A Phase 1b/2 Study of AK117 (Anti-CD47 Antibody) in Combination With Azactidine Plus Venetoclax in Patients With Acute Myeloid Leukemia
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 180
- 试验地点
- 1
- 主要终点
- Phase 1b/2: Number of participants with adverse events (AEs)
研究概览
简要总结
This is a phase 1b/2 study. All patients are diagnosed with Acute Myeloid Leukemia (AML), Eastern Cooperative Oncology Group (ECOG) performance status 0-3. The purpose of this study is to evaluate the safety and efficacy of AK117 + azacitidine + venetoclax in subjects with AML.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Age ≥ 18 years old at the time of enrolment.
- •Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0~3, and 0~2 are required for subjects ≥75 years old.
- •Has a life expectancy of at least 12 weeks.
- •Diagnosed as AML diagnosed according to WHO 2022 criteria.
- •Has adequate organ function.
- •All female and male subjects of reproductive potential must agree to use an effective method of contraception, as determined by the Investigator, during and for 120 days after the last dose of study treatment.
排除标准
- •Diagnosed with acute promyelocytic leukemia, BCR-ABL1-positive AML, myeloid sarcoma, mixed phenotype acute leukemia (MPAL), accelerated phase or blast crisis of Chronic Myeloid Leukemia.
- •has central nervous system leukemia (CNSL).
- •Favorable risk cytogenetics such as t(8;21), inv(16) or t(16;16) or t(15;17) as per the National Comprehensive Cancer Network (NCCN) Guidelines Version 6, 2023 for AML.
- •Previously diagnosed with another malignancy or have any evidence of residual disease.
- •Previous allogeneic hematopoietic stem cell transplant (allo-HSCT).
- •Prior treatment with any B-cell lymphoma 2 (Bcl-2) inhibitors, anti-CD47 or anti-SIRPα (signal regulatory protein alpha) agent.
- •Use strong or moderate cytochrome P450 (CYP) 3A inducers systemically within one week prior to enrollment, or currently require long-term treatment with a moderate to strong CYP3A inducer.
- •Previously diagnosed with MDS and treated with demethylating drugs.
- •Patients with known cardiopulmonary disease defined as unstable angina, clinically significant arrhythmia, congestive heart failure (New York Heart Association Class III or IV), decompensated cirrhosis, nephrotic syndrome, uncontrolled metabolic disorders.
- •Other conditions where the investigator considers the patient inappropriate for enrollment.
研究组 & 干预措施
AK117+Azacitidine+Venetoclax
Phase Ib: Subjects will receive: A117: different doses on every 2 weeks, azacitidine: 75 mg/m^2 on Days 1-7 each cycle, venetoclax: 100 mg on Cycle 1 Day 1, 200 mg on Cycle 1 Day 2, 400 mg on Cycle 1 Day 3 and daily thereafter;
Phase II: Subjects will receive: AK117: the recommended Phase 2 dose (RP2D) on every two weeks, azacitidine: 75 mg/m^2 on Days 1-7 each cycle, venetoclax: 100 mg on Cycle 1 Day 1, 200 mg on Cycle 1 Day 2, 400 mg on Cycle 1 Day 3 and daily thereafter.
干预措施: AK117 (Drug)
AK117+Azacitidine+Venetoclax
Phase Ib: Subjects will receive: A117: different doses on every 2 weeks, azacitidine: 75 mg/m^2 on Days 1-7 each cycle, venetoclax: 100 mg on Cycle 1 Day 1, 200 mg on Cycle 1 Day 2, 400 mg on Cycle 1 Day 3 and daily thereafter;
Phase II: Subjects will receive: AK117: the recommended Phase 2 dose (RP2D) on every two weeks, azacitidine: 75 mg/m^2 on Days 1-7 each cycle, venetoclax: 100 mg on Cycle 1 Day 1, 200 mg on Cycle 1 Day 2, 400 mg on Cycle 1 Day 3 and daily thereafter.
干预措施: Azacitidine (Drug)
AK117+Azacitidine+Venetoclax
Phase Ib: Subjects will receive: A117: different doses on every 2 weeks, azacitidine: 75 mg/m^2 on Days 1-7 each cycle, venetoclax: 100 mg on Cycle 1 Day 1, 200 mg on Cycle 1 Day 2, 400 mg on Cycle 1 Day 3 and daily thereafter;
Phase II: Subjects will receive: AK117: the recommended Phase 2 dose (RP2D) on every two weeks, azacitidine: 75 mg/m^2 on Days 1-7 each cycle, venetoclax: 100 mg on Cycle 1 Day 1, 200 mg on Cycle 1 Day 2, 400 mg on Cycle 1 Day 3 and daily thereafter.
干预措施: Venetoclax (Drug)
Placebo+Azacitidine+Venetoclax
Phase II: Subjects will receive: placebo: the recommended Phase 2 dose (RP2D) on every two weeks, azacitidine: 75 mg/m^2 on Days 1-7 each cycle, venetoclax: 100 mg on Cycle 1 Day 1, 200 mg on Cycle 1 Day 2, 400 mg on Cycle 1 Day 3 and daily thereafter.
干预措施: Azacitidine (Drug)
Placebo+Azacitidine+Venetoclax
Phase II: Subjects will receive: placebo: the recommended Phase 2 dose (RP2D) on every two weeks, azacitidine: 75 mg/m^2 on Days 1-7 each cycle, venetoclax: 100 mg on Cycle 1 Day 1, 200 mg on Cycle 1 Day 2, 400 mg on Cycle 1 Day 3 and daily thereafter.
干预措施: Venetoclax (Drug)
Placebo+Azacitidine+Venetoclax
Phase II: Subjects will receive: placebo: the recommended Phase 2 dose (RP2D) on every two weeks, azacitidine: 75 mg/m^2 on Days 1-7 each cycle, venetoclax: 100 mg on Cycle 1 Day 1, 200 mg on Cycle 1 Day 2, 400 mg on Cycle 1 Day 3 and daily thereafter.
干预措施: Placebo (Other)
结局指标
主要结局
Phase 1b/2: Number of participants with adverse events (AEs)
时间窗: Up to approximately 2 years.
Any untoward medical occurrence in a subject, temporally associated with the use of study treatment, whether or not considered related to the study treatment
Phase 1b/2: Composite complete remission rate (CCR)
时间窗: Time Frame: Up to approximately 2 years
The proportion of subjects achieving complete remission (CR) , complete remission with partial hematologic recovery (CRh) or complete remission with incomplete hematologic recovery (CRi) per European LeukemiaNet (ELN) 2022 criteria
Phase 1b: Number of participants with dose limiting toxicity (DLT)
时间窗: At the end of Cycle 1 (each cycle is 28 days)
Any untoward medical occurrence in a subject within the first cycle, considered related to the study treatment
次要结局
- Time to response (TTR)(Up to approximately 2 years)
- Duration of CCR (DoCCR)(Up to approximately 2 years)
- Event-free survival (EFS)(Up to approximately 2 years)
- Rate of CCR Without Minimal Residual Disease (CCR MRD-)(Up to approximately 2 years)
- Overall survival (OS)(The time from C1D1 until death due to any cause)
- Peak of Serum Concentration (Cmax)(Up to approximately 2 years)
- Duration of response (DoR)(Up to approximately 2 years)
- Overall response rate (ORR)(Up to approximately 2 years)
- Time to CCR (TTCCR)(Up to approximately 2 years)
- Anti-drug antibody (ADA)(Up to approximately 2 years)
- Receptor occupancy (RO)(Up to approximately 2 years)