Clinical trial NCT06387420: A Study of AK117 in Combination With Azactidine Plus Venetoclax in Patients With Acute Myeloid Leukemia
Official title: A Phase 1b/2 Study of AK117 (Anti-CD47 Antibody) in Combination With Azactidine Plus Venetoclax in Patients With Acute Myeloid Leukemia
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
PHASE2
Conditions: ACUTE MYELOID LEUKEMIA; AML
Lead sponsor: Akeso
Sponsor class: INDUSTRY
First posted: 2024-04-29
Enrollment: 180
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 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Phase 1b: Number of participants with dose limiting toxicity (DLT)
timeFrame: At the end of Cycle 1 (each cycle is 28 days)
measure: Phase 1b/2: Number of participants with adverse events (AEs)
timeFrame: Up to approximately 2 years.
measure: Phase 1b/2: Composite complete remission rate (CCR)
timeFrame: Time Frame: 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 CCR (TTCCR)
timeFrame: Up to approximately 2 years
measure: Duration of response (DoR)
timeFrame: Up to approximately 2 years
measure: Duration of CCR (DoCCR)
timeFrame: Up to approximately 2 years
measure: Rate of CCR Without Minimal Residual Disease (CCR MRD-)
timeFrame: Up to approximately 2 years
measure: Event-free survival (EFS)
timeFrame: Up to approximately 2 years
measure: Overall survival (OS)
timeFrame: The time from C1D1 until death due to any cause
measure: Peak of Serum Concentration (Cmax)
timeFrame: Up to approximately 2 years
measure: Anti-drug antibody (ADA)
timeFrame: Up to approximately 2 years
measure: Receptor occupancy (RO)
timeFrame: Up to approximately 2 years
Other outcomes:
Locations:
city: Tianjin
country: China
facility: Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College
Study officials:
References: