ACUTE MYELOID LEUKEMIA; AML
Conditions
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.
Interventions
DRUGAK117
Subjects receive AK117 intravenously.
DRUGAzacitidine
Subjects receive azacitidine subcutaneously.
DRUGVenetoclax
Subjects receive venetoclax orally.
OTHERPlacebo
Subjects receive placebo intravenously.
Sponsors
Akeso
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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.
Exclusion criteria
* 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
| 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. |
| 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 |
| Overall response rate (ORR) | Up to approximately 2 years | The proportion of subjects with recorded response per European LeukemiaNet (ELN) 2022 |
| 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 |
| 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 |
| Overall survival (OS) | The time from C1D1 until death due to any cause | Up to approximately 2 years |
| Time to response (TTR) | Up to approximately 2 years | Time from cycle 1 day 1(C1D1) to the first recorded response |
| Time to CCR (TTCCR) | Up to approximately 2 years | Time from C1D1 to the first recorded CR, CRh or CRi |
Countries
China
Contacts
Primary ContactJie Yang, MD
Outcome results
None listed