Mosunetuzumab and Zeprumetostat in Treating Patients With Follicular Lymphoma

Official title

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

Overview

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.

Detailed description

This is a prospective, open-label, multicenter, multi-cohort phase 2 study evaluating Mosunetuzumab combined with Zeprumetostat (SHR2554) in follicular lymphoma (FL). The study is conducted in two stages:

Stage 1: Safety Run-in Phase Initially, 6 participants in Cohort 1 will be enrolled to evaluate dose-limiting toxicities (DLTs) during Cycle 1 (28 days). If the safety is acceptable, the study will proceed to Stage 2.

Stage 2: Expansion Phase

Enrollment will expand to three independent cohorts:

Cohort 1: Previously untreated high-risk FL (FLIPI 3-5). Cohort 2: Previously untreated low-tumor-burden FL. Cohort 3: Relapsed or refractory FL.

Interventions

• Drug Mosunetuzumab
  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.
• Drug Zeprumetostat
  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

Primary outcome measures

• Best Complete Response (CR) Rate (Cohort 1 and Cohort 3) [Time frame: Up to approximately 12 months (From start of treatment until the end of up to 12 cycles of treatment)]
• 3-Year Event-Free Survival (EFS) Rate (Cohort 2) [Time frame: Up to 3 years]

Secondary outcome measures (7)

• Objective Response Rate (ORR) (Cohorts 1, 2, and 3) [Time frame: Up to approximately 12 months (end of treatment)]
• Rate of Progression of Disease within 24 Months (POD24) (Cohorts 1, 2, and 3) [Time frame: 24 months]
• Progression-Free Survival (PFS) [Time frame: Up to approximately 5 years]
• Overall Survival (OS) [Time frame: Up to approximately 5 years]
• Change From Baseline in EORTC QLQ-C30 Score [Time frame: Baseline up to approximately 5 years]
• Change From Baseline in FACT-Lym LYMS Score [Time frame: Baseline up to approximately 5 years]
• Incidence and Severity of Adverse Events (AEs) [Time frame: Up to approximately 5 years]

Eligibility criteria

Inclusion criteria

• 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 criteria

• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 2 centers

• Institute of Hematology and Blood Diseases Hospital ,Chinese Academy of Medical Sciences — Tianjin
• Institute of Hematology and Blood Diseases Hospital ,Chinese Academy of Medical Sciences — Tianjin

Identifiers

NCT: NCT07555470 · IIT2026013

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