Mosunetuzumab and Zeprumetostat in Treating Patients With Follicular Lymphoma (CUREFL03)

June 8, 2026 updated by: Institute of Hematology & Blood Diseases Hospital, China

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
80

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • China
      • Tianjin, China
        • Not yet recruiting
        • Institute of Hematology and Blood Diseases Hospital ,Chinese Academy of Medical Sciences
        • Contact:
          • Yuting Yan, Dr
    • Tianjin Municipality
      • Tianjin, Tianjin Municipality, China, 300020
        • Recruiting
        • Institute of Hematology and Blood Diseases Hospital ,Chinese Academy of Medical Sciences
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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：

    1. Histologically confirmed Grade 1-3a follicular lymphoma (FL), CD20-positive, with no evidence of histologic transformation
    2. Ann Arbor Stage III/IV
    3. No prior systemic therapy for FL
    4. Meeting at least one of the GELF criteria for indicating treatment
    5. FLIPI-1 or FLIPI-2 score of 3 to 5 (High risk)

  • Cohort 2- Previously Untreated Low-Tumor-Burden FL：

    1. Histologically confirmed Grade 1-3a, CD20-positive, Stage III/IV FL with no prior systemic therapy.
    2. Absence of B symptoms or severe pruritus
    3. Low tumor burden (LTB) not meeting GELF criteria for treatment
    4. Must have at least one measurable lesion (longest diameter >1.5 cm)
    5. Patients who are suffering from the disease or prefer active management over a watch-and-wait approach

  • Cohort 3-Relapsed or Refractory FL：

    1. Histologically confirmed Grade 1-3a, CD20-positive, Stage III/IV FL with no evidence of histologic transformation.、
    2. Relapsed or refractory disease, having received at least 1 prior systemic therapy regimen containing an anti-CD20 antibody
    3. No prior treatment with a CD20/CD3 bispecific antibody or an EZH2 inhibitor
    4. 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Cohort 1: Previously Untreated High-Risk FL
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
Other Names:
  • SHR2554
Experimental: Cohort 2: Previously Untreated Low-Tumor-Burden FL
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
Other Names:
  • SHR2554
Experimental: Cohort 3: Relapsed or Refractory FL
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
Other Names:
  • SHR2554

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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)
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
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
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.
Up to 3 years

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Objective Response Rate (ORR) (Cohorts 1, 2, and 3)
Time Frame: Up to approximately 12 months (end of treatment)
Percentage of participants achieving a Complete Response (CR) or Partial Response (PR) during the treatment period, assessed according to the Lugano 2014 classification
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
Percentage of participants experiencing disease progression within 24 months from the initiation of treatment
24 months
Progression-Free Survival (PFS)
Time Frame: Up to approximately 5 years
The time from the start of treatment to disease progression or death from any cause.
Up to approximately 5 years
Overall Survival (OS)
Time Frame: Up to approximately 5 years
The time from the start of treatment to death from any cause.
Up to approximately 5 years
Incidence and Severity of Adverse Events (AEs)
Time Frame: Up to approximately 5 years
Safety evaluated by monitoring the incidence and severity of AEs, graded according to the NCI CTCAE v5.0.
Up to approximately 5 years
Change From Baseline in EORTC QLQ-C30 Score
Time Frame: Baseline up to approximately 5 years
Evaluated using the EORTC QLQ-C30 questionnaires to assess health-related quality of life and disease-specific symptoms. Scores are transformed to a 0 to 100 scale. For global health status/quality of life and functional scales, higher scores indicate better functioning or quality of life. For symptom scales/items, higher scores indicate greater symptom burden or worse symptoms.
Baseline up to approximately 5 years
Change From Baseline in FACT-Lym LYMS Score
Time Frame: Baseline up to approximately 5 years
The Functional Assessment of Cancer Therapy-Lymphoma Lymphoma Subscale (FACT-Lym LYMS) score ranges from 0 to 60, with higher scores indicating better lymphoma-specific quality of life and fewer lymphoma-related symptoms. Evaluated using the FACT-Lym LYMS questionnaires to assess health-related quality of life and disease-specific symptoms.
Baseline up to approximately 5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Institute of Hematology & Blood Diseases Hospital, China

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 10, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 31, 2029

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 31, 2029

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 13, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 24, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 29, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 9, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 8, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • IIT2026013

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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