Back to resultsA Study of Dual-SIgnaling Protein 107 (DSP107) for Patients With Hematological Malignancies
Primary Purpose
Acute Myeloid Leukemia, Myelodysplastic Syndromes, Chronic Myelomonocytic Leukemia
Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
DSP107
Azacitidine
Venetoclax
Sponsored by
About this trial
This is an interventional treatment trial for Acute Myeloid Leukemia
Eligibility Criteria
Inclusion Criteria:
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2
- White Blood Cell count < 20 x 10^9/L.
- Adequate organ function
- Relapsed/refractory AML or MDS/CMML patients who have failed up to 2 prior therapeutic regimens.
Exclusion Criteria:
- Acute Promyelocytic leukemia
- Symptomatic central nervous system (CNS) leukemia or patients with poorly controlled CNS leukemia
- Life-threatening (grade 4) immune-mediated adverse event related to prior immunotherapy
- Immune-mediated adverse reaction that required discontinuation of prior immunotherapy
- Past or current history of autoimmune disease or immune deficiency
- History of severe interstitial lung disease or severe pneumonitis or active pneumonitis
- Clinically significant and poorly compensated liver disease
- Prior organ allografts (such as renal transplant) requiring active immunosuppression
- Active graft versus host disease
- Treatment with systemic immunostimulatory within 4 weeks prior to initiation of study treatment
- Treatment with any CD47/SIRPα targeting agent or immune agonists
- Known allergy or hypersensitivity to any of the test compounds, materials or contraindication to test product
- Received live, attenuated vaccine within 4 weeks prior to first dose of study treatment
- Active Hepatitis B or C infection
- History or evidence of any other clinically unstable/uncontrolled disorder, condition, or disease
- Pregnant or breast feeding or planning to become pregnant while enrolled in the study
Sites / Locations
- The University of Texas MD Anderson Cancer Center, Department of LeukemiaRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
DSP107 in combination with azacitidine or azacitidine plus venetoclax.
Arm Description
DSP107 will be administered by intravenous infusion once weekly during each 28-day cycle to all patients in this study. Azacitidine (75 mg/m2/day) will be administered subcutaneously or intravenously for the first 7 days of every cycle. Patients enrolled in Part B only will also receive venetoclax. During Cycle 1, venetoclax will be dose escalated daily to the goal dose of 400 mg daily. Patients will receive 100 mg on Day 1, 200 mg on Day 2 and 400 mg on Day 3 and onwards.
Outcomes
Primary Outcome Measures
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.
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
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.
Secondary Outcome Measures
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.
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.
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.
4-week Mortality Rate
The proportion of patients who die within 4 weeks of treatment initiation.
DSP107 Serum Concentration
Serum samples will be collected to determine circulating levels of DSP107.
DSP107 anti-drug antibody (ADA) formation
Serum samples will be collected throughout the study for assessment of ADA formation using validated assay.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04937166
Brief Title
A Study of Dual-SIgnaling Protein 107 (DSP107) for Patients With Hematological Malignancies
Official Title
An Open-label Phase Ib Study of DSP107 for Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS)
Study Type
Interventional
2. Study Status
Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
January 13, 2022 (Actual)
Primary Completion Date
August 2024 (Anticipated)
Study Completion Date
December 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Kahr Medical
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
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).
Detailed Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myeloid Leukemia, Myelodysplastic Syndromes, Chronic Myelomonocytic Leukemia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Model Description
This study will involve sequential enrollment of approximately 36 patients accrued into six dose cohorts, each testing a different DSP107 dose level in combination with azacitidine (Part A) or DSP107 in combination with azacitidine and venetoclax (Part B).
Masking
None (Open Label)
Allocation
N/A
Enrollment
36 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
DSP107 in combination with azacitidine or azacitidine plus venetoclax.
Arm Type
Experimental
Arm Description
DSP107 will be administered by intravenous infusion once weekly during each 28-day cycle to all patients in this study.
