Study to Evaluate the Efficacy and Safety of BGB-11417 in Participants With Waldenström's Macroglobulinemia

Study Overview
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Brief Summary
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This study will evaluate the safety and efficacy of the BCL2 inhibitor BGB-11417 in participants with relapsed/refractory Waldenström's Macroglobulinemia (R/R WM) in 3 cohorts.

Detailed Description
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This study will test whether BGB-11417 can be used to improve outcomes in participants with Waldenström's Macroglobulinemia (WM) who have not responded well to conventional treatments. The main goals of the study are to determine how many participants may no longer have evidence of cancer or have some improvement in the signs and symptoms of cancer after treatment, and to determine what adverse events, or side effects, participants might experience. BCL2 is a key protein involved in cell death, and abnormal levels of BCL2 are associated with many cancers. Blocking the action of BCL2 proteins is a promising approach with potential therapeutic benefits in participants with different types of cancers, including WM. This study will enroll approximately 85 patients. All patients will receive BGB-11417 orally as a tablet. The study will take place at multiple centers worldwide. The overall time to participate in this study is approximately 5 years. Treatments will continue until participants experience worsening disease status, too many side effects, or withdraw consent.

Official Title
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An Open-Label, Multicenter Phase 2 Study to Evaluate the Efficacy and Safety of BCL2 Inhibitor BGB-11417 in Patients With Relapsed/Refractory Waldenström's Macroglobulinemia

Conditions
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Waldenstrom Macroglobulinemia, Waldenstrom's Macroglobulinemia Recurrent, Waldenstrom's Macroglobulinemia Refractory

Intervention / Treatment
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* Drug: BGB-11417


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical and definitive histologic diagnosis of WM. Meeting ≥ 1 criterion for treatment according to consensus panel criteria from the 2nd International Workshop on Waldenström's Macroglobulinemia (IWWM). Refractory or relapsed disease to the most recent therapy at study entry unless participants had intolerance to the most recent therapy. Refractory disease is defined as not attaining at least a major response, or progressing while on or within 6 months of completing therapy. Relapsed disease is defined as attaining at least a major response to therapy and meeting the criteria for disease progression beyond 6 months after completing therapy. Adequate organ function. Exclusion Criteria: Central nervous system (CNS) involvement by WM. Transformation to aggressive lymphoma, such as diffuse large B-cell lymphoma. History of other malignancies ≤ 2 years before study entry. Uncontrolled active systemic infection or recent infection requiring parenteral antimicrobial therapy that was completed ≤ 14 days before the first dose of the study drug. Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>Participants with R/R disease to both Bruton tyrosine kinase (BTK) inhibitor and anti-CD20 antibody-based systemic therapy containing chemotherapy or proteasome inhibitor will receive BGB-11417 at a standard dose, given orally once daily. | Drug: BGB-11417<br>* Administered orally as a tablet.<br>* Other names: Sonrotoclax;|
| Experimental: Cohort 2<br>Participants with R/R disease to anti-CD20 antibody-based systemic therapy containing chemotherapy or proteasome inhibitor and were intolerant to BTK inhibitor will receive BGB-11417 at a standard dose, given orally once daily. | Drug: BGB-11417<br>* Administered orally as a tablet.<br>* Other names: Sonrotoclax;|
| Experimental: Cohort 3<br>Participants with R/R disease to a BTK inhibitor treatment and are unsuitable for chemoimmunotherapy will receive BGB-11417 at a standard dose, given orally once daily. | Drug: BGB-11417<br>* Administered orally as a tablet.<br>* Other names: Sonrotoclax;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Major Response Rate (MRR) in Cohort 1 | MRR is defined as the percentage of participants who achieved complete response (CR), very good partial response (VGPR), or partial response (PR), as assessed by the Independent Review Committee (IRC). | Up to approximately 4 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MRR in Cohorts 1, 2, and 3 | MRR is defined as the percentage of participants who achieved complete response (CR), very good partial response (VGPR), or partial response (PR), as assessed by the investigator (Cohorts 1, 2, and 3) and by the IRC (Cohorts 2 and 3). | Up to approximately 5 years | 
| Duration of Response (DOR) | DOR is defined as the time from the date that response criteria are first met to the date that progressive disease is objectively documented or death, whichever comes first, as assessed by the IRC and by the investigator. | Up to approximately 5 years | 
| CR + VGPR rate | CR + VGPR is defined as the percentage of participants who achieve CR or VGPR, as assessed by the IRC and by the investigator. | Up to approximately 5 years | 
| Overall Response Rate (ORR) | ORR is defined as the percentage of participants with minor response (MR) or better, as assessed by the IRC and by the investigator. | Up to approximately 5 years | 
| Progression-Free Survival (PFS) | PFS is defined as the time from first dose until first documentation of progression or death, whichever comes first, as assessed by the IRC and by the investigator. | Up to approximately 5 years | 
| Time to major response | Time to major response is defined as the time from start of study treatment to the first documentation of major response, as assessed by the IRC and by the investigator. | Up to approximately 5 years | 
| Overall Survival (OS) | OS is defined as the time from first study drug administration to the date of death due to any cause. | Up to approximately 5 years | 
| Number of participants reporting adverse events | Number of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs), including laboratory abnormalities, physical examination results, and vital signs. | Up to approximately 5 years | 
| Health-Related Quality of Life (HRQoL): NFLymSI-18 | HRQoL based on participant-reported outcomes using National Comprehensive Cancer Network/Functional Assessment of Cancer Therapy Lymphoma Cancer Symptom Index - 18 Item (NFLymSI-18) Version 4. The questionnaire contains 18 items, each of which utilizes a Likert scale with 5 possible responses ranging from 0 'Not at all' to 4 'Very much' and is divided into a total score. | Up to approximately 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Waldenström's macroglobulinemia, Waldenstrom's Macroglobulinemia Recurrent, Waldenstrom's Macroglobulinemia Refractory, Lymphoma