A Study of AK117 in Combination With Azacitidine in Patients With Myelodysplastic Syndromes
- Conditions
- Higher-risk Myelodysplastic Syndromes
- Interventions
- Registration Number
- NCT06196203
- Lead Sponsor
- Akeso
- Brief Summary
This is a Phase 2 randomized, double-blind, placebo-controlled, multicenter study evaluating the efficacy and safety of AK117 or placebo, combined with azacitidine in patients with newly diagnosed higher-risk myelodysplastic syndromes (HR-MDS).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 90
- Age ≥ 18 years old at the time of enrolment.
- Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 2.
- Expected life expectancy ≥ 3 months.
- Newly diagnosed HR-MDS, according to the 2016 World Health Organization (WHO) classification with the presence of < 20% blasts in bone marrow or peripheral blood; Overall IPSS-R score ≥ 3.5.
- Ability to undergo the study-required bone marrow sample collection procedures.
- Suitable venous access for the study-required blood sampling (i.e., including PK and immunogenicity).
- Female patients of childbearing age must have negative serum pregnancy test results before randomization or per region-specific guidance documented in the informed consent and a negative urine pregnancy test on the day of first dose prior to dosing.
- Female patients of childbearing potential having sex with an unsterilized male partner must agree to use a highly effective method of contraception from the beginning of screening until 180 days after the last dose of the study treatment.
- Unsterilized male patients having sex with a female partner of childbearing potential must agree to use an effective method of contraception from the beginning of screening until 180 days after the last dose of study treatment.
- MDS evolving from a pre-existing myeloproliferative neoplasm (MPN), myelodysplastic/myeloproliferative neoplasms (MDS/MPN).
- Prior treatment with Cluster of Differentiation (CD) 47 or Signal-regulatory protein alpha (SIRPα)-targeting agents.
- Concurrently participating in another interventional clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study.
- Patients who previously diagnosed with another malignancy and have any evidence of residual disease.
- Known allergy to any component of any study drug; known history of severe hypersensitivity to other monoclonal antibodies.
- Patients with any psychiatric or social factor which the investigator deems may interfere with the patient's ability to comply with the requirements of the study.
- Patients with current hypertension with systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 100 mmHg after oral antihypertensive therapy.
- 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.
- Patients who are breastfeeding or plans to breastfeed during the study.
- Other conditions where the investigator considers the patient inappropriate for enrollment.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description AK117 (dose 1) in combination with azacitidine Azacitidine Subjects receive AK117 (dose 1) intravenously, in combination with azacitidine (75 mg/m2, D1-7, Q4W) subcutaneously AK117 (dose 2) in combination with azacitidine AK117 Subjects receive AK117 (dose 2) intravenously, in combination with azacitidine (75 mg/m2, D1-7, Q4W) subcutaneously AK117 (dose 1) in combination with azacitidine AK117 Subjects receive AK117 (dose 1) intravenously, in combination with azacitidine (75 mg/m2, D1-7, Q4W) subcutaneously Placebo in combination with azacitidine Placebo Subjects receive placebo intravenously, in combination with azacitidine (75 mg/m2, D1-7, Q4W) subcutaneously AK117 (dose 2) in combination with azacitidine Azacitidine Subjects receive AK117 (dose 2) intravenously, in combination with azacitidine (75 mg/m2, D1-7, Q4W) subcutaneously Placebo in combination with azacitidine Azacitidine Subjects receive placebo intravenously, in combination with azacitidine (75 mg/m2, D1-7, Q4W) subcutaneously
- Primary Outcome Measures
Name Time Method Complete remission rate (CRR) Up to approximately 2 years CRR is defined as the proportion of subjects with complete remission (CR) per International Working Group (IWG) 2023 criteria
- Secondary Outcome Measures
Name Time Method Time to response (TTR) Up to approximately 2 years Time from the randomization to the first recorded response
Duration of CR (DoCR) Up to approximately 2 years Time from the first recorded CR until disease relapse or progression or death due to any cause, whichever occurs first
Duration of response (DoR) Up to approximately 2 years Time from the first recorded response until disease relapse or progression 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 IWG 2023
Event-free survival (EFS) Up to approximately 2 years Time from randomization until transformation to AML or death due to any cause, whichever occurs first
Overall survival (OS) Up to approximately 2 years The time from randomization until death due to any cause
Time to CR (TTCR) Up to approximately 2 years Time from the randomization to the first recorded CR
Number of subjects with adverse events (AEs) Up to approximately 2 years An AE is any untoward medical occurrence in a subject, temporally associated with the use of study treatment, whether or not considered related to the study treatment
Pharmacokinetic characteristics Up to approximately 2 years 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
Trial Locations
- Locations (15)
Mid Florida Hematology and Oncology Center
🇺🇸Orange City, Florida, United States
UCLA Ronald Reagan Medical Center
🇺🇸Los Angeles, California, United States
American Oncology Partners, PA (The Center for Cancer and Blood Disorders-Bethesda)
🇺🇸Bethesda, Maryland, United States
Washington University School of Medicine in St. Louis
🇺🇸Saint Louis, Missouri, United States
Montefiore Einstein Comprehensive Cancer Center
🇺🇸Bronx, New York, United States
Ohio State University
🇺🇸Columbus, Ohio, United States
MUSC Hollings Cancer Center
🇺🇸Charleston, South Carolina, United States
Institute of hematolongy&blood diseases hospital, chinese academy of medical sciences&peking union medical college
🇨🇳Tianjin, China
Rocky Mountain Cancer Centers
🇺🇸Aurora, Colorado, United States
Oncology Associates of Oregon
🇺🇸Eugene, Oregon, United States
UT Southwestern Medical Center
🇺🇸Dallas, Texas, United States
Yale Cancer Center
🇺🇸New Haven, Connecticut, United States
Maryland Oncology-Columbia
🇺🇸Columbia, Maryland, United States
UNC Lineberger Comprehensive Cancer Center
🇺🇸Chapel Hill, North Carolina, United States
Gabrail Cancer Center
🇺🇸Canton, Ohio, United States