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.
Who is it for? You may be eligible to join this study if you are aged 18 years and over have been diagnosed with Essential Thrombocythemia and either a Morphologically confirmed diagnosis of Myeloproliferative Neoplasms (MPN) or Myelodysplastic/Myeloproliferative Neoplasms (MDS/MPN).
Study details:
Participants in this study will receive JBI-802 administered orally daily for a 28 day treatment cycle for up to 2-years as long as the participant experiences clinical benefit in the opinion of the Investigator and shows no signs or symptoms of unequivocal progression of disease, unacceptable toxicity, or other reasons for study discontinuation. The starting dose of the study drug is 5 mg/day, a total dose of 35 mg. Dose escalation will occur as per the 3+3 design after an internal Safety Review Committee (SRC) review of each dose stage. Dose expansion to other subtypes of MPN and MDS/MPN will occur after Recommended Phase 2 Dose is determined from the dose escalation phase. Eligibility/Screening for this study will occur within 21 days prior to starting treatment. If the study is suitable for you, you will enter the treatment period. The dose level selected for evaluation in Phase 2 will only be selected if it was safe and well tolerated during Phase 1. The treatment cycles will continue until you wish to stop, or you do not tolerate JBI-802 treatment,
Some of the study procedures that include during your treatment period are :Medical, surgical, and cancer history, Height and weight, Physical examination, Vital signs, Eastern Cooperative Oncology Group (ECOG) evaluation, Electrocardiogram, Myeloproliferative neoplasm symptom assessment questionnaire,CT/MRI scan, Bone marrow biopsy, medication usage, Side effects assessment, blood and urine Sampling , liver and thyroid function tests, haematology and coagulation tests, Participants will be followed-up at the start and end of each 28-day cycle to assess safety and tolerability Blood samples will be collected to assess safety and tolerability during the study.
After the end of study, subjects will be treated in accordance with local practice. Compassionate use of JBI-802 may be allowed in subjects after study completion, based on the Investigator's judgment in consultation with the Sponsor and on a case-by-case basis. Compassionate use will be controlled by a separate protocol or process as defined by the local regulatory authorities. Continuation of study therapy beyond 2 years may be approved by the Sponsor based on the safety profile and will be contingent on the continued availability of product.
Subject with diagnosis of Essential Thrombocythemia (ET) per World Health Organization (WHO) diagnostic criteria for myeloproliferative neoplasms .
Subject requires treatment in order to lower platelet count based on subject age over 60 or history of thrombosis.
Subject with Morphologically confirmed diagnosis of MDS/MPN neoplasms, excluding Juvenile Myelomonocytic Leukaemia (JMML), CMML and aCML (Atypical Chronic 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, (unclassifiable (MDS/MPN-UC) and MDS/MPN-RS-T).
1. Subject who is treated with systemic anticancer therapy or biological therapy or an investigational agent within 2 weeks or 5 half-lives, whichever is shorter, prior to start of study drug treatment.
For MF subject who come off JAK2 antagonists or hydroxyurea, shorter washout is permitted as these subject progress quickly after treatment discontinuation and remain eligible (steroids must be stop at least 7 day before start of study drug treatment)
Subject who is in need of immediate cytoreduction should be excluded 2. Subject who has undergone autologous/allogeneic Haematopoietic Stem Cell Transplantation (HSCT) therapy within 60 days of the first dose of study drug, or subject on immunosuppressive therapy post-HSCT at the time of screening, or currently with clinically significant Graft-Versus- Host Disease (GVHD) as per treating physician (subjects in relapse after allogeneic transplantation must be off treatment with systemic immunosuppressive agents for at least 4 weeks prior to screening.
Patient with previous cancers can be included to the study provided they are in remission at the time of screening and enrolment.
Sequential
JBI-802
DrugCoREST inhibitor dual targeting LSD1 and HDAC6
Dose Escalation - Incidence of Dose-Limiting Toxicities (DLTs)
Number of participants with dose-limiting toxicity (DLT) events during the DLT monitoring period. DLTs are defined per protocol criteria and graded using NCI CTCAE Version 5.0. Units: Number of participants
Dose Expansion - Overall Response Rate (ORR)
Percentage of participants with best overall response of complete response or partial response according to MPN IWG-MRT or MDS/MPN IWG criteria. Units: Percentage of participants
Dose Expansion - Complete Remission (CR) Rate
Percentage of participants achieving complete remission per IWG criteria. Units: Percentage of participants
Dose Expansion - Progression-Free Survival (PFS)
Time from first dose to disease progression or death from any cause. Units: Months
Dose Escalation - Incidence of Treatment-Emergent Adverse Events (TEAEs)
Number of participants with treatment-emergent adverse events, classified by system organ class and severity according to NCI CTCAE v5.0. Units: Number of participants
Maximum Plasma Concentration (Cmax) of JBI-802
Maximum observed plasma concentration of JBI-802 following dosing. Units: ng/mL
Area Under the Plasma Concentration-Time Curve (AUC0-t) of JBI-802
Area under the plasma concentration-time curve from time 0 to last measurable concentration.
Time to Maximum Plasma Concentration (Tmax) of JBI-802
Time to reach maximum plasma concentration.
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