A Phase 1, Multicenter, Open-Label, Dose-Escalation and Expansion, Safety, Pharmacokinetic, Pharmacodynamic, and Clinical Activity Study of Intravenously Administered IO-202 and IO-202 + Azacitidine ± Venetoclax in Acute Myeloid Leukemia (AML) Patients With Monocytic Differentiation and in Chronic Myelomonocytic Leukemia (CMML) Patients
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 67
- 试验地点
- 14
- 主要终点
- Safety of IO-202 and IO-202 plus azacitidine ± venetoclax as measured by incidence of adverse events.
研究概览
简要总结
To assess safety and tolerability at increasing dose levels of IO-202 in successive cohorts of participants with AML with monocytic differentiation and CMML in order to estimate the maximum tolerated dose (MTD) or maximum administered dose (MAD) and select the recommended Phase 2 dose (RP2D)
详细描述
This is a Phase 1, Multicenter, Open-Label, Dose-Escalation and Expansion, Safety, Pharmacokinetic, Pharmacodynamic, and Clinical Activity Study of Intravenously Administered IO-202 and IO-202 + Azacitidine ± Venetoclax in Acute Myeloid Leukemia (AML) Patients with Monocytic Differentiation and in Chronic Myelomonocytic Leukemia (CMML) Patients
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients must be ≥
- •For the Part 1 Dose-Escalation Phase, patients must be diagnosed with the following:
- •Relapsed or refractory AML with myelomonocytic or monoblastic/monocytic differentiation according to the World Health Organization 2016 criteria and has failed treatment with available therapies known to be active for AML.
- •Relapsed or refractory CMML and has failed treatment with available therapies known to be active for CMML
- •Part 2 Expansion Phase:
- •Relapsed or refractory LILRB4high AML with myelomonocytic or monoblastic/monocytic differentiation and has failed treatment with available therapies known to be active for AML.
- •Hypomethylating-agent naive CMML regardless of LILRB4 expression levels.
- •Newly diagnosed high LILRB4 expression monocytic AML patients considered to be ineligible for standard induction therapy.
- •Patients must be amenable to serial BM aspirates/biopsies and peripheral blood sampling during the study.
- •Patients must be able to understand and willing to sign an informed consent. A legally authorized representative may consent.
- •Patients must have an ECOG performance status of 0 to 2
- •Patients must have adequate hepatic function
- •Patients must have adequate renal function
- •Patients must be recovered from any clinically relevant toxic effects of any prior surgery, radiotherapy, or other therapy intended for the treatment of cancer.
- •Patients must be off systemic calcineurin inhibitors for at least 4 weeks prior to study drug treatment.
- •Female patients with reproductive potential must have a negative serum pregnancy test within 7 days prior to the start of therapy.
排除标准
- •Patients who have previously received a monoclonal antibody therapy targeting LILRB
- •Patients who have undergone HSCT within 60 days of the first dose of IO-
- •Patients who received systemic anti-cancer therapy or radiotherapy <7 days prior to their first day of study drug administration (Hydroxyurea or leukapheresis is allowed up to 24 hours prior to the first dose.
- •Patients who received an investigational agent <7 days prior to their first day of study drug administration.
- •Patients for whom potentially curative anti-cancer therapy is available.
- •Patients who are pregnant or breastfeeding.
- •Patients with uncontrolled, active infection.
- •Patients with known hypersensitivity to any of the components of the IO-202 formulation.
- •Patients with known pulmonary lesions and/or history of pneumonitis or interstitial lung disease.
- •Active known malignancy.
- •Patients with New York Heart Association (NYHA) Class III or IV congestive heart failure (CHF) or left ventricular ejection fraction (LVEF) <40%.
- •Ongoing cardiac dysrhythmias Grade 2 or higher per of NCI CTCAE, Version 5.0, Grade ≥
- •Known or suspected hypersensitivity to recombinant proteins.
- •Known active bacterial, viral, and/or fungal infection.
- •Patients with any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol.
- •Patients with clinical signs and/or symptoms suggesting active, uncontrolled central nervous system (CNS) leukemia or known active, uncontrolled CNS leukemia.
- •Patients with immediately life-threatening, severe complications of leukemia.
- •Donor Lymphocyte Infusion within 30 days prior to first IO-202 administration.
- •Current active treatment in another interventional therapeutic clinical study.
- •Chronic systemic corticosteroid treatment with a dose of >10 mg prednisone/day or dose equivalent.
- •Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the patient inappropriate for entry into this study.
- •Acute Promyelocytic Leukemia patients or patients with known Philadelphia chromosome (Ph+) positive AML or chronic myelogenous leukemia (CML) blast crisis.
- •Hyperleukocytosis (leukocytes ≥25 x 10e9/L) at first dose of IO-202.
研究组 & 干预措施
Dose Escalation of IO-202
Dose cohorts treated with intravenous (IV) IO-202 monotherapy in ascending doses.
干预措施: IO-202 (Biological)
Dose Escalation of IO-202 Plus Azacitidine
AZA Dose cohorts treated with intravenous (IV) IO-202 in ascending doses plus Azacitidine (IV or SC) on days 1-7 of each 28-day cycle.
干预措施: IO-202 and Azacitidine (Biological)
Dose Expansion of IO-202 plus Azacitidine AML
To enroll high LILRB4 expression monocytic AML patients refractory to or relapsed after available therapies known to be active in AML.
干预措施: IO-202 and Azacitidine (Biological)
Dose Expansion of IO-202 plus Azacitidine CMML
To enroll hypomethylating-agent naive CMML patients.
干预措施: IO-202 and Azacitidine (Biological)
Dose Expansion of IO-202 plus Azacitidine + Venetoclax (Ven)
To enroll newly diagnosed high LILRB4 expression AML patients who are unfit for intensive induction chemotherapy.
干预措施: IO-202 and Azacitidine + Venetoclax (Biological)
结局指标
主要结局
Safety of IO-202 and IO-202 plus azacitidine ± venetoclax as measured by incidence of adverse events.
时间窗: From first dose of IO-202 to 30 days following last study treatment
Severity of adverse events
Tolerability of IO-202 and IO-202 plus azacitidine ± venetoclax as measured by incidence and duration of dose interruptions and dose reductions of study treatment.
时间窗: From first dose of IO-202 to 30 days following last study treatment
Incidence dose interruptions and dose reductions
次要结局
- To evaluate the incidence of anti-drug antibodies against IO-202(Through study completion, an average of 1 year)
- To characterize the pharmacokinetics (PK) of IO-202 and IO-202 plus azacitidine ± venetoclax and as defined by maximum plasma concentration (Cmax)(Through study completion, an average of 1 year)
- To measure rates of response to IO-202 and IO-202 plus azacitidine ± venetoclax(Through study completion, an average of 1 year)
- To characterize the PK of IO-202 and IO-202 IO-202 plus azacitidine ± venetoclax as defined by area under the curve (AUC)(Through study completion, an average of 1 year)