Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of Mutant Calreticulin Targeted Antibodies in CALR-mutant Myeloproliferative Neoplasms
Key claim: DMR-001, a mutant calreticulin-targeted antibody, is being evaluated in a Phase 1/1b trial for safety, PK, immunogenicity, and preliminary efficacy as monotherapy in CALR-mutant ET and MF and combined with ruxolitinib in CALR-mutant MF.
Abstract
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.
Why this matters
DMR-001 adds a third mutant-CALR-targeted antibody program alongside INCA033989 and JNJ-88549968, consolidating mutant-CALR neoepitope targeting as a maturing therapeutic class rather than a single-sponsor bet. The parallel enrollment of CALR-mutant ET and CALR-mutant MF (with a ruxolitinib combination arm in MF) reinforces that this mechanism is being pursued across subtypes defined by driver genotype rather than clinical phenotype, with implications for the ~25–30% CALR-mutant ET and ~25–35% CALR-mutant PMF/secondary MF populations where disease-modifying options remain limited.