Phase 1/ Phase 2 Study to Assess Safety and Efficacy of Orally Administered JBI-802 in Subjects with Myeloproliferative Neoplasms (MPN) and Myelodysplastic/Myeloproliferative Neoplasms (MDS/MPN) with Thrombocytosis.

ACTRN 12624000478516

Brief Summary

This study aims to assess the safety and efficacy of orally administered JBI-802 in subjects with Myeloproliferative Neoplasms (MPN) and Myelodysplastic/ Myeloproliferative Neoplasms (MDS/MPN) with Thrombocytosis.

Intervention/Treatment

• Drug: JBI-802

Inclusion Criteria

Male or female subjects aged greater than 18 years at the time of screeningtesting for cancer or conditions that can lead to cancer before symptoms appear, also known as cancer screening visit.

For Dosethe amount of medication taken Escalation Phase: Subjects diagnosed with any one of the following:

• Subject with diagnosisthe process of identifying a disease based on signs and symptoms, patient history and medical test results of Essential Thrombocythemia (ET) per World Health Organization (WHO) diagnostic criteria for myeloproliferative neoplasms that is relapsed and/or refractory or intolerant to standard of care and that, in the opinion of the Investigator, subjects who have no available therapies known to provide clinical benefits.
• Subject requires treatment in order to lower platelet count based on subject age over 60 or history of thrombosis.
• Subject with diagnosis of Polycythemia Vera (PV) with Thrombocythemia per WHO diagnostic criteria that is relapsed and/or refractory or intolerant to standard of care and that, in the opinion of the Investigator, subjects who have no available therapies known to provide clinical benefits.
• Subject with morphologically confirmed diagnosis of pre-fibrotic myelofibrosis (MF) with thrombocythemia in accordance with the WHO 2016 revised criteria, that is relapsed, intolerant, and/or refractory and that, in the opinion of the Investigator, subjects who have no available therapies known to provide clinical benefits.
• Subject with Morphologically confirmed diagnosis of MDS/MPN neoplasms, excluding Juvenile Myelomonocytic Leukaemiacancer of blood and/or blood forming tissues (JMML), CMML and aCML (Atypical Chronica long-lasting disease that changes slowly over time Myeloid Leukaemia), in accordance with WHO 2016 revised criteria, that is relapsed and/or refractory or intolerant to standard of care and that, in the opinion of the Investigator, subjects who have no available therapies known to provide clinical benefits.
• Subject with Myelodysplastic/myeloproliferative neoplasm.

For Dose Expansion Phase
Subjects diagnosed with any one of the following:

• Subject with diagnosis of Essential Thrombocythemia (ET) per WHO diagnostic criteria for myeloproliferative neoplasms which requires treatment in order to lower platelet count based on subject age over 60 or history of thrombosis.
• Subject with diagnosis of Polycythemia Vera (PV) per WHO diagnostic criteria that is relapsed and/or refractory or intolerant to standard of care and that, in the opinion of the Investigator,subjects who have no available therapies known to provide clinical benefits.
• Subject with morphologically confirmed diagnosis of pre-fibrotic myelofibrosis (MF) subject in accordance with the WHO 2016 revised criteria, that is relapsed, intolerant, and/or refractory and that, in the opinion of the Investigator, subjects who have no available therapies known to provide clinical benefits.

1. MDS/MPN (MDS/MPN-RS-T, MDS/MPN unclassifiable and CMML subjects providing the marrow blast count is less than or equal to 5%.).
2. Subject must have disease that failed at least one standard therapy or being intolerant to standard of care.
3. Subject must have discontinued immediate prior therapy at least 1 week prior to study drug administration. However, interferon discontinuation prior to study drug administration will be determined by the half-life of the specific variant/or 4 weeks at the discretion of the Investigator.
4. Subject with screening laboratory values:
   • Haemoglobin (Hb) greater or equal to 9 g/dL, if subject is transfused to meet this criterion, transfusion must be completed greater or equal to 14 days prior to first dose.
   • Absolute neutrophil count greater or equal to 1.5 × 10^9/L.
   • Absolute neutrophil count greater or equal to 1.0 × 10^9/L, if significant marrow infiltration.
   • Platelet count greater or equal to 450 × 10^9/L for dose finding.
   • Platelet count greater or equal to 150 × 10^9/L for expansion cohort at RP2D, if subject is transfused to meet this criterion, transfusion must be completed greater or equal to 14 days prior to first dose.
   • Total bilirubin less than or equal to 1.5 × ULN. Subjects with Gilbert’s syndrome may be enrolled with up to 3.0 × ULN.
   • Aspartate transaminase (AST) and Alanine transaminase (ALT) less than or equal to 2.5 × ULN.
   • Calculated creatinine clearance (CrCL) greater or equal to 30 mL/min (Cockcroft-Gault formula).
   • Prothrombin Time (PT) or Activated Partial Thromboplastin Time (aPTT) less than or equal to 1.5 × ULN, if subject is not anticoagulated (Note: If subject is on anticoagulants, the subject must be on a stable dose for at least 2 weeks prior to screening).
5. Subject with resolution of any clinically significant toxic effects of prior therapy to Gradea description of how abnormal cancer cells and tissue look under a microscope when compared to healthy cells 0 or 1 according to the NCI CTCAE, Version 5.0 (exception of alopeciathe partial or complete absence of hair from areas of the body where it normally grows; baldness and Grade 2 peripheral neuropathy, chronic Grade 2 endocrinopathies as a result of prior immunotherapya treatment that uses a person's immune system to fight cancer).
6. Subject with Eastern Cooperative Oncologythe study, diagnosis and treatment of cancer Group (ECOG) performance status of less than or equal to 2.
7. Subject able to swallow oral medication.
8. A subject who is willing and able to give informed consenta process in which a patient receives detailed information about a procedure or treatment, including its potential risks, benefits, and alternatives. The patient then has the opportunity to understand the information and voluntarily agree to the procedure or treatment. and comply with protocol requirements for the duration of the study.
9. Subject who is willing to undergo bone marrowsoft, spongy tissue found in bones that makes blood cells biopsyremoval of a section of tissue to analyse for cancer cells with aspiration and tissuea group of cells that work together to perform a function collection for disease assessment and correlative studies during screening and periodically throughout the study.
10. Subject with willingness to use contraception by a method that is deemed effective by the Investigator by both males and female of childbearing potential (post-menopausal women must have been amenorrhoeal for at least 12 months to be considered of non-childbearing potential (i.e. surgically sterilised [hysterectomycomplete or partial removal of the uterus, bilateralaffecting both sides salpingectomyremoval of one (unilateral) or both (bilateral) fallopian tubes, bilateral oophorectomyremoval of one (unilateral) or both (bilateral) ovaries at least 6 weeks before the screening visit] or postmenopausal [where postmenopausal is defined as no menses for 12 months without an alternative medical cause and a follicle-stimulating hormonea chemical substance produced by glands in the endocrine system that regulates various functions in the body [FSH] level consistent with postmenopausal status, per local laboratory guidelines]) and their partners throughout the treatment period and for at least 3 months following the last dose of study drug.