Session: 634. Myeloproliferative Syndromes: Clinical: Poster I
Study Design and Methods: This phase 1, multicenter, dose-escalation, open-label study is evaluating TP-3654 monotherapy in patients with MF who previously failed a JAK inhibitor or who are ineligible to receive ruxolitinib or fedratinib (NCT04176198). Primary objectives are to determine the incidence of dose-limiting toxicities (DLT) at escalated doses of TP-3654 and treatment emergent adverse events. Secondary objectives are to determine QT interval changes, establish the pharmacokinetic profile, and assess preliminary disease activity. Exploratory objectives are pharmacodynamic markers in peripheral blood and bone marrow biopsy samples. Eligible patients have a primary or secondary MF (post-polycythemia vera-MF/post-essential thrombocythemia-MF) based on the World Health Organization diagnostic criteria and intermediate-2 or high-risk primary or secondary MF based on the Dynamic International Prognostic Scoring System; previously failed, or are ineligible to receive, treatment with a JAK inhibitor; grade ≥2 MF, as confirmed by BM biopsy ≤12 weeks prior to screening; have a platelet count >50x109/L, absolute neutrophil count ≥1x109/L, hemoglobin level ≥8 g/L, peripheral blood blast counts <10%, Eastern Cooperative Oncology Group performance status ≤2, life expectancy ≥3 months, and adequate renal and hepatic function; have spleen length ≥5 cm by palpation or spleen volume ≥450 cm3 by computerized tomography/magnetic resonance imaging, and show ≥2 measurable symptoms per the MF Symptom Assessment Form, version 4.0. Patients must not have received prior systemic antineoplastic therapy or any experimental therapy within 14 days or 5 half-lives before TP-3654; had major surgery ≤2 weeks before first study dose; have had splenic irradiation ≤6 months prior to screening; have acute myeloid leukemia or myelodysplastic syndrome; or had prior stem cell transplantation (SCT) or be eligible for allogeneic bone marrow or SCT. Enrollment of approximately 50 patients is planned. Patients will receive oral TP-3654. Dose-escalation will be performed using a Bayesian logistic regression model with escalation with overdose control. Adverse events occurring during the first cycle will be considered in the determination of the maximum tolerated dose (MTD). Dose escalation will continue until identification of the MTD or a suitable recommended phase 2 dose. This study is currently recruiting patients.
Disclosures: Lebedinsky: Sumitomo Dainippon Pharma Oncology, Inc.: Current Employment. Anthony: Exact Sciences: Consultancy; Sumitomo Dainippon Pharma Oncology, Inc.: Current Employment. Mohi: Tolero Pharmaceuticals Inc.: Research Funding. Yang: Sumitomo Dainippon Pharma Oncology, Inc.: Current Employment. Mei: Sumitomo Dainippon Pharma Oncology, Inc.: Current Employment. Braendle: Sumitomo Dainippon Pharma Oncology, Inc.: Current Employment.
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