A Clinical Study of 6MW3211 Monotherapy or Combination Therapy for AML or MDS

Study Overview
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Brief Summary
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This study is aimed to evaluate the efficacy, safety, immunogenicity and pharmkinetics, pharmacodynamics of 6MW3211 as monotherapy and in combination with AZA or AZA plus VEN in patients with AML/MDS.

Detailed Description
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This study is a phase I/II study to evaluate the pharmacokinetics, pharmacodynamics, efficacy and safety of 6MW3211 monotherapy or combined with AZA or AZA plus VEN in patients with AML and MDS. There will be 2 parts of this study. The phase Ib is about monotherapy of 6MW3211 and Phase II is designed to evaluate the safety and efficacy of 6MW3211 combined with AZA or AZA plus VEN in patients with relapse/refractory and newly diagnosed AML and MDS.

Official Title
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A Study to Evaluate Pharmcokinetics, Pharmacodynamics , Efficacy and Safety of 6MW3211 Monotherapy and in Combination With Azacitidine(AZA) or AZA Plus Venetoclax(VEN) in Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS)

Conditions
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Acute Myeloid Leukemia, Myelodysplastic Syndrome

Intervention / Treatment
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* Drug: 6MW3211 injection with Intravenous Infusion


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Voluntarily participate in the study and sign the informed consent; 18≤age≤75，Men or women； AML patients (except acute promyelocytic leukemia) : subjects who meet the diagnostic criteria for relapsed/refractory AML according to the diagnostic criteria of 2021 Chinese Guidelines for the Diagnosis and Treatment of Relapsed and Refractory AML ； MDS patients: MDS patients were diagnosed as having moderate risk of recurrence/refractory (IPSS-R score >3.5) according to WHO diagnostic criteria in 2016 ECOG:0-2; Survival expectation of at least 3 months; Adequate organs and hematopoietic functions; only applicable for phase II : Newly diagnosed AML with intolerance to standard induction chemotherapy who should meet one of following criterias: age ≥75 years; ECOG 2-3; chronic heart failure requiring treatment or EF≤50% or chronic stable angina pectoris; DLCO≤65% or FEV1≤65%;30ml/min≤CrCl<45ml/min；1.5 x ULN<total bilirubin≤3.0 x ULN Newly diagnosed intermediate- and high-risk (International Prognostic Scoring System IPSS-R) MDS Exclusion criteria: Myeloid proliferative diseases (MPN), including primary myelofibrosis (PMF), polycythemia vera (PV), chronic myelogenous leukemia (CML), and primary thrombocytopenia (ET); Or have myelodysplastic myeloid proliferative tumors (MDS-MPN), including chronic monocytic leukemia (CMML), atypical chronic myelogenous leukemia (aCML), juvenile granulomatous single-cell leukemia (JMML), and acute promyelocytic leukemia (M3); Recurrence after allogeneic hematopoietic stem cell transplantation, or autologous hematopoietic stem cell transplantation within 1 year; Known infiltration of central nervous system leukemia； Active or uncontrolled autoimmune diseases； Has a history of other malignancies； Has known inherited or acquired hemorrhagic disorders； Pregnant or lactating women；

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 6MW3211<br>Phase I, 6MW3811 monotherapy in 2 dose levels of 30mg/kg or 45mg/kg; phase II, 6MW3811 will be given in combination with AZA( cohort1) and AZA plus VEN(cohort 2) | Drug: 6MW3211 injection with Intravenous Infusion<br>* phaseI: 6MW3211 will be administered in 30mg/kg and 45mg/kg intravenously once every 2 weeks; phaseII: 6MW3211 will be administered in 45mg/kg intravenously in both 2 cohorts.AZA will be administered in 75mg/m2 by subcoutaneous injection in cohort 1 as well as cohort 2 from Day1-Day7 every 28-day cycle. VEN will be administered orally with dose escalation to 400mg daily every cycle.<br>* Other names: infusion;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CCR | Compound complete response rate | 1 year | 
| ORR | Objective Response Rate | 1 year | 
| phase II: safety | to evaluate the percentage of participants with adverse events and serious adverse events of 6MW3211 combination therapy in AML and MDS | Up to 28 days post last dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AE | All the adverse events | Up to 28 days post last dose | 
| DoCR | Duration of complete response | 1 year | 
| RFS | Relapse-free survival | 1 year | 
| EFS | Event-free survival | 1 year | 
| OS | Overall survival | 1 year | 
| PK Parameter | The area under the curve (AUC) | 1 year | 
| Cmax | Maximum concentration | 1 year | 
| Tmax | Time at which maximum concentration | 1 year | 
| T1/2 | The half life | 1 year |