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.
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.
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).
Parallel
Mosunetuzumab
DrugMosunetuzumab 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
DrugZeprumetostat 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
Best Complete Response (CR) Rate (Cohort 1 and Cohort 3)
The best complete response (CR) rate is defined as the percentage of participants who achieve a complete response during the treatment period, as assessed by the investigator according to the Lugano 2014 classification criteria
3-Year Event-Free Survival (EFS) Rate (Cohort 2)
Event-Free Survival (EFS) is defined as the time from the start of treatment to the first occurrence of any of the following events: progression to high-tumor-burden (HTB) based on GELF criteria, initiation of cytotoxic chemotherapy and/or radiotherapy, histologic transformation, or death from any cause.
Objective Response Rate (ORR) (Cohorts 1, 2, and 3)
Percentage of participants achieving a Complete Response (CR) or Partial Response (PR) during the treatment period, assessed according to the Lugano 2014 classification
Rate of Progression of Disease within 24 Months (POD24) (Cohorts 1, 2, and 3)
Percentage of participants experiencing disease progression within 24 months from the initiation of treatment
Progression-Free Survival (PFS)
The time from the start of treatment to disease progression or death from any cause.
Overall Survival (OS)
The time from the start of treatment to death from any cause.
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