Novel Oral PIM Kinase Inhibitor Under Study in Resistant Multiple Myeloma
Posted: Thursday, April 22, 2021
The novel oral agent PIM447—a pan-PIM kinase inhibitor—was tolerated in Japanese patients with relapsed or refractory multiple myeloma, according to a recent phase I trial. However, this agent alone had limited antimyeloma activity, so the sponsor terminated the study early to pursue combination therapy research. Masafumi Taniwaki, MD, of Kyoto Prefectural University of Medicine in Japan, and colleagues published their results in the International Journal of Hematology.
“As PIM447 may serve as a promising combination partner in the treatment of patients with multiple myeloma, further dose-finding studies in Japanese patients with multiple myeloma are needed to define an optimal dose for combination regimens,” the authors wrote.
The open-label dose-escalation study included 13 patients with relapsed or refractory multiple myeloma across multiple medical centers in Japan. Patients received PIM477 orally once per day. Seven patients received 250 mg, and six patients received 300 mg.
The overall response rate was 15.4% (2 of 13 patients). Three patients experienced clinical benefit, and nine patients experienced disease control. The sponsor ended the study before the maximum tolerated dose or the recommended dose for expansion could be determined.
All 13 patients had one or more grade 3 or 4 adverse events, most frequently thrombocytopenia (8 of 13 patients) or leukopenia (8 of 13 patients). The most common adverse events that were suspected to be treatment-related were thrombocytopenia (10 patients), anemia (7 patients), and leukopenia (7 patients). There was one dose-limiting toxicity: a grade 3 QTc prolongation in one patient who was receiving the 300 mg dose of PIM447.
Disclosure: The study authors’ disclosures may be found at link.springer.com.