A phase Ib, open-label study of add-on therapy with CK0804 in participants with myelofibrosis and suboptimal response to ruxolitinib.
Authors: Masarova Lucia , Huang Meixian , Goel Swati , Bledsoe Sharon , Pemmaraju Naveen , Kadia Tapan M. , Bose Prithviraj , Ishizawa Jo , Bravo Guillermo Montalban , Lyu Mi-Ae , Sadeghi Tara , Assatiani Ekaterina , Parmar Simrit , Flowers Christopher , Kantarjian Hagop M. 
Published: June 2024

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Background: Suboptimal response to JAK2 inhibitor ruxolitinib in patients with myelofibrosis (MF) remains a major unmet medical need. Deregulated inflammatory pathways including CXCR4/CXCR12 axis might limit the therapeutic efficacy of ruxolitinib and contribute to disease progression. In preclinical studies, cord blood-derived, CXCR4 enriched T regulatory cells [CK0804; T-regs] showed ability to suppress inflammatory cytokines playing major role in MF (Huang et al., Cytotherapy, 2023). Methods: This phase Ib study evaluates the safety and activity of up to 6 doses of CK0804 (non-HLA matched, Cryopreserved) T-regs therapy, fixed dose of 100 million cells, added every 28 days to ruxolitinib. Patients with MF on ruxolitinib for ≥12 weeks and stable dose for ≥8 weeks, who have palpable splenomegaly, symptoms, or grade 2 cytopenia are eligible. Primary objective is safety, secondary objective is overall response per IWG-MRT criteria at 24 weeks. Present analysis includes cohort of initial run-in safety phase. Results: Nine patients of median age 68 years (range, 55-84) were enrolled, 44% were males. Median blood counts [range] showed while blood cells 10.6 [3.1-70.4] x10^9/L, hemoglobin 8.8 [7.8-11.5] g/dL, platelets 177 [148-311] x10^9/L. Three patients were transfusion dependent. Median spleen volume was 1449 cubic centimeters (176-5609), 7 patients (78%) had clinically worsening splenomegaly. Median symptoms score (MPN-SAF TSS) was 23 (20-40). Six (67%) had diploid karyotype, 5 (56%) had JAK2 mutation and 8 (89%) had additional no-driver mutations. Median duration of prior ruxolitinib was 35 months (range, 10-132), all patients were on ≥ 10 mg twice daily dose with no dose change throughout the study. Four patients received all six doses of CK0804, three patients have ongoing treatments. One patient experienced infusion reaction to second dose of CK0804 likely due to the excipient dimethylsulfoxide and withdrew consent. One patient died of unrelated cause prior to the infusion 6. There were no nonhematologic or hematologic adverse events. Two transfusion dependent patients who were evaluable for response had decreased monthly need for transfusions by the end of the sixth cycle: 4 to 2.8 units and 1.2 to 0.8 units, respectively. All patients noticed symptoms improvement; median best decline in MPN-SAF TSS was -38% (range, -20% to -71%); with ≥ 50% reduction in 3 patients. One patient achieved ≥ 35% spleen volume reduction at week 12. Longitudinal analysis of markers of inflammation is in progress and will be presented at the conference. Conclusions: This preliminary analysis of run-in phase of study evaluating CXCR4 enriched T regs cell therapy as addition to ruxolitinib shows initial safety with no myelosuppressive adverse events and promising clinical activity. Active enrollment of participants to the expansion cohort is ongoing. Clinical trial information: NCT05423691 .