A Study of AK117 in Combination With Azactidine Plus Venetoclax in Patients With Acute Myeloid Leukemia
- Conditions
- ACUTE MYELOID LEUKEMIA; AML
- Interventions
- Registration Number
- NCT06387420
- Lead Sponsor
- Akeso
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 180
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description AK117+Azacitidine+Venetoclax 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. Placebo+Azacitidine+Venetoclax Placebo 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. AK117+Azacitidine+Venetoclax AK117 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. AK117+Azacitidine+Venetoclax Azacitidine 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. Placebo+Azacitidine+Venetoclax 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. Placebo+Azacitidine+Venetoclax Azacitidine 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.
- Primary Outcome Measures
Name Time Method Phase 1b/2: Number of participants with adverse events (AEs) 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) 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) 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
- Secondary Outcome Measures
Name Time Method Time to response (TTR) Up to approximately 2 years Time from cycle 1 day 1(C1D1) to the first recorded response
Duration of CCR (DoCCR) Up to approximately 2 years Time from the first recorded CR, CRh or CRi until disease progression, relapse, or death due to any cause, whichever occurs first
Event-free survival (EFS) Up to approximately 2 years Time from C1D1 until disease progression, relapse, or death due to any cause, whichever occurs first
Rate of CCR Without Minimal Residual Disease (CCR MRD-) Up to approximately 2 years The proportion of subjects achieving CR, CRh or CRi with MRD-negative status per ELN 2022 criteria.
Overall survival (OS) The time from C1D1 until death due to any cause Up to approximately 2 years
Peak of Serum Concentration (Cmax) Up to approximately 2 years Maximal serum concentrations of AK117 in individual subjects at different time points after AK117 administration
Duration of response (DoR) Up to approximately 2 years Time from the first recorded response until disease progression, relapse, or death due to any cause, whichever occurs first
Overall response rate (ORR) Up to approximately 2 years The proportion of subjects with recorded response per European LeukemiaNet (ELN) 2022
Time to CCR (TTCCR) Up to approximately 2 years Time from C1D1 to the first recorded CR, CRh or CRi
Anti-drug antibody (ADA) Up to approximately 2 years Number of subjects with detectable anti-drug antibodies
Receptor occupancy (RO) Up to approximately 2 years CD47 occupancy rate on peripheral blood T cells and red blood cells before and after AK117 administration
Trial Locations
- Locations (1)
Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College
🇨🇳Tianjin, China