Clinical trial NCT04937166: 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
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Acute Myeloid Leukemia
Myelodysplastic Syndromes
Chronic Myelomonocytic Leukemia
Lead sponsor: Kahr Medical
Sponsor class: INDUSTRY
First posted: 2021-06-23
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Intervention 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).
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Adverse Events (AEs)
timeFrame: Duration of the study, estimated to be 12 months
measure: Dose Limiting Toxicities (DLT)
timeFrame: At the end of Treatment Cycle 2 (within 2 months of treatment initiation)
measure: Response Rate (RR) including Complete Remission (CR) and Complete Remission with Incomplete Blood Count Recovery (CRi)
timeFrame: Within 6 months of treatment initiation
Secondary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: Within 6 months of treatment initiation
measure: Morphologic Leukemia-Free (MLF) Rate
timeFrame: Within 6 months of treatment initiation
measure: Minimal Residual Disease (MRD) Status
timeFrame: Duration of the study, estimated to be 12 months
measure: 4-week Mortality Rate
timeFrame: Within 4 weeks of treatment initiation
measure: DSP107 Serum Concentration
timeFrame: Duration of the study, estimated to be 12 months
measure: DSP107 anti-drug antibody (ADA) formation
timeFrame: Duration of the study, estimated to be 12 months
measure: Change in Phenotypic and Activation Profiles of Peripheral Blood Mononuclear Cells
timeFrame: Duration of the study, estimated to be 12 months
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope
state: California
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center, Department of Leukemia
state: Texas
Study officials:
References: