Clinical trial NCT06196203: A Study of AK117 in Combination With Azacitidine in Patients With Myelodysplastic Syndromes
Official title: A Randomized, Double-blind, Placebo-controlled, Multicenter Phase 2 Study of AK117/Placebo in Combination With Azacitidine in Patients With Newly Diagnosed Higher-risk Myelodysplastic Syndromes
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Higher-risk Myelodysplastic Syndromes
Lead sponsor: Akeso
Sponsor class: INDUSTRY
First posted: 2024-01-09
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Complete remission rate (CRR)
timeFrame: Up to approximately 2 years
Secondary outcomes:
measure: Overall response rate (ORR)
timeFrame: Up to approximately 2 years
measure: Time to response (TTR)
timeFrame: Up to approximately 2 years
measure: Time to CR (TTCR)
timeFrame: Up to approximately 2 years
measure: Duration of response (DoR)
timeFrame: Up to approximately 2 years
measure: Duration of CR (DoCR)
timeFrame: Up to approximately 2 years
measure: Event-free survival (EFS)
timeFrame: Up to approximately 2 years
measure: Overall survival (OS)
timeFrame: Up to approximately 2 years
measure: Number of subjects with adverse events (AEs)
timeFrame: Up to approximately 2 years
measure: Pharmacokinetic characteristics
timeFrame: Up to approximately 2 years
measure: Anti-drug antibody (ADA)
timeFrame: Up to approximately 2 years
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: UCLA Ronald Reagan Medical Center
state: California
city: Aurora
country: United States
facility: Rocky Mountain Cancer Centers
state: Colorado
city: New Haven
country: United States
facility: Yale Cancer Center
state: Connecticut
city: Orange City
country: United States
facility: Mid Florida Hematology and Oncology Center
state: Florida
city: Bethesda
country: United States
facility: American Oncology Partners, PA (The Center for Cancer and Blood Disorders-Bethesda)
state: Maryland
city: Columbia
country: United States
facility: Maryland Oncology-Columbia
state: Maryland
city: Saint Louis
country: United States
facility: Washington University School of Medicine in St. Louis
state: Missouri
city: Bronx
country: United States
facility: Montefiore Einstein Comprehensive Cancer Center
state: New York
city: Chapel Hill
country: United States
facility: UNC Lineberger Comprehensive Cancer Center
state: North Carolina
city: Canton
country: United States
facility: Gabrail Cancer Center
state: Ohio
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Eugene
country: United States
facility: Oncology Associates of Oregon
state: Oregon
city: Charleston
country: United States
facility: MUSC Hollings Cancer Center
state: South Carolina
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
city: Tianjin
country: China
facility: Institute of hematolongy&blood diseases hospital, chinese academy of medical sciences&peking union medical college
Study officials:
References: