2019 ASCO Annual Meeting!
Session: Hematologic Malignancies—Leukemia, Myelodysplastic Syndromes, and Allotransplant
Type: Poster Session
Time: Monday June 3, 8:00 AM to 11:00 AM
Location: Hall A
CLI24-001: First-in-human study of SEL24/MEN1703, an oral dual PIM/FLT3 kinase inhibitor, in patients with acute myeloid leukemia.
Hematologic Malignancies—Leukemia, Myelodysplastic Syndromes, and Allotransplant
2019 ASCO Annual Meeting
Poster Board Number:
Poster Session (Board #436b)
J Clin Oncol 37, 2019 (suppl; abstr TPS7062)
Author(s): Farhad Ravandi, Stephen Anthony Strickland, Scott R. Solomon, Aziz Nazha, Roland B. Walter, Ilaria Valimberti, Alessia Tagliavini, Caterina Fiesoli, Monica Binaschi, Krzysztof Brzozka, Simone Baldini, Steffen Heeger, Andrea Ugo Pellacani; The University of Texas, MD Anderson Cancer Center, Houston, TX; Vanderbilt University Ingram Cancer Center, Nashville, TN; The Leukemia Program at Northside Hospital Cancer Center Institute, Atlanta, GA; Leukemia Program, Department of Hematology and Medical Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA; Menarini Ricerche S.p.A., Florence, Italy; Menarini Ricerche SpA, Pomezia, Italy; Selvita S.A., Krakow, Poland; Menarini Ricerche, Firenze, Italy; Menarini Ricerche SpA, Firenze, Italy
Background: FLT3-ITD is one of the most common genetic lesions in acute myeloid leukemia (AML). PIM kinases are oncogenic FLT3-ITD targets expressed in AML cells and increased PIM kinase expression is found in relapse samples from AML patients treated with FLT3 inhibitors. In addition, inhibition of PIM kinases restores sensitivity to FLT3 inhibitors and dual FLT3/PIM inhibition eradicates FLT3-ITD+ cells including primary AML cells. SEL24/MEN1703, a potent PIM/FLT3 dual inhibitor, demonstrates a significantly broader spectrum of activity in AML cell lines and primary AML blasts, irrespective of FLT3 status, compared to monotherapy with either FLT3 or PIM inhibitors such as quizartinib or AZD1208. Methods: CLI24-001 is a First in Human, open label, non-randomized, multi-center, Phase I/II dose-escalation and cohort expansion study of SEL24/MEN1703 in AML patients (excluding APL) not suitable for chemotherapy. SEL24/MEN1703 is given orally, QD, for 14 days in a 21-day cycle with cycles repeated until disease progression or unacceptable toxicity. Dose escalation follows a 3+3 design to identify the recommended phase 2 dose (RP2D). In the phase 2 part/cohort expansion, subjects will receive SEL24/MEN1703 at the RP2D, to further investigate the safety profile and signs of antileukemic activity. In both study parts, patients are eligible regardless of mutational status and/or prior exposure to FLT3 inhibitors; prior treatment with PIM inhibitors is not allowed. Main inclusion criteria comprise a white blood count (WBC) of ≤30 x 109/L (hydroxyurea/leukoapheresis permitted to lower WBC). Key secondary objectives include pharmacokinetics (PK) and single agent efficacy. The study is enrolling at 5 US sites and will be extended, both in US and EU, in the cohort expansion part. This is the first trial testing a dual PIM/FLT3 inhibitor with the potential to be active in AML regardless of FLT3 status andwith a potential to overcome FLT3 inhibitor resistance. (Sci Adv. 2015;1:e1500221; Oncotarget. 2018 Mar 30;9(24):16917-16931) Clinical trial information: NCT03008187