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

NCT07550855 | Not Yet Recruiting Phase 2

• 1 other identifier: B2026-169-01
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Follicular Lymphoma (FL)

Outcome Measures

Primary Outcomes (1)

• CR rate

  Complete response rate

  Up to 6 months

Secondary Outcomes (4)

• ORR

  Up to 6 months

• DoR

  Up to 3 years

• PFS

  Up to 3 years

• OS

  Up to 3 years

Other Outcomes (1)

• Exploratory Analysis of Biomarkers and Mechanisms Related to Efficacy and Safety

  Up to 3 years

Study Arms (1)

Experimental Group

EXPERIMENTAL

Sotoclax in combination with zanubrutinib and rituximab regimen

Drug: Sotoclax in combination with zanubrutinib and rituximab regimen

Interventions

Sotoclax in combination with zanubrutinib and rituximab regimen DRUG

Zanubrutinib oral administration, Sotoclax oral administration, Rituximab intravenous injection.

Experimental Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Known active central nervous system lymphoma or leptomeningeal disease.
• Evidence of follicular lymphoma with transformation to diffuse large B-cell lymphoma.
• 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).
• History of allergy to the investigational drug, similar drugs, or excipients.
• Known history of human immunodeficiency virus (HIV) infection and/or acquired immunodeficiency syndrome (AIDS).
• Active systemic infection requiring intravenous antibiotic therapy or hospitalization (occurring within 4 weeks prior to screening).
• Confirmed progressive multifocal leukoencephalopathy (PML), positive for human T-lymphotropic virus type 1 (HTLV-1), or suspected active/latent tuberculosis.
• Pregnant or breastfeeding women, and women of childbearing potential who are unwilling to use contraception.
• Patients with significant dysfunction of vital organs.
• 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.
• 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.
• Receipt of concurrent therapy for the study disease outside of this clinical study (including the screening period).
• Autoimmune anemia and/or thrombocytopenia that does not respond adequately to corticosteroids or other standard treatments.
• Receipt of medications known to prolong the QT/QTc interval.
• Vaccination with a live vaccine within ≤35 days prior to the first dose of study drug.

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (1)

Sun Yat-sen Universitiy Cancer Center

Guangzhou, Guangdong, China

Location

MeSH Terms

Conditions

Lymphoma, Follicular

Interventions

zanubrutinib

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Qingqing Cai

  Sun Yat-sen Universitiy Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Qingqing Cai

CONTACT

(020)87342823; caiqq@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: April 19, 2026
• First Posted: April 24, 2026
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): March 30, 2028
• Study Completion (Estimated): September 30, 2029
• Last Updated: April 24, 2026

Record last verified: 2026-04

Locations

CN (1)