Azacitidine (75 mg/m2/day) will be administered subcutaneously or intravenously for the first 7 days of every cycle.
Patients enrolled in Part B only will also receive venetoclax. During Cycle 1, venetoclax will be dose escalated daily to the goal dose of 400 mg daily. Patients will receive 100 mg on Day 1, 200 mg on Day 2 and 400 mg on Day 3 and onwards.
Intervention Type
Biological
Intervention Name(s)
DSP107
Intervention Description
DSP107 (SIRPα - 4-1BBL) is a bi-functional, trimeric, fusion protein.
Intervention Type
Drug
Intervention Name(s)
Azacitidine
Other Intervention Name(s)
Vidaza
Intervention Description
Azacitidine is an analog of the pyrimidine nucleoside cytidine.
Intervention Type
Drug
Intervention Name(s)
Venetoclax
Other Intervention Name(s)
Venclexta, Venclyxto
Intervention Description
Venetoclax is a B-cell lymphoma (BCL)-2 inhibitor
Primary Outcome Measure Information:
Title
Adverse Events (AEs)
Description
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
Title
Dose Limiting Toxicities (DLT)
Description
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)
Title
Response Rate (RR) including Complete Remission (CR) and Complete Remission with Incomplete Blood Count Recovery (CRi)
Description
Response rates will be determined by assessing peripheral blood and bone marrow samples.
Time Frame
Within 6 months of treatment initiation
Secondary Outcome Measure Information:
Title
Overall Response Rate (ORR)
Description
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
Title
Morphologic Leukemia-Free (MLF) Rate
Description
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
Title
Minimal Residual Disease (MRD) Status
Description
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
Title
4-week Mortality Rate
Description
The proportion of patients who die within 4 weeks of treatment initiation.
Time Frame
Within 4 weeks of treatment initiation
Title
DSP107 Serum Concentration
Description
Serum samples will be collected to determine circulating levels of DSP107.
Time Frame
Duration of the study, estimated to be 12 months
Title
DSP107 anti-drug antibody (ADA) formation
Description
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
Title
Change in Phenotypic and Activation Profiles of Peripheral Blood Mononuclear Cells
Description
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2
White Blood Cell count < 20 x 10^9/L.
Adequate organ function
Relapsed/refractory AML or MDS/CMML patients who have failed up to 2 prior therapeutic regimens.
Exclusion Criteria:
Acute Promyelocytic leukemia
Symptomatic central nervous system (CNS) leukemia or patients with poorly controlled CNS leukemia
Life-threatening (grade 4) immune-mediated adverse event related to prior immunotherapy
Immune-mediated adverse reaction that required discontinuation of prior immunotherapy
Past or current history of autoimmune disease or immune deficiency
History of severe interstitial lung disease or severe pneumonitis or active pneumonitis
Clinically significant and poorly compensated liver disease
Prior organ allografts (such as renal transplant) requiring active immunosuppression
Active graft versus host disease
Treatment with systemic immunostimulatory within 4 weeks prior to initiation of study treatment
Treatment with any CD47/SIRPα targeting agent or immune agonists
Known allergy or hypersensitivity to any of the test compounds, materials or contraindication to test product
Received live, attenuated vaccine within 4 weeks prior to first dose of study treatment
Active Hepatitis B or C infection
History or evidence of any other clinically unstable/uncontrolled disorder, condition, or disease
Pregnant or breast feeding or planning to become pregnant while enrolled in the study
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Yaffa Shwartz
Phone
+972-50-6396356
Email
yaffa@kahrbio.com
Facility Information:
Facility Name
The University of Texas MD Anderson Cancer Center, Department of Leukemia
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Crystal Landeros, M.S.
Phone
713-745-7710
Email
cemorales@mdanderson.org
First Name & Middle Initial & Last Name & Degree
Naval Daver, Prof.
12. IPD Sharing Statement
Learn more about this trial
A Study of Dual-SIgnaling Protein 107 (DSP107) for Patients With Hematological Malignancies
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