Title
A Phase 3 Randomized Double-Blind Multicenter Study of Sonrotoclax Plus Zanubrutinib Versus Placebo Plus Zanubrutinib in Patients With Relapsed/Refractory Mantle Cell Lymphoma

Description
A Phase 3 Randomized Double-Blind Multicenter Study of Sonrotoclax Plus Zanubrutinib Versus Placebo Plus Zanubrutinib in Patients With Relapsed/Refractory Mantle Cell Lymphoma

Objective
Primary Objective:
- To demonstrate superiority of sonrotoclax plus zanubrutinib over placebo plus zanubrutinib as measured by progression-free survival (PFS) determined by a blinded independent review committee (BIRC).

Key Secondary Objective:
- To compare the efficacy of sonrotoclax plus zanubrutinib with that of placebo plus zanubrutinib as measured by overall survival (OS).

Other Secondary Objectives:
- To evaluate efficacy, as measured by the following:
-- PFS determined by investigator.
-- Overall response rate (ORR), as determined by BIRC and by investigator assessment (INV), per Lugano 2014 criteria.
-- Complete response rate (CRR), as determined by BIRC and by investigator.
-- Duration of response (DOR), as determined by BIRC and by investigator.
-- Time to first response, as determined by BIRC and by investigator.
-To evaluate patient-reported disease and treatment symptoms.
-To evaluate safety and tolerability.

Treatment The goal of this study is to compare how well sonrotoclax plus zanubrutinib works versus zanubrutinib plus placebo in treating adults with relapsed/refractory (R/R) mantle cell lymphoma (MCL). This study will also look at the safety of sonrotoclax plus zanubrutinib versus zanubrutinib plus placebo.

Key Eligibility Inclusion Criteria:

-Histologically locally confirmed diagnosis of MCL based on the World Health Organization 2022 classification of Haematolymphoid Tumors (WHO-HAEM5), or based on International Consensus Classification (ICC)
-Ability to provide archival or fresh tumor tissue for retrospective central confirmation of MCL diagnosis
-Received 1 to 5 prior lines of systemic therapy including an anti-CD20 monoclonal antibody (mAb)-based immunotherapy or chemoimmunotherapy and requiring treatment in the opinion of the investigator
-Relapsed or refractory disease after the last line of therapy
-Measurable disease defined as >/= 1 nodal lesion that is > 1.5 cm in longest diameter, or >/= 1 extranodal lesion that is > 1 cm in longest diameter
-Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2
-Adequate organ function

Applicable Disease Sites
Lymphoma

Participating Institutions
UW Health Eastpark Medical Center; UW Health University Hospital