Phase Ib, open-label study of add on therapy with CK0804 in participants with myelofibrosis, with suboptimal response to ruxolitinib

TPS7087 Background: Drugs targeting JAK2 inhibition including ruxolitinib have led to significant improvement in quality of life and survival of myelofibrosis (MF) patients, however almost 30% have suboptimal response and disease remains incurable. Novel therapies are urgently needed. In addition to mutation-driven stem cell-derived clonal myeloproliferation, recent data support role of reactive cytokine- and chemokine-driven inflammatory fibrosis that contribute to MF pathogenesis, specifically, abnormal CXCR4/CXCL12 axis can drive disease progression and extramedullary hematopoeisis. Targeting bone marrow inflammation is emerging as potential therapeutic strategy for MF. Adoptive therapy with allogeneic, cord blood (CB) derived Regulatory T cells (Tregs) have shown to be safe in bone marrow failure patients. CXCR4 enriched CB Tregs (CK0804) show faster egress across transwell membrane in response to SDF1α and preferential homing to bone marrow, in vivo. We hypothesize that multiple infusions of CK0804 may decrease inflammation and improve clinical outcomes in MF. Methods: Single arm study consisting of safety run-in of 9 participants followed by expansion cohort of additional 15 participants using 3+3+3 study design. MF patients receiving ruxolitinib therapy > 3 months prior to enrollment with stable dose for at least 8 weeks prior to Day 1, unlikely to benefit from further ruxolitinib monotherapy in opinion of investigator would be eligible. Each participant will receive single infusion of CK0804 at fixed dose of 100 million Treg cells administered every 28 days. Participants will continue their ruxolitinib therapy. Participants with no treatment limiting toxicity (TLT) after 28 days or those with toxicity with clear alternative explanation (e.g. disease progression) or transient (≤72 hrs) abnormal laboratory values without associated clinically significant signs or symptoms based on investigator determination will receive up to six 28-day treatment cycles AND 6 months of follow up after last infusion of CK0804. Primary Objective: Determine safety and tolerability of CK0804 as add-on therapy in MF, with suboptimal response to ruxolitinib. Primary endpoint: Safety, tolerability and TLTs of CK0804 as assessed by incidence and severity of AE and SAEs determined by NCI CTCAE Version 5.0. Secondary Objective: Determine efficacy of CK0804 as add-on therapy in MF, with suboptimal response to ruxolitinib. Secondary endpoint: Assessment of overall response rate and its duration, using modified International Working Group Myeloproliferative Neoplasm Research and Treatment and European Leukemia Net consensus report; Rate of anemia response and Rate of spleen response by imaging at and after 24 weeks; Symptom burden assessed using Myeloproliferative Neoplasms Symptom Assessment Form Total Symptom Score scale. Safety data from cohort 1 will be presented. Clinical trial information: NCT05423691 .