This study will be divided into two parts, Parts A and B and will enroll patients with relapsed/refractory AML or MDS/chronic myelomonocytic leukemia (CMML) patients who have failed up to 2 prior therapeutic regimens. Part A is a dose escalation study to explore the safety, efficacy, pharmacokinetic (PK) and pharmacodynamic (PD) profile of DSP107 when administered in combination with azacitidine (AZA). Part B is a dose escalation study to explore the safety, efficacy, PK and PD profile of DSP107 when administered in combination with AZA and venetoclax (VEN).
Part A is a dose escalation study in up to 4 cohorts of patients designed to test the safety and efficacy of DSP107 administered alone and in combination with AZA. The DSP107 starting dose level in Part A will be 0.3 mg/kg based on aggregate safety, PK and PD data from study DSP107\_001, an ongoing study exploring the safety of escalating DSP107 doses in patients with advanced solid tumors. There will be a single DLT evaluation period, lasting 28 days, to determine the safety of DSP107 in combination with AZA. The safety, efficacy and PK data will be used to establish a recommended Phase II dose for potential future expansion cohorts and a starting dose for Part B. Part B is a dose escalation study in 2 cohorts of patients that will test the safety and efficacy of DSP107 in combination with AZA and VEN. The starting dose for Part B will be at least one dose level lower than the DSP107 dose selected in Part A as being safe and effective in combination with AZA. Once a safe, effective dose has been established in Part B, a recommended phase 2 dose for patients with newly diagnosed AML will be agreed with the FDA at an End-of-Phase 1 meeting.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
25
DSP107 (SIRPα - 4-1BBL) is a bi-functional, trimeric, fusion protein.
Azacitidine is an analog of the pyrimidine nucleoside cytidine.
Venetoclax is a B-cell lymphoma (BCL)-2 inhibitor
City of Hope
Duarte, California, United States
The University of Texas MD Anderson Cancer Center, Department of Leukemia
Houston, Texas, United States
Adverse Events (AEs)
An AE is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.
Time frame: Duration of the study, estimated to be 12 months
Dose Limiting Toxicities (DLT)
A DLT is defined as a clinically significant AE or laboratory abnormality that is related to DSP107 or the combination of DSP107 and AZA, but is unrelated to disease progression, intercurrent illness or concomitant medications
Time frame: At the end of Treatment Cycle 2 (within 2 months of treatment initiation)
Response Rate (RR) including Complete Remission (CR) and Complete Remission with Incomplete Blood Count Recovery (CRi)
Response rates will be determined by assessing peripheral blood and bone marrow samples.
Time frame: Within 6 months of treatment initiation
Overall Response Rate (ORR)
Peripheral and bone marrow samples will be assessed to determine ORR. The ORR will measure the proportion of patients who achieve CR, CRi, complete remission with incomplete hematological recovery (CRh), complete remission with incomplete platelet recovery (CRp) or partial response (PR) within 6 months of treatment initiation, with or without cytogenetic response, hematological improvements and a morphologic leukemia-free state.
Time frame: Within 6 months of treatment initiation
Morphologic Leukemia-Free (MLF) Rate
Peripheral and bone marrow samples will be assessed to determine the proportion of patients who are morphologically leukemia-free within 6 months of treatment initiation.
Time frame: Within 6 months of treatment initiation
Minimal Residual Disease (MRD) Status
Peripheral and bone marrow samples will be assessed to determine minimal residual disease (MRD) status at response and/or the best MRD response during study participation.
Time frame: Duration of the study, estimated to be 12 months
4-week Mortality Rate
The proportion of patients who die within 4 weeks of treatment initiation.
Time frame: Within 4 weeks of treatment initiation
DSP107 Serum Concentration
Serum samples will be collected to determine circulating levels of DSP107.
Time frame: Duration of the study, estimated to be 12 months
DSP107 anti-drug antibody (ADA) formation
Serum samples will be collected throughout the study for assessment of ADA formation using validated assay.
Time frame: Duration of the study, estimated to be 12 months
Change in Phenotypic and Activation Profiles of Peripheral Blood Mononuclear Cells
Whole blood samples will be collected throughout the study for immunophenotyping by flow cytometry and/or mass cytometry.
Time frame: Duration of the study, estimated to be 12 months
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