Cusatuzumab in Combination With Background Therapy for the Treatment of Participants With Acute Myeloid Leukemia

Study Overview
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Brief Summary
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The purpose of the study is to characterize safety and tolerability of cusatuzumab in combination with various therapies used to treat acute myeloid leukemia (AML).

Official Title
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An Open-label, Multicenter, Phase 1b Study of OV-1001 (Cusatuzumab; Anti-CD70 Monoclonal Antibody) in Combination With Background Therapy for the Treatment of Subjects With Acute Myeloid Leukemia

Conditions
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Leukemia, Myeloid, Acute

Intervention / Treatment
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* Drug: Cusatuzumab
* Drug: Azacitidine
* Drug: Venetoclax


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of acute myeloid leukemia (AML) according to World Health Organization 2016 criteria . Participants with acute promyelocytic leukemia (APL) are not eligible Must be ineligible for intensive chemotherapy De novo or secondary AML Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 Previously untreated AML except: emergency leukapheresis, hydroxyurea, and/or 1 dose 1-2 gram per meter square (g/m^2) cytarabine during the Screening Phase to control hyperleukocytosis. These treatments must be discontinued greater than or equal to (>=) 24 hours prior to start of study drug. Empiric all trans retinoic acid (ATRA) treatment for presumed acute promyelocytic leukemia (APL) is permitted but APL must be ruled out and ATRA must be discontinued >=24 hours prior to the start of study drug Contraceptive use by men or women should be consistent with local regulations regarding the use of contraceptive methods for participants participating in clinical studies Exclusion Criteria: Leukemic involvement of the central nervous system Eligible for an allogeneic hematopoietic stem cell transplantation at study entry Received a live, attenuated vaccine within 4 weeks prior to initiation of study drug A history of human immunodeficiency virus (HIV) antibody positive or tests positive for HIV if tested at screening Known allergies, hypersensitivity, or intolerance to cusatuzumab, venetoclax, azacitidine, or their excipients (example: mannitol, an excipient of azacitidine)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental: Cohort 2: Cusatuzumab + Venetoclax<br>Participants enrolled in this cohort will receive venetoclax ramp-up to 400 mg orally (as background therapy) starting on Cycle 1 Day 1 and followed by 400 mg daily dosing starting on Cycle 1 Day 4 plus cusatuzumab IV on Day 3 and Day 17 of each 28-day cycle. Cohort 2 will not be enrolled in the US. | Drug: Cusatuzumab<br>* Cusatuzumab will be administered as a dose of 10mg/kg or 20mg/kg intravenously.<br>* Other names: ARGX-110;Drug: Venetoclax<br>* Venetoclax will be administered orally and the dose will ramp-up to 400 mg.<br>* Other names: Venclexta;|
| Experimental: Cohort 3: Cusatuzumab + Venetoclax + Azacitidine (CVA)<br>Participants enrolled at US sites will receive cusatuzumab 10 mg/kg and potentially escalate to 20 mg/kg IV in combination with azacitidine 75 mg/m^2 SC or IV plus venetoclax ramp-up to 400 mg orally (as background therapies). Participants enrolled from ex-US sites will receive cusatuzumab 20 mg/kg and potentially de-escalate to 10 mg/kg IV in combination with azacitidine 75 mg/m^2 SC or IV plus venetoclax ramp-up to 400 mg orally (as background therapies). | Drug: Cusatuzumab<br>* Cusatuzumab will be administered as a dose of 10mg/kg or 20mg/kg intravenously.<br>* Other names: ARGX-110;Drug: Azacitidine<br>* Azacitidine will be administered 75 mg/m^2 subcutaneously or intravenously.<br>* Other names: Vidaza;Drug: Venetoclax<br>* Venetoclax will be administered orally and the dose will ramp-up to 400 mg.<br>* Other names: Venclexta;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency and Severity of Adverse Events (AEs), Laboratory Abnormalities, and Physical Exam Findings as a Measure of Safety | Frequency and severity of AEs, laboratory abnormalities, and physical exam findings will be reported. | Up to 42 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum Concentration of Cusatuzumab | Serum concentration of cusatuzumab will be assessed. | Up to 23 months | 
| Number of Participants with Anti-cusatuzumab Antibodies | Number of participants with anti-drug antibodies to cusatuzumab will be reported. | Up to 23 months | 
| Percentage of Participants with Complete Response (CR) | Percentage of participants with complete response based on European Leukemia Network (ELN) 2017 response criteria assessment will be reported. | Up to 42 months | 
| Percentage of Participants with Complete Remission with Partial Hematological Recovery (CRh) | Percentage of participants with CRh will be reported based on ELN 2017 response criteria assessment. | Up to 42 months | 
| Percentage of Participants with CR with Incomplete Recovery (CRi) | Percentage of participants with CRi will be reported based on ELN 2017 response criteria assessment. | Up to 42 months | 
| Percentage of Participants with CR plus CRh | Percentage of participants with CR plus CRh will be reported based on ELN 2017 response criteria assessment. | Up to 42 months | 
| Overall Response Rate (ORR) | ORR is defined as percentage of participants with CR, CRh and CRi based on ELN 2017 response criteria assessment. | Up to 42 months | 
| Percentage of Participants with CR without MRD | Percentage of participants with CR without minimal residual disease (MRD) will be reported and is defined as less than (<) 1 blast or leukemic stem cell in 1,000 leukocytes (MRD level <10^-3). | Up to 42 months | 
| Percentage of Participants with Negative MRD who Achieved CR, CRh, CRi, or Morphologic Leukemia-free State (MLFS) | Percentage of participants with negative MRD who achieved CR, CRh, CRi, or MLFS will be reported and is defined as < 1 blast or leukemic stem cell in 1,000 leukocytes (MRD level <10^-3). | Up to 42 months | 
| Cohort 2 and 3: Time to Response | Time to response is defined as time from first dose to achieving the first response of CR, CRh, or CRi. | Up to 42 months | 
| Cohort 2 and 3: Duration of Response | Duration of response is defined as time from achieving the first response of CR, CRh, or CRi to hematologic relapse or death of any cause. | Up to 42 months | 
| Cohort 2 and 3: Red Blood Cell (RBC) or Platelet Transfusion Independence | Transfusion independence (RBC or platelets) is defined as a period of greater than or equal to (>=) 56 consecutive days with no transfusion between first dose of study drug and the last dose of study drug +30 days. | Up to 42 months |