A Study of Dual-SIgnaling Protein 107 (DSP107) for Patients With Hematological Malignancies

Kahr Medical

Status and phase: Terminated; Phase 1

Conditions: Myelodysplastic Syndromes; Acute Myeloid Leukemia; Chronic Myelomonocytic Leukemia

Treatments: Drug: Azacitidine; Drug: Venetoclax; Biological: DSP107

Study type: Interventional

Funder types: Industry

Identifiers

NCT04937166

DSP107_002

Details and patient eligibility

About

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).

Full 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.

Enrollment: 25 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Sequential Assignment

Masking: None (Open label)

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25 participants in 1 patient group

DSP107 in combination with azacitidine or azacitidine plus venetoclax.

Experimental group

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.

Treatment:

Biological: DSP107

Drug: Venetoclax

Drug: Azacitidine