A phase I, dose-escalation study of oral PIM447 in Japanese patients with relapsed and/or refractory multiple myeloma

• Published in: International journal of hematology Vol. 113; no. 6; pp. 797 - 806
• Main Authors: Iida, Shinsuke, Sunami, Kazutaka, Minami, Hironobu, Hatake, Kiyohiko, Sekiguchi, Risa, Natsume, Kazuto, Ishikawa, Norifumi, Rinne, Mikael, Taniwaki, Masafumi
• Format: Journal Article
• Language: English
• Published: Singapore Springer Singapore 01.06.2021; Springer Nature B.V
• Subjects: Adverse events; Anemia; Disease control; Dosage; Enzyme inhibitors; Hematology; Kinases; Leukemia; Leukopenia; Medicine; Medicine & Public Health; Multiple myeloma; Oncology; Original Article; Patients; Prolongation; Thrombocytopenia; Toxicity; Clinical trials; Phase I; PIM kinase; Multiple myeloma; PIM447
• ISSN: 0925-5710; 1865-3774
• DOI: 10.1007/s12185-021-03096-9

PIM447, a pan-proviral integration site for Moloney leukemia (PIM) kinase inhibitor, has shown preclinical activity in multiple myeloma (MM). This phase I, open-label, multicenter, dose-escalation study aimed to determine the maximum tolerated dose (MTD) and recommended dose for expansion (RDE) of PIM447 in Japanese patients with relapsed and/or refractory (R/R) MM. The study included 13 patients (250 mg once daily (QD), [ n  = 7]; 300 mg QD, [ n  = 6]). The sole dose-limiting toxicity observed was grade 3 QTc prolongation in one patient from the 300 mg group, and the MTD and RDE was not determined. The most common suspected PIM447-related adverse events (AEs) included thrombocytopenia (76.9%), anemia (53.8%), and leukopenia (53.8%). All patients experienced at least one grade 3 or 4 AE, most frequently thrombocytopenia or leukopenia (61.5% each). The overall response rate was 15.4%, disease control rate 69.2%, clinical benefit rate 23.1%, and two patients had a partial response (one in each dose group). Two patients treated with 250 mg QD had a progression-free survival > 6 months. PIM447 250 mg or 300 mg QD was tolerated in Japanese patients with R/R MM. Further studies are required to evaluate clinical outcomes of PIM447 in combination with other drugs for the treatment of MM. Trial registration : clinicaltrials.gov: (NCT02160951).