020): Recurrence and change in severity of treatment-emergent Adverse Events (AEs) of interest. [ Time Frame: 24 months ]
• Original Primary Outcome Measures (submitted: October 2, 2019): Frequency and severity of treatment-emergent AEs of interest. [ Time Frame: 24 months ]

Current Secondary Outcome Measures (submitted: April 19, 2021)

• Overall response as determined by investigator [ Time Frame: 24 months ]
• Progression free survival (PFS) as determined by investigator [ Time Frame: 24 months ]
• Patient reported outcomes as measured by EuroQol five dimension scale (EQ-5D) [ Time Frame: 24 months ]
• Patient reported outcomes as measured by European Organisation for Research and Treatment of Cancer (EORTC) [ Time Frame: 24 months ]
• Disease control rate as determined by investigator [ Time Frame: 24 months ]

Original Secondary Outcome Measures (submitted: October 2, 2019)

• Overall response as determined by investigator. [ Time Frame: 24 months ]
• Progression free survival as determined by investigator [ Time Frame: 24 months ]
• Patient reported outcomes as measured by EQ-5D. [ Time Frame: 24 months ]
• Patient reported outcomes as measured by EORTC. [ Time Frame: 24 months ]

• Current Other Pre-specified Outcome Measures: Not Provided

Original Other Pre-specified Outcome Measures (submitted: October 2, 2019)

• Change in number of steps taken during a 6 minute walk test measured by a smart device. [ Time Frame: 24 months ]
• Change in number of daily steps taken measured by a smart device. [ Time Frame: 24 months ]
• Change in quality of life measured by a questionnaire taken on a smart device. [ Time Frame: 24 months ]

Descriptive Information

• Brief Title: Zanubrutinib (BGB-3111) in Participants With Previously Treated B-Cell Lymphoma Intolerant of Prior Bruton Tyrosine Kinase Inhibitor (BTKi) Treatment
• Official Title: A Phase 2, Multicenter, Single-arm Study of Zanubrutinib (BGB-3111) in Patients With Previously Treated B-Cell Lymphoma Intolerant of Prior Treatment With Ibrutinib and/or Acalabrutinib
• Brief Summary: The primary objective of this study is to evaluate the safety of zanubrutinib (also known as BGB-3111) in chronic lymphocytic leukemia/small lymphocytic lymphoma, Waldenström macroglobulinemia, mantle cell lymphoma, or marginal zone lymphoma patients who have become intolerant of prior ibrutinib and/or acalabrutinib treatment, by comparing intolerance to adverse event profile as assessed by the recurrence and the change in severity of adverse events.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
• Mantle Cell Lymphoma
• Marginal Zone Lymphoma
• Waldenstrom Macroglobulinemia

Intervention

Drug: Zanubrutinib

Zanubrutinib (BGB-3111) will be orally administered at a dose of 160 mg twice daily or 320mg once daily until disease progression, unacceptable toxicity, treatment consent withdrawal, or study termination.

Other Names:

• BGB-3111
• BRUKINSA

Study Arms

Experimental: Zanubrutinib

Cohort 1: Chronic lymphocytic leukemia (CLL)/ small lymphocytic lymphoma (SLL), Waldenström macroglobulinemia (WM), mantle cell lymphoma (MCL), or marginal zone lymphoma (MZL) previously treated with ibrutinib

Cohort 2: Chronic lymphocytic leukemia (CLL)/ small lymphocytic lymphoma (SLL), Waldenström macroglobulinemia (WM), mantle cell lymphoma (MCL), or marginal zone lymphoma (MZL) previously treated with acalabrutinib alone/with ibrutinib

Intervention: Drug: Zanubrutinib

• Publications *: Shadman M, Flinn IW, Levy MY, Porter RF, Burke JM, Zafar SF, Misleh J, Kingsley EC, Yimer HA, Freeman B, Rao SS, Chaudhry A, Tumula PK, Gandhi MD, Manda S, Chen DY, By K, Xu L, Liu Y, Crescenzo R, Idoine A, Zhang X, Cohen A, Huang J, Sharman JP. Zanubrutinib in patients with previously treated B-cell malignancies intolerant of previous Bruton tyrosine kinase inhibitors in the USA: a phase 2, open-label, single-arm study. Lancet Haematol. 2023 Jan;10(1):e35-e45. doi: 10.1016/S2352-3026(22)00320-9. Epub 2022 Nov 16.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: April 19, 2021): 90
• Original Estimated Enrollment (submitted: October 2, 2019): 60
• Estimated Study Completion Date: October 2025
• Estimated Primary Completion Date: October 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

Key Inclusion Criteria:

1. Participants must meet protocol defined disease criteria requiring treatment for their respective disease prior to initiation of ibrutinib or acalabrutinib

2. Ibrutinib and acalabrutinib intolerance is defined as an unacceptable toxicity where, in the opinion of the investigator, treatment should be discontinued in spite of optimal supportive care as a result of one of the following:

   1. For ibrutinib and acalabrutinib intolerance events:

      • 1 or more ≥ Grade 2 nonhematologic toxicities for >7 days (with or without treatment)
      • 1 or more ≥ Grade 3 nonhematologic toxicity of any duration
      • 1 or more Grade 3 neutropenia with infection or fever of any duration; or
      • Grade 4 heme toxicity which persists to the point that the investigator chose to stop therapy due to toxicity NOT progression.

   2. For acalabrutinib intolerance events only;

      • 1 or more ≥ Grade 1 nonhematologic toxicities of any duration with > 3 recurrent episodes; or
      • 1 or more ≥ Grade 1 nonhematologic toxicities for > 7 days (with or without treatment); or
      • Inability to use acid-reducing agents or anticoagulants (eg, proton pump inhibitors, warfarin) due to concurrent acalabrutinib use
3. Ibrutinib and/or acalabrutinib-related ≥ Grade 2 toxicities must have resolved to ≤ Grade 1 or baseline prior to initiating treatment with zanubrutinib. Grade 1 acalabrutinib-related toxicities must have resolved to Grade 0 or baseline prior to initiating treatment with zanubrutinib.
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
5. Absolute neutrophil count (ANC) ≥ 1000/mm^3 with or without growth factor support and platelet count ≥ 50,000/mm^3 (may be post-transfusion), on or prior to C1D1 of zanubrutinib

Key Exclusion Criteria:

1. Clinically significant cardiovascular disease including the following:

   1. Myocardial infarction within 6 months before the Screening
   2. Unstable angina within 3 months before the Screening
   3. New York Heart Association class III or IV congestive heart failure
   4. History of sustained ventricular tachycardia, ventricular fibrillation, and/or Torsades de Pointes
   5. QT interval corrected by Fridericia's formula > 480 milliseconds
   6. History of Mobitz II second-degree or third-degree heart block without a permanent pacemaker in place
2. History of central nervous system (CNS) hemorrhage
3. Documented progressive disease (PD) during ibrutinib and/or acalabrutinib treatment.
4. Have received any anticancer therapy (other than immunotherapy) for CLL/SLL, WM, MCL, and MZL < 7 days before any Screening assessments are performed or any immunotherapy treatment, taken alone or as part of a chemoimmunotherapy regimen, < 4 weeks before any Screening assessments are performed
5. Requires ongoing need for corticosteroid treatment > 10 mg daily of prednisone or equivalent corticosteroid. Note: Systemic corticosteroids must be fully tapered off/discontinued ≥ 5 days before the first dose of study drug is administered.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Sex/Gender

• Sexes Eligible for Study: All

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

Contacts

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

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04116437
• Other Study ID Numbers: BGB-3111-215
• 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

• Plan to Share IPD: Yes

• 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