SNS-301 Monotherapy in High Risk MDS and CMML

Study Overview
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Brief Summary
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To evaluate safety, immunogenicity and anti-tumor responses of intradermally delivered SNS-301 in patients with ASPH+ high risk MDS and CMML.

Detailed Description
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This phase 2, open-label, multi-center trial to evaluate the safety, immunogenicity and preliminary clinical efficacy of intradermally-delivered SNS-301 delivered using the 3M® hollow microstructured transdermal system (hMTS) device in patients with ASPH+ high risk myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML). The trial population consists of high risk ≥ Intermediate Risk-3 (IR-3) MDS and CMML-2.

Official Title
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An Open-Label, Multi-Center Phase 2 Clinical Trial Evaluating SNS-301 in Patients With ASPH+ High Risk Myelodysplastic Syndrome and Chronic Myelomonocytic Leukemia

Conditions
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Myelodysplastic Syndromes, Chronic Myelomonocytic Leukemia (CMML)

Intervention / Treatment
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* Drug: SNS-301


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent. Be 18 years of age or older. Confirmed diagnosis of MDS or CMML. Assessment of high-risk-MDS/CMML status defined as follows: MDS: IPSS-R criteria for categorization ≥ Intermediate Risk-3 CMML: WHO criteria for CMML-2 (peripheral blasts of 5% to 19%, and 10% to 19% bone marrow blasts and/or presence of Auer rods). Be willing to provide a fresh bone marrow aspirate sample at pre-treatment and demonstrate ASPH expression by flow cytometry. Patient who has relapsed or is refractory / intolerant of hypomethylating agents (HMAs) or not responding to 4 treatment cycles of decitabine or 6 treatment cycles of azacytidine or progressing at any point after initiation of an HMA. Patient refuses or is not considered a candidate for intensive induction chemotherapy using consensus criteria for defining such patients. Patients with CMML must have been treated with at least 1 prior therapy (hydroxyurea or an HMA). Eastern Cooperative Oncology Group (ECOG) Performance Scale 0-1. Demonstrate adequate organ function: renal, hepatic, coagulation parameters. For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use two highly effective contraceptive methods during the treatment period and for at least 180 days after the last dose of study treatment. For male patients: Agree that during the period specified above, men will not father a child. Male patients must remain abstinent, must be surgically sterile during the treatment period and for at least 180 days after the last dose of study treatment. Exclusion Criteria: Any approved anti-cancer therapy including chemotherapy, targeted small molecule therapy or radiation therapy within 2 weeks prior to trial Day 0. Participated on a clinical trial of an investigational agent and/or investigational device within 28 days prior to Day 0. Malignancies other than indications open for enrollment within 3 years prior to Day 0. Diagnosis of a core binding factor leukemia (t(8;21), t(16;16); or inv(16)) or diagnosis of acute promyelocytic leukemia (t(15;17)). Active or history of autoimmune disease or immune deficiency. History of HIV. HIV antibody testing recommended per investigator's clinical suspicion. Active hepatitis B (hepatitis B surface antigen reactive) or active hepatitis C (HCV qualitative RNA detected); testing recommended per investigator's clinical suspicion. Severe infections within 4 weeks prior to enrollment. Received therapeutic oral or IV antibiotics within 2 weeks prior to Day 0. History or current evidence of any condition, therapy or laboratory abnormality that in the opinion of the treating investigator might confound the results of the trial. Known previous or ongoing, active psychiatric or substance abuse disorders that would interfere with the requirements of the trial. Treatment with systemic immunomodulating agents (including but not limited to IFNs, IL-2) within 6 weeks or five half-lives of the drug, whichever is shorter, prior to first dose. Treatment with systemic immunosuppressive medication within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during the course of the study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SNS-301<br>SNS-301 | Drug: SNS-301<br>* SNS-301 (1x 1011 dose/1ml) ID injection every 3 weeks for 4 doses then every 6 weeks for 6 additional doses, and thereafter every 12 weeks up to 24 months.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events of SNS-301 | Number of adverse events including adverse events of special interest as assessed by CTCAE v5.0 | 12 weeks | 
| Objective response rate by International Working Group (IWG) 2006 criteria | Best objective response during the study | 12 weeks | 
| Minimal residual disease by IWG 2006 criteria | Minimal residual disease by peripheral and bone marrow blast count during the study | 12 weeks | 
| Duration of Response by IWG 2006 criteria | Duration of response calculated from date of first response to date of progression | 12 weeks | 
| Disease control rate (DCR) by IWG 2006 criteria | Disease control rate calculated as the proportion of patients with stable disease or better | 12 weeks | 
| Progression Free Survival (PFS) as assessed by IWG 2006 criteria | Progression free survival calculated from the date of start of treatment to date of progression | 12 weeks | 
| Overall Survival | Overall survival calculated from date of treatment to date of death | 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measurement of ASPH specific responses | Evaluate blood and tissue ASPH-specific responses at pretreatment, changes during treatment and at progression or end of study in all study participants where sample is available for analysis | up to 12 weeks | 
| Measurement of T cell immune response | Characterize blood and bone marrow T cell types and numbers at pretreatment, changes during treatment and at progression or end of study in all study participants where sample is available for analysis | up 12 weeks | 
| Measurement B cell immune responses | Characterize blood and bone marrow B cell numbers at pretreatment, changes during treatment and at progression or end of study in all study participants where sample is available for analyses | up to 12 weeks | 
| Evaluation of immune gene transcript profiles | Determine changes in commercially available gene signature panels in blood and bone marrow pretreatment, during treatment and at progression in all study participants where sample is available for analysis | up to12 weeks | 
| Measurement of pro-inflammatory and/or immunosuppressive molecules | The immunological response of pro-inflammatory/immunosuppressive molecules will be observed before, during and after treatment using commercially available assays. Analyses will be performed both on blood and bone marrow samples in all study participants where sample is available for analysis | up to 12 weeks | 
| Measurement of oncoprotein expression | Changes in oncoprotein levels will be evaluated before, during and after treatment using methods such as flow cytometry. Analyses will be performed both on blood and bone marrow samples in all study participants where sample is available for analysis | up to 12 weeks |