Follicular Lymphoma
Conditions
Brief 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.
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
DRUGMosunetuzumab
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.
DRUGZeprumetostat
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
Sponsors
Institute of Hematology & Blood Diseases Hospital, China
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Best Complete Response (CR) Rate (Cohort 1 and Cohort 3) | 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 |
| 3-Year Event-Free Survival (EFS) Rate (Cohort 2) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) (Cohorts 1, 2, and 3) | 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 |
| Rate of Progression of Disease within 24 Months (POD24) (Cohorts 1, 2, and 3) | 24 months | Percentage of participants experiencing disease progression within 24 months from the initiation of treatment |
| Progression-Free Survival (PFS) | Up to approximately 5 years | The time from the start of treatment to disease progression or death from any cause. |
| Overall Survival (OS) | Up to approximately 5 years | The time from the start of treatment to death from any cause. |
| Change From Baseline in EORTC QLQ-C30 Score | 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. |
| Change From Baseline in FACT-Lym LYMS Score | 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. |
| Incidence and Severity of Adverse Events (AEs) | Up to approximately 5 years | Safety evaluated by monitoring the incidence and severity of AEs, graded according to the NCI CTCAE v5.0. |
Countries
China
Contacts
CONTACTShuhua Yi, Dr
Outcome results
None listed