A Study of JNJ-88549968 for the Treatment of Calreticulin (CALR)-Mutated Myeloproliferative Neoplasms
Key claim: A Phase 1/2 dose-escalation and expansion study is evaluating the safety, recommended phase 2 dose, and optimal dosing schedule of JNJ-88549968 as monotherapy and in combination with ruxolitinib or momelotinib in patients with CALR-mutated ET or MF.
Abstract
The purpose of this study is to characterize safety and to determine the Recommended Phase 2 Dose (RP2D[s]) and optimal dosing schedule(s) of JNJ-88549968 in part 1 (Dose Escalation); to characterize the safety of JNJ- 88549968 at RP2D(s) in part 2 (Cohort Expansion). For U.S. sites: the purpose of this study is to characterize the safety and to determine the RP2D(s) and optimal dosing schedule(s) of JNJ-88549968 in Part 1 and part 1b (Dose Escalation), and to characterize the safety of JNJ-88549968 at the RP2D(s) in Part 2 and part 2b (Cohort Expansion), when given as monotherapy in essential thrombocythemia (ET) or myelofibrosis (MF), and with ruxolitinib or momelotinib in MF only.
Why this matters
JNJ-88549968 represents a shift toward genotype-directed therapy in MPNs by specifically targeting CALR-mutated disease, a molecularly-defined subpopulation that spans both ET (~25–30%) and MF (~25–35%) and has historically shown poorer molecular responses to interferon than JAK2-mutant disease. The trial’s design — monotherapy plus combinations with ruxolitinib or momelotinib — positions a CALR-selective agent as both a standalone option and a backbone-addition strategy, potentially reshaping subtype-specific natural history if disease modification is achieved in the CALR-mutated subset.