a study of dual-signaling protein 107 (dsp107) for patients with hematological malignancies

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

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).

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