A Phase 3 Clinical Study to Evaluate Lemzoparlimab for Injection in Combination With Azacitidine (AZA) Versus AZA Monotherapy in Treatment-naïve Patients With Higher-risk Myelodysplastic Syndrome (MDS)

Study Overview
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Brief Summary
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This phase3 study is a randomized, controlled, open-label, multicenter study to evaluate the efficacy and safety of Lemzoparlimab for injection in combination with AZA versus AZA monotherapy as first-line therapy in treatment-naïve subjects with intermediate- and high-risk MDS.

Official Title
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A Randomized, Controlled, Open-label, Multicenter Phase 3 Clinical Study to Evaluate Lemzoparlimab for Injection in Combination With Azacitidine (AZA) Versus AZA Monotherapy in Treatment-naïve Patients With Higher-risk Myelodysplastic Syndrome (MDS)

Conditions
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Myelodysplastic Syndromes(MDS)

Intervention / Treatment
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* Drug: Lemzoparlimab+Azacitidine (AZA)
* Drug: Azacitidine (AZA)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, ≥ 18 years of age at the time of signing the ICF. Subjects with intermediate- and high-risk MDS who are confirmed by bone marrow aspiration or pathological biopsy according to the diagnostic criteria of World Health Organization (WHO) 2016 or who are eligible for blasts in bone marrow and peripheral blood < 20% and have a score > 3.5 according to the revised International Prognostic Scoring System (IPSS-R). Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 2. Subjects without any prior anti-tumor therapy for MDS, including demethylated drugs (eg, AZA, decitabine), chemotherapy, targeted therapy, or HSCT. The blood transfusion or use of hematopoietic growth factors and supplementation of hematopoietic raw materials such as folic acid, vitamin B12 are permitted. For patients who ever took lenalidomide, thalidomide, antithymocyte globulin (ATG), or ciclosporin before study entry, there should be a washout period of at least 28 days prior to the first dose. Subjects who are eligible for HSCT and have no pre-scheduled HSCT at screening, or subjects who are ineligible for HSCT and have no scheduled HSCT at screening Expected survival ≥ 12 weeks Subjects with adequate organ function and laboratory tests meet the following requirements Female subjects of childbearing potential or male subjects whose partner is a woman of childbearing potential are required to use effective contraception throughout the treatment period and until 6 months after the treatment period. Subjects must be willing to provide available diagnostic evidence or undergo bone marrow aspiration and biopsy before study treatment, and must be willing to undergo bone marrow aspiration and biopsy after receiving study treatment. Subjects must give informed consent before starting the study and sign written ICF voluntarily by themselves (or their legal representatives). Subjects or their legal representatives should be able to communicate well with investigators and agree to adhere with the study protocol and complete the study Exclusion Criteria: Patients who have transformed from MDS to AML, or have been diagnosed with treatment-related MDS (t-MDS), or patients with myeloproliferative neoplasia (MPN) or myelodysplastic syndrome/myeloproliferative disorder (MDS/MPN) that meet WHO 2016 criteria Previously received any anti-CD47 antibody or SIRPα antibody or the drugs targeting the same target Subjects have received or plan to receive the allogeneic stem cell transplantation or organ transplantation during the study History of chronic hemolytic anemia due to other diseases or clinically significant positive hemolysis-related test at screening (except positive hemolysis test due to MDS) Concurrent participation in another interventional clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study Subjects plan to receive other anti-tumor therapies, including but not limited to chemotherapy, biotherapy and immunotherapy, while participating in the study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lemzoparlimab in combination with AZA<br> | Drug: Lemzoparlimab+Azacitidine (AZA)<br>* Lemzoparlimab is administered by intravenous (IV) infusion once a week at a dose of 30 mg/kg in 28-day treatment cycles Azacitidine (AZA): AZA is administered by subcutaneous injection once a day at a dose of 75 mg/m2 on D1 to D7 of each treatment cycle in 28-day treatment cycles.<br>|
| Active Comparator: AZA monotherapy<br> | Drug: Azacitidine (AZA)<br>* AZA is administered by subcutaneous injection once a day at a dose of 75 mg/m2 on D1 to D7 of each treatment cycle in 28-day treatment cycles.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival Overall Survival(OS) |  | From date of randomization until the date of first documented progression or date from any cause,whichever came first, assessed up to 50 months. |