A Prospective, Multicenter, Phase 2 Study of Mosunetuzumab in Combination With Zeprumetostat for the Treatment of Follicular Lymphoma
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.
• 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