This is a multi-center, open-label, Phase 1/1b study designed to evaluate the safety, pharmacokinetics, immunogenicity, and preliminary efficacy of DMR-001 monotherapy in adult participants with CALR-mutated essential thrombocythemia (ET) and myelofibrosis (MF), and of DMR-001 in combination with ruxolitinib in participants with CALR-mutant MF.
Signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF and the protocol.
Diagnosis/confirmation of ET or MF as defined in the protocol.
Documented CALR exon-9 mutation.
Willingness to undergo bone marrow biopsy and aspiration per the Schedule of Assessments.
Presence of any malignancy unless participant has been disease free for at least 2 years.
History of major bleeding or thrombosis within the last 3 months prior to study enrollment.
Prior hematopoietic stem cell transplantation or donor leukocyte infusion, or such transplantation or infusion is planned.
Participants with laboratory values exceeding protocol defined thresholds.
Sequential
DMR-001
DrugDMR-001 will be administered at protocol defined dose at a frequency of every 4 weeks.
Ruxolitinib
DrugRuxolitinib will be administered according to Prescribing Information/SmPC.
To evaluate the safety and tolerability of DMR-001 & determine the MTD, RDE(s), and/or recommended Phase 2 dose(s) in participants with CALR-mutant MPNs, when administered as monotherapy or in combination with ruxolitinib
Incidence and severity of AEs and SAEs, including DLTs and AEs resulting in dose modification (interruption, reduction, or discontinuation)
Evaluate preliminary clinical activity of DMR-001 as a monotherapy in participants with CALR-mutant ET
Objective response rate based on MPN specific response criteria
Evaluate preliminary clinical activity of DMR-001 as a monotherapy or in combination with ruxolitinib in participants with CALR-mutant MF
Established by looking at overall response rate based on MPN specific response criteria, protocol defined spleen volume reduction and protocol defined anemia response.
Pharmacokinetics parameter: Cmax of DMR-001 when administered as monotherapy or in combination with ruxolitinib
Maximum observed plasma concentration of DMR-001 monotherapy or DMR-001 in combination with ruxolitinib
Pharmacokinetics parameter: Tmax of DMR-001 when administered as monotherapy or in combination with ruxolitinib
Time to reach the maximum concentration of DMR-001 monotherapy or DMR-001 in combination with ruxolitinib
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