Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of Mutant Calreticulin Targeted Antibodies in CALR-mutant Myeloproliferative Neoplasms

NCT07849231 | Recruiting Phase 1 FDA Drug

• 1 other identifier: DMRA-MPN-101
• Study Type: interventional
• Target: 250
• Locations: 1 country
• Sites: 4

Brief Summary

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.

Conditions

Myeloproliferative Neoplasms (MPNs)

Keywords

Myeloproliferative Neoplasms; Myelofibrosis; Essential Thrombocythemia; CALR mutation

Outcome Measures

Primary Outcomes (1)

• 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)

  Up to 672 days

Secondary Outcomes (7)

• Evaluate preliminary clinical activity of DMR-001 as a monotherapy in participants with CALR-mutant ET

  Up to 672 days

• Evaluate preliminary clinical activity of DMR-001 as a monotherapy or in combination with ruxolitinib in participants with CALR-mutant MF

  Up to 672 days

• Pharmacokinetics parameter: Cmax of DMR-001 when administered as monotherapy or in combination with ruxolitinib

  Up to 672 days

• Pharmacokinetics parameter: Tmax of DMR-001 when administered as monotherapy or in combination with ruxolitinib

  Up to 672 days

• Pharmacokinetics parameter: AUC(0-t) of DMR-001 when administered as monotherapy or in combination with ruxolitinib

  Up to 672 days

Study Arms (3)

Part 1: DMR-001 monotherapy dose escalation phase.

EXPERIMENTAL

DMR-001 will be administered starting once every 4 weeks as a subcutaneous injection at the protocol defined starting dose and dosing schedule to identify the maximum tolerated dose and/or recommended dose(s) for expansion.

Drug: DMR-001

Part 2: DMR-001 monotherapy dose expansion phase.

EXPERIMENTAL

DMR-001 will be administered starting once every 4 weeks as a subcutaneous injection at the determined recommended dose(s) for expansion based on Part 1.

Drug: DMR-001

Part 3: DMR-001 and ruxolitinib combination dose escalation followed by dose expansion.

EXPERIMENTAL

DMR-001 will be administered starting once every 4 weeks as a subcutaneous injection at the determined dose and regimen, but in combination with an oral tablet of ruxolitinib, a standard of care drug approved therapy for the treatment of MF.

Drug: DMR-001; Drug: Ruxolitinib

Interventions

DMR-001 DRUG

DMR-001 will be administered at protocol defined dose at a frequency of every 4 weeks.

Part 1: DMR-001 monotherapy dose escalation phase.; Part 2: DMR-001 monotherapy dose expansion phase.; Part 3: DMR-001 and ruxolitinib combination dose escalation followed by dose expansion.

Ruxolitinib DRUG

Ruxolitinib will be administered according to Prescribing Information/SmPC.

Also known as: Jakafi, Jakavi

Part 3: DMR-001 and ruxolitinib combination dose escalation followed by dose expansion.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• History of clinically significant or uncontrolled cardiac disease.
• Active HBV, HCV or HIV.
• Known hypersensitivity to DMR-001 or ruxolitinib or any of their components.

Sponsors & Collaborators

• Damora Therapeutics: lead

Study Sites (4)

Site AU08

Liverpool, New South Wales, 2170, Australia

NOT YET RECRUITING

Site AU09

Sydney, New South Wales, 2050, Australia

RECRUITING

Site AU06

Melbourne, Victoria, 2031, Australia

NOT YET RECRUITING

Site AU03

Melbourne, Victoria, 3004, Australia

NOT YET RECRUITING

MeSH Terms

Conditions

Myeloproliferative Disorders; Primary Myelofibrosis; Thrombocythemia, Essential

Interventions

ruxolitinib

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Blood Coagulation Disorders; Thrombocytosis; Blood Platelet Disorders; Hemorrhagic Disorders

Central Study Contacts

Damora Therapeutics Medical Monitor

CONTACT

+1 782-281-9020; ClinicalTrials@Damoratx.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 21, 2026
• First Posted: September 30, 2026
• Study Start: September 1, 2026
• Primary Completion (Estimated): June 1, 2030
• Study Completion (Estimated): June 1, 2030
• Last Updated: September 30, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share

Locations

AU (4)