Sonrotoclax, Zanubrutinib and Rituximab in Previously Untreated Patients With Follicular Lymphoma (FLOURISH)

A Phase II, Multicenter, Single-Arm Study of Sonrotoclax, Zanubrutinib and Rituximab in Previously Untreated Patients With Follicular Lymphoma (FLOURISH)

Follicular lymphoma (FL) remains an incurable indolent B-cell lymphoma for many patients, and although rituximab-based chemoimmunotherapy can achieve high initial response rates, a substantial proportion of patients experience early progression, including POD24, which is associated with poor long-term outcomes. This underscores the need for more effective and better-tolerated frontline treatment strategies, particularly chemotherapy-free approaches. The present study is based on a strong biologic rationale that simultaneously targets two key pathogenic mechanisms in FL: aberrant B-cell receptor signaling and impaired apoptosis driven by BCL2 overexpression. Zanubrutinib, a next-generation BTK inhibitor, has shown clinical activity with a favorable safety profile in FL, while sonrotoclax, a potent and highly selective next-generation BCL2 inhibitor, has demonstrated promising preclinical and early clinical activity. In combination with rituximab, this chemotherapy-free triplet regimen may produce deeper and more durable remissions while maintaining manageable toxicity, and therefore has the potential to expand frontline treatment options and improve outcomes for patients with previously untreated FL.

Study Overview

• Status: Not yet recruiting
• Conditions: Follicular Lymphoma (FL)
• Intervention / Treatment: Drug: Sotoclax in combination with zanubrutinib and rituximab regimen

• Study Type: Interventional
• Enrollment (Estimated): 52
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Qingqing Cai; Phone Number: (020)87342823; Email: caiqq@sysucc.org.cn

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China
      • Sun Yat-sen Universitiy Cancer Center
      • Contact: Qingqing Cai; Phone Number: (020)87342823; Email: caiqq@sysucc.org.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Willing to participate in the clinical study and signed informed consent.
2. Age ≥18 years, no gender restrictions.
3. Pathologically diagnosed with follicular lymphoma (Grade 1, 2, or 3a) and previously untreated.
4. Has at least one measurable or assessable lesion.
5. Ann-Arbor stage III or IV, or stage II with bulky disease.
6. Meets at least one GELF criterion.
7. Eastern Cooperative Oncology Group (ECOG) performance status score ≤2.
8. Adequate major organ function.

Exclusion Criteria:

1. Known active central nervous system lymphoma or leptomeningeal disease.
2. Evidence of follicular lymphoma with transformation to diffuse large B-cell lymphoma.
3. Prior history of other malignancies other than follicular lymphoma (except for those with disease-free survival ≥5 years and assessed by the investigator as having low risk of recurrence).
4. History of allergy to the investigational drug, similar drugs, or excipients.
5. Known history of human immunodeficiency virus (HIV) infection and/or acquired immunodeficiency syndrome (AIDS).
6. Active systemic infection requiring intravenous antibiotic therapy or hospitalization (occurring within 4 weeks prior to screening).
7. Confirmed progressive multifocal leukoencephalopathy (PML), positive for human T-lymphotropic virus type 1 (HTLV-1), or suspected active/latent tuberculosis.
8. Pregnant or breastfeeding women, and women of childbearing potential who are unwilling to use contraception.
9. Patients with significant dysfunction of vital organs.
10. Receipt of any moderate or strong CYP3A4 inhibitors or strong CYP3A4 inducers within 14 days (or 5 half-lives, whichever is longer) prior to the first dose of sotoclax.
11. Use of strong cytochrome P450 (CYP) 3A4 inhibitors within 7 days prior to the first dose of zanubrutinib, or requirement for continuous use of strong CYP3A inhibitors/inducers.
12. Receipt of concurrent therapy for the study disease outside of this clinical study (including the screening period).
13. Autoimmune anemia and/or thrombocytopenia that does not respond adequately to corticosteroids or other standard treatments.
14. Receipt of medications known to prolong the QT/QTc interval.
15. Vaccination with a live vaccine within ≤35 days prior to the first dose of study drug.
16. Major surgery within 4 weeks prior to the first dose of study drug.
17. Unwillingness or inability to complete all assessments and procedures required by the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental Group; Sotoclax in combination with zanubrutinib and rituximab regimen	Drug: Sotoclax in combination with zanubrutinib and rituximab regimen; Zanubrutinib oral administration, Sotoclax oral administration, Rituximab intravenous injection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CR rate	Complete response rate	Up to 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
OS	Overall survival	Up to 3 years
ORR	Overall response rate	Up to 6 months
DoR	Duration of response	Up to 3 years
PFS	Progression free survival	Up to 3 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exploratory Analysis of Biomarkers and Mechanisms Related to Efficacy and Safety	Tumor tissue and peripheral blood samples will be analyzed using multi-omics approaches to explore biomarkers and biological mechanisms associated with efficacy and safety.	Up to 3 years

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Investigators: Principal Investigator: Qingqing Cai, Sun Yat-sen Universitiy Cancer Center

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): March 30, 2028
• Study Completion (Estimated): September 30, 2029

Study Registration Dates

• First Submitted: April 19, 2026
• First Submitted That Met QC Criteria: April 19, 2026
• First Posted (Actual): April 24, 2026

Study Record Updates

• Last Update Posted (Actual): April 24, 2026
• Last Update Submitted That Met QC Criteria: April 19, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Hemic and Lymphatic Diseases; Lymphoma, Follicular; zanubrutinib
• Other Study ID Numbers: B2026-169-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No