A Phase I/II Study of OPN-305 in Second-line Lower Risk Myelodysplastic Syndrome

Inclusion Criteria:

* Written informed consent
* Age ≥ 18 years
* Diagnosis of MDS (de novo or secondary) by bone marrow aspirate based on the World Health Organization (WHO) classification - Low and Intermediate-1 risk categories MDS using the IPSS (International Prognostic Scoring System)
* AZA/decitabine (this applies to standard of care and investigational drugs) failure (Dose confirming and Dose expansion parts):
* defined as discontinuation due to any of the following:

* Lack of response after at least 4 cycles
* Loss of response (patient must have received therapy for at least 4 cycles)
* Progressive disease
* Adverse events

Note: Patients are eligible if additionally they have failed an ESA

* HMA Naïve group:

* Never received a hypomethylating agent for MDS
* Failed or ceased to respond to ESA(s)
* ESA ineligible; defined as endogenous serum erythropoietin level \> 200 U/L for subjects not previously treated with ESAs
* Red blood cell transfusion dependent defined as ≥ 2 Red blood cells (RBC) units required in the 8 weeks prior to starting in the study. In addition, there should be no 8 consecutive weeks without red blood cell transfusions in the 16 weeks prior to enrolment.
* Life expectancy ≥ 3 months
* Eastern Cooperative Oncology Group (ECOG) performance status Grade 0-2
* Serum bilirubin levels ≤2 x upper limits of normal (ULN)
* Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels ≤2.5 x ULN
* Del 5q patients who have failed or are not eligible for Revlimid
* Creatinine clearance \>30 ml/min calculated by the Cockcroft-Gault formula
* Willingness to comply with the protocol procedures for the duration of the study, including scheduled follow-up visits and examinations
* Negative urine β-human chorionic gonadotropin (β-HCG) pregnancy test for fertile women at screening and confirmed by serum pregnancy test in the 48 hours prior to OPN-305 administration
* If sexually active female, patient must be/have one of the following:
* Post-menopausal defined as the absence of menses for at least one year (serum Follicle-stimulating hormone (FSH) ≥20IU/L can also be measured according to local practice),OR
* Surgically sterile defined as a bilateral tubal ligation at least 6 months prior to administration of study drug, bilateral oophorectomy, or complete hysterectomy, OR
* Using an effective means of contraception that is planned to continue for the duration of treatment and for a further 3 months.
* If sexually active male, patient must: Agree to use an effective means of contraception (per site-specific guidelines) that is planned to continue until 6 months after the last dose of OPN-305.Agree not to donate sperm until 6 months after the last dose of OPN-305

Exclusion Criteria:

* Diagnosis of MDS by bone marrow aspirate of Intermediate-2 and High risk category MDS based on the World Health Organization (WHO) classification using the IPSS (International Prognostic Scoring System)
* Patients with 5q deletion (del) MDS eligible for Revlimid (lenalidomide)
* Hypomethylating agent (HMA) Naïve group:

* Have received a hypomethylating agent for MDS
* Have not failed or ceased to respond to an ESA
* Are not ESA ineligible as defined in inclusion criteria
* Prior history of acute leukemia or AML
* Unable/unwilling to undergo bone marrow sampling
* Prior history of bone marrow transplantation
* Prior malignancy (other than non-invasive malignancy including in situ cervical cancer, Bowen's disease, basal cell cancer of the skin and non-invasive or excised skin squamous cell carcinoma) unless treated with curative intent and without evidence of disease for 3 years before randomization
* Active viral or bacterial infections: this includes any infections that are being actively treated even if the signs and symptoms appear to have resolved. Courses of antibiotics or anti-viral treatment should be completed before the patients is enrolled
* Unstable angina, congestive heart failure \[NYHA (New York Heart Association) \>class II\], uncontrolled hypertension \[diastolic \> 100 mmHg\], uncontrolled cardiac arrhythmia, or recent (within 1 year) myocardial infarction, uncontrolled diabetes mellitus
* Clinical Evidence of Central Nervous System (CNS) disease
* Less than 4 weeks since any therapy for MDS
* Prior history of anaphylaxis to similar products
* History or presence of a medical condition or disease or substance abuse that in the investigator's assessment would place the patient at an unacceptable risk for study participation
* Lactating or pregnant woman