Mosunetuzumab and Zeprumetostat in Treating Patients With Follicular Lymphoma
A Prospective, Multicenter, Phase 2 Study of Mosunetuzumab in Combination With Zeprumetostat for the Treatment of Follicular Lymphoma
Institute of Hematology & Blood Diseases Hospital, China
80 participants
Apr 10, 2026
INTERVENTIONAL
Conditions
Summary
The purpose of this prospective, multicenter, Phase 2 study is to evaluate the efficacy and safety of Mosunetuzumab in combination with the EZH2 inhibitor Zeprumetostat (SHR2554) in patients with follicular lymphoma (FL). The study plans to enroll approximately 80 patients, who will be assigned to three distinct cohorts: previously untreated high-risk FL (Cohort 1), previously untreated low-tumor-burden FL (Cohort 2), and relapsed or refractory FL (Cohort 3). The study consists of a safety run-in phase, which will be initially conducted in Cohort 1 to assess the tolerability of the combination therapy, followed by an expansion phase across all three cohorts to further evaluate the clinical outcomes.
Eligibility
Inclusion Criteria22
- Age ≥ 18 years
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
- Adequate hematologic and organ function
- Female subjects of childbearing potential must have a negative serum pregnancy test and agree to use highly effective contraception; male subjects must agree to use effective contraception.
- Voluntary written informed consent
- Cohort 1- Previously Untreated High-Risk FL：
- Histologically confirmed Grade 1-3a follicular lymphoma (FL), CD20-positive, with no evidence of histologic transformation
- Ann Arbor Stage III/IV
- No prior systemic therapy for FL
- Meeting at least one of the GELF criteria for indicating treatment
- FLIPI-1 or FLIPI-2 score of 3 to 5 (High risk)
- Cohort 2- Previously Untreated Low-Tumor-Burden FL：
- Histologically confirmed Grade 1-3a, CD20-positive, Stage III/IV FL with no prior systemic therapy.
- Absence of B symptoms or severe pruritus
- Low tumor burden (LTB) not meeting GELF criteria for treatment
- Must have at least one measurable lesion (longest diameter >1.5 cm)
- Patients who are suffering from the disease or prefer active management over a watch-and-wait approach
- Cohort 3-Relapsed or Refractory FL：
- Histologically confirmed Grade 1-3a, CD20-positive, Stage III/IV FL with no evidence of histologic transformation.、
- Relapsed or refractory disease, having received at least 1 prior systemic therapy regimen containing an anti-CD20 antibody
- No prior treatment with a CD20/CD3 bispecific antibody or an EZH2 inhibitor
- Presence of at least one measurable or evaluable lesion at relapse
Exclusion Criteria8
- Central nervous system (CNS) lymphoma, primary mediastinal lymphoma, or evidence of histologic transformation.
- Uncontrolled cardiovascular, cerebrovascular, coagulopathy, connective tissue, or severe infectious diseases.
- Pregnant or lactating women.
- Known history of human immunodeficiency virus (HIV) or active hepatitis C virus (HCV) infection (RNA PCR positive).
- Concurrent other malignancies or history of malignancies, or anti-cancer therapy (including major surgery) within the last 4 weeks.
- Allergic reaction to the study drugs.
- Concurrent use of strong CYP3A4 inhibitors or strong CYP3A4 inducers that cannot be avoided
- Other medical or psychiatric conditions or laboratory abnormalities that, in the opinion of the investigator, may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results.
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Interventions
Mosunetuzumab is administered via intravenous (IV) infusion. It is given with step-up dosing in Cycle 1: 1 mg on Day 1, 2 mg on Day 8, and 30 mg on Day 15. From Cycle 2 onwards, 30 mg is given on Day 1. Each treatment cycle is 28 days. Treatment continues for up to 8 to 12 cycles depending on the efficacy evaluation.
Zeprumetostat is administered orally at a dose of 350 mg twice daily (BID). The treatment starts on Day 1 of Cycle 1 and continues for up to 8 or 12 cycles (each cycle is 28 days), until disease progression or unacceptable toxicity
Locations(2)
View Full Details on ClinicalTrials.gov
For the most up-to-date information, visit the official listing.
NCT07555470