A Study to Investigate Efficacy and Safety of BCL2 Inhibitor Sonrotoclax as Monotherapy and in Combination With Zanubrutinib in Adults With Waldenström Macroglobulinemia

BeiGene

Status and phase: Enrolling; Phase 2

Conditions: Waldenstrom's Macroglobulinemia Refractory; Waldenstrom Macroglobulinemia; Waldenstrom's Macroglobulinemia Recurrent

Treatments: Drug: Sonrotoclax; Drug: Zanubrutinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT05952037

2023-503235-18-00 (EU Trial (CTIS) Number)

CTR20232718 (Registry Identifier)

BGB-11417-203

U1111-1291-4524 (Registry Identifier)

Details and patient eligibility

About

This study will evaluate the safety and efficacy of the BCL2 inhibitor sonrotoclax (BGB-11417) in participants with relapsed/refractory Waldenström's Macroglobulinemia (R/R WM) and in combination with zanubrutinib in adult participants with previously untreated WM.

Full description

This study will test whether sonrotoclax (BGB-11417) can be used to improve outcomes in participants with Waldenström's Macroglobulinemia (WM) both when used alone in those who have not responded well to conventional treatments and when used in combination with zanubrutinib in those who have not yet received treatment. The main goals of the study are to determine how many participants 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 105 participants. All participants will receive sonrotoclax 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.

Enrollment: 105 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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).
• For Cohorts 1-3, refractory or relapsed disease 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.
• For Cohort 4, patients must not have received prior therapy for WM (except for plasmapheresis).
• 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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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105 participants in 4 patient groups

Cohort 1

Experimental group

Description:

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 sonrotoclax at a standard dose, given orally once daily.

Treatment:

Drug: Sonrotoclax

Cohort 2

Experimental group

Description:

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 sonrotoclax at a standard dose, given orally once daily.

Treatment:

Drug: Sonrotoclax

Cohort 3

Experimental group

Description:

Participants with R/R disease to a BTK inhibitor treatment and are unsuitable for chemoimmunotherapy will receive sonrotoclax at a standard dose, given orally once daily.

Treatment:

Drug: Sonrotoclax

Cohort 4

Experimental group

Description:

Participants with previously untreated WM will receive sonrotoclax and zanubrutinib combination therapy for a fixed duration.

Treatment:

Drug: Zanubrutinib

Drug: Sonrotoclax