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

ACUTE MYELOID LEUKEMIA; AML Clinical Trial

Official title:

A Phase 1b/2 Study of AK117 (Anti-CD47 Antibody) in Combination With Azactidine Plus Venetoclax in Patients With Acute Myeloid Leukemia

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06387420
• Other study ID #: AK117-206
• Status: Not yet recruiting
• Phase: Phase 1/Phase 2
• Start date: April 29, 2024
• Est. completion date: April 2027

Study information

• Verified date: April 2024
• Source: Akeso
• Contact: Jie Yang, MD
• Phone: +86(0760)89873999
• Email: jie.yang[@]akdsobio.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 180
• Est. completion date: April 2027
• Est. primary completion date: April 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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-SIRPa (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.

Related Conditions & MeSH terms

• ACUTE MYELOID LEUKEMIA; AML
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

Drug:
• AK117
Subjects receive AK117 intravenously.
• Azacitidine
Subjects receive azacitidine subcutaneously.
• Venetoclax
Subjects receive venetoclax orally.

Other:
• Placebo
Subjects receive placebo intravenously.

Locations

Country	Name	City	State
China	Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College	Tianjin

Sponsors (1)

Lead Sponsor	Collaborator
Akeso

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase 1b: Number of participants with dose limiting toxicity (DLT)	Any untoward medical occurrence in a subject within the first cycle, considered related to the study treatment	At the end of Cycle 1 (each cycle is 28 days)
Primary	Phase 1b/2: Number of participants with adverse events (AEs)	Any untoward medical occurrence in a subject, temporally associated with the use of study treatment, whether or not considered related to the study treatment	Up to approximately 2 years.
Primary	Phase 1b/2: Composite complete remission rate (CCR)	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	Time Frame: Up to approximately 2 years
Secondary	Overall response rate (ORR)	The proportion of subjects with recorded response per European LeukemiaNet (ELN) 2022	Up to approximately 2 years
Secondary	Time to response (TTR)	Time from cycle 1 day 1(C1D1) to the first recorded response	Up to approximately 2 years
Secondary	Time to CCR (TTCCR)	Time from C1D1 to the first recorded CR, CRh or CRi	Up to approximately 2 years
Secondary	Duration of response (DoR)	Time from the first recorded response until disease progression, relapse, or death due to any cause, whichever occurs first	Up to approximately 2 years
Secondary	Duration of CCR (DoCCR)	Time from the first recorded CR, CRh or CRi until disease progression, relapse, or death due to any cause, whichever occurs first	Up to approximately 2 years
Secondary	Rate of CCR Without Minimal Residual Disease (CCR MRD-)	The proportion of subjects achieving CR, CRh or CRi with MRD-negative status per ELN 2022 criteria.	Up to approximately 2 years
Secondary	Event-free survival (EFS)	Time from C1D1 until disease progression, relapse, or death due to any cause, whichever occurs first	Up to approximately 2 years
Secondary	Overall survival (OS)	Up to approximately 2 years	The time from C1D1 until death due to any cause
Secondary	Peak of Serum Concentration (Cmax)	Maximal serum concentrations of AK117 in individual subjects at different time points after AK117 administration	Up to approximately 2 years
Secondary	Anti-drug antibody (ADA)	Number of subjects with detectable anti-drug antibodies	Up to approximately 2 years
Secondary	Receptor occupancy (RO)	CD47 occupancy rate on peripheral blood T cells and red blood cells before and after AK117 administration	Up to approximately 2 years