On November 14, 2022 Aptose Biosciences Inc. ("Aptose") (NASDAQ: APTO, TSX: APS), a clinical-stage company developing highly differentiated therapeutics targeting the underlying mechanisms of cancer, reported dosing of the first patient to receive a continuous dosing regimen of the G3 formulation of luxeptinib, a potent, non-covalent oral inhibitor of BTK and FLT3, in the ongoing Phase 1a/b clinical trial in patients with relapsed or refractory (r/r) acute myeloid leukemia (AML) (Press release, Aptose Biosciences, NOV 14, 2022, View Source [SID1234623971]).
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The new G3 formulation thus far has been tested as a single dose in 20 patients from an ongoing Phase 1 clinical program of luxeptinib. Modeling of the pharmacokinetic (PK) properties of G3 predicts steady-state plasma exposure from continuous dosing with 50 mg of G3 (every 12 hours, Q12h) should be comparable to that of 900 mg of the original G1 formulation Q12h, representing a significant improvement in bioavailability with G3. Patients now will receive continuous dosing at the 50mg G3 Q12h dose, with the protocol allowing for further dose escalation of G3 in subsequent patients.
"We’re pleased to incorporate the new G3 formulation of luxeptinib into our clinical trial," said William G. Rice, Ph.D., Chairman, President, and Chief Executive Officer. "Preclinically, Lux is an extraordinary molecule, eradicating tumors with the absence of toxicity, and clinically, one patient administered the original G1 formulation in the AML trial achieved exposures that enabled a complete remission (CR). We are hopeful the G3 formulation will result in greater exposures of luxeptinib and additional responses in this difficult-to-treat patient population."
About Luxeptinib (formerly CG-806)
Luxeptinib is an oral, first-in-class FLT3 and BTK kinase inhibitor in Phase 1 a/b clinical studies for the treatment of myeloid hematologic malignancies. This small molecule demonstrates potent inhibition of wild type and all mutant forms of FLT3 (including internal tandem duplication, or ITD, and mutations of the receptor tyrosine kinase domain and gatekeeper region) and cures animals of AML in the absence of toxicity in murine leukemia models. Likewise, luxeptinib demonstrates potent, non-covalent inhibition of the wild type and Cys481Ser (C481S) mutant forms of the BTK enzyme, as well as other oncogenic kinase pathways operative in B cell malignancies, suggesting luxeptinib may be developed for various B cell malignancy patients that are resistant/refractory/intolerant to covalent or other non-covalent BTK inhibitors. Luxeptinib also inhibits NLRP3 inflammasome function in THP-1 monocytes and bone marrow-derived macrophages, suggesting potential indications in inflammatory conditions.