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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: ACUTE MYELOID LEUKEMIA; AML
• Intervention / Treatment: Drug: AK117; Drug: Azacitidine; Drug: Venetoclax; Other: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 180
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Jie Yang, MD; Phone Number: +86(0760)89873999; Email: jie.yang@akdsobio.com

Study Locations

• China
  • Tianjin, China
    • Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College
    • Contact: Jianxiang Wang

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: AK117; Subjects receive AK117 intravenously.; Drug: Azacitidine; Subjects receive azacitidine subcutaneously.; Drug: Venetoclax; Subjects receive venetoclax orally.
Placebo Comparator: 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.	Drug: Azacitidine; Subjects receive azacitidine subcutaneously.; Drug: Venetoclax; Subjects receive venetoclax orally.; Other: Placebo; Subjects receive placebo intravenously.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
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.
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anti-drug antibody (ADA)	Number of subjects with detectable anti-drug antibodies	Up to approximately 2 years
Overall response rate (ORR)	The proportion of subjects with recorded response per European LeukemiaNet (ELN) 2022	Up to approximately 2 years
Time to response (TTR)	Time from cycle 1 day 1(C1D1) to the first recorded response	Up to approximately 2 years
Time to CCR (TTCCR)	Time from C1D1 to the first recorded CR, CRh or CRi	Up to approximately 2 years
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
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
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
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
Overall survival (OS)	Up to approximately 2 years	The time from C1D1 until death due to any cause
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
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

Collaborators and Investigators

• Sponsor: Akeso

Study record dates

Study Major Dates

• Study Start (Estimated): April 29, 2024
• Primary Completion (Estimated): April 1, 2026
• Study Completion (Estimated): April 1, 2027

Study Registration Dates

• First Submitted: April 24, 2024
• First Submitted That Met QC Criteria: April 24, 2024
• First Posted (Actual): April 29, 2024

Study Record Updates

• Last Update Posted (Actual): April 29, 2024
• Last Update Submitted That Met QC Criteria: April 24, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Venetoclax; Azacitidine
• Other Study ID Numbers: AK117-206

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No