A Study of AK117 in Combination With Azactidine Plus Venetoclax in Patients With Acute Myeloid Leukemia

Akeso

Status and phase: Not yet enrolling; Phase 2; Phase 1

Conditions: ACUTE MYELOID LEUKEMIA; AML

Treatments: Drug: AK117; Drug: Venetoclax; Other: Placebo; Drug: Azacitidine

Study type: Interventional

Funder types: Industry

Identifiers

NCT06387420

AK117-206

Details and patient eligibility

About

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.

Enrollment: 180 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

180 participants in 2 patient groups, including a placebo group

AK117+Azacitidine+Venetoclax

Experimental group

Description:

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.

Treatment:

Drug: Venetoclax

Drug: AK117

Drug: Azacitidine

Placebo+Azacitidine+Venetoclax

Placebo Comparator group

Description:

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.

Treatment:

Drug: Venetoclax

Other: Placebo

Drug: Azacitidine