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

An Open-label Phase Ib Study of DSP107 for Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS)

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.

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