A Phase Ib, Open-Label Study of Add on Therapy with CK0804 in Participants with Myelofibrosis and Suboptimal Response to Ruxolitinib

• Published in: Blood 2023-11, Vol.142 (Supplement 1), p.1813-1813
• Main Authors: Masarova, Lucia, Huang, Meixian, Bledsoe, Sharon, Pemmaraju, Naveen, Kadia, Tapan M., Bose, Prithviraj, Ishizawa, Jo, Montalban-Bravo, Guillermo, Lyu, Mi-Ae, Zeng, Ke, Sadeghi, Tara, Asatiani, Ekatherine, Parmar, Simrit, Flowers, Christopher R., Kantarjian, Hagop M.
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2023-188051

Background: JAK2 inhibitor ruxolitinib leads to improvements in symptom burden and spleen volume in patients with myelofibrosis (MF), but suboptimal response represents a major unmet clinical need. Deregulated inflammatory pathways including CXCR4/CXCR12 axis might limit the therapeutic efficacy of ruxolitinib and contribute to disease progression ( Miwa et al. Pathology. 2013), where agents targeting bone marrow (BM) inflammation could be promising. Adoptive therapy with allogeneic, cord blood-derived regulatory T cells (Tregs) (CK0801- HLA 3/ 6 match, fresh infusion) showed safety and early clinical signal in MF ( Kadia et al., Blood. 2020). In preclinical studies, the next generation product, CK0804, consisting of CXCR4 enriched Tregs [CK0804] shows preferential homing to BM and decrease inflammatory cytokines including TGFα, TNFβ, IL-13 and TGFβ when compared to unmanipulated control Treg cells ( Huang et al., Cytotherapy, 2023). Methods:This phase Ib study evaluates the safety and activity of CK0804 (non-HLA matched, Cryopreserved, Multi-Dose) Treg therapy in patients with suboptimal response to ruxolitinib. The study design consists of a safety run-in phase of 9 patients followed by an expansion of additional 15 patients. Participants will continue ruxolitinib and receive infusion of CK0804 at a fixed dose of 100 million Treg cells every 28 days up to 6 cycles. All patients are monitored for 6 months following the last infusion. 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 includes overall response per IWG-MRT criteria at 24 weeks. Exploratory objectives evaluate pharmacodynamics, pharmacokinetics, markers of immunogenicity and inflammation. Results: As of 1 st of July 2023, 5 patients were enrolled and treated with a median age of 68 years [range 60-78], 60% males (table). Median number of previous MF therapies was 1.5 (range 1-4), median duration of previous ruxolitinib therapy was 38 months (range, 10-132). At enrollment, all patients were symptomatic with median MPN-SAF TSS of 35 (range, 24-40), 3 patients had worsening splenomegaly and 3 patients were transfusion dependent. All patients had grade 2+ reticulin marrow fibrosis with most also having significant collagen or osteosclerosis, 40% were JAK2 V617F mutated and 80% had additional co-mutations (table). Two (2) patients received all six (