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

NCT06387420 | Not Yet Recruiting Phase 1

• 1 other identifier: AK117-206
• Study Type: interventional
• Target: 180
• Locations: 1 country
• Sites: 1

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.

Conditions

ACUTE MYELOID LEUKEMIA; AML

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (11)

• Overall response rate (ORR)

  Up to approximately 2 years

• Time to response (TTR)

  Up to approximately 2 years

• Time to CCR (TTCCR)

  Up to approximately 2 years

• Duration of response (DoR)

  Up to approximately 2 years

• Duration of CCR (DoCCR)

  Up to approximately 2 years

Study Arms (2)

AK117+Azacitidine+Venetoclax

EXPERIMENTAL

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; Drug: Azacitidine; Drug: Venetoclax

Placebo+Azacitidine+Venetoclax

PLACEBO COMPARATOR

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; Drug: Venetoclax; Other: Placebo

Interventions

AK117 DRUG

Subjects receive AK117 intravenously.

AK117+Azacitidine+Venetoclax

Azacitidine DRUG

Subjects receive azacitidine subcutaneously.

AK117+Azacitidine+Venetoclax; Placebo+Azacitidine+Venetoclax

Venetoclax DRUG

Subjects receive venetoclax orally.

AK117+Azacitidine+Venetoclax; Placebo+Azacitidine+Venetoclax

Placebo OTHER

Subjects receive placebo intravenously.

Placebo+Azacitidine+Venetoclax

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Akeso: lead

Study Sites (1)

Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College

Tianjin, China

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Azacitidine; venetoclax

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Central Study Contacts

Jie Yang, MD

CONTACT

+86(0760)89873999; jie.yang@akdsobio.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 24, 2024
• First Posted: April 29, 2024
• Study Start: April 29, 2024
• Primary Completion: April 1, 2026
• Study Completion (Estimated): April 1, 2027
• Last Updated: April 29, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)