On July 25, 2018 Tolero Pharmaceuticals, Inc., a clinical-stage company focused on developing novel therapeutics for hematological and oncological diseases, reported that the first patient has been dosed in a Phase 1 study evaluating investigational agent TP-0184, an activin A receptor type 1 (ACVR1) inhibitor, in patients with advanced solid tumors (Press release, Tolero Pharmaceuticals, JUL 25, 2018, View Source [SID1234527870]). The Phase 1, open-label, dose-escalation study will evaluate the safety, pharmacokinetics, and pharmacodynamics of TP-0184 administered orally daily for the first 21 days of a 28-day cycle across a range of doses.
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"The initiation of this study of TP-0184 represents an important milestone for Tolero Pharmaceuticals, as it marks the second investigational agent from our development program to enter the clinical research stage this year,"said David J. Bearss, Ph.D., Chief Executive Officer of Tolero Pharmaceuticals, Inc. "We look forward to understanding more about the profile of TP-0184 and its role in inhibiting ACVR1, which is mutated in approximately 1-4 percent of solid tumors and 32 percent of diffuse intrinsic pontine gliomas (DIPGs), an aggressive form of pediatric brain cancer."
The primary objective of the Phase 1 study is to determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of TP-0184 orally administered daily for 21 days, over a range of doses in patients with advanced solid tumors. Secondary objectives in the study are to evaluate the pharmacokinetics and pharmacodynamics of TP-0184, observe patients for any evidence of antitumor activity of TP-0184 by objective radiographic assessment, and establish the recommended Phase 2 dose for future studies with TP-0184. The trial is being conducted at sites in the United States. Additional information on this trial, including comprehensive inclusion and exclusion criteria, can be accessed at www.ClinicalTrials.gov (NCT03429218).
About TP-0184
TP-0184 is small molecule inhibitor of ACVR1, an activin A receptor type 1 (ACVR1) inhibitor, which is involved in the transforming growth factor beta (TGFβ) signaling pathway. ACVR1, also known as activin receptor-like kinase 2 (ALK2), is mutated in multiple types of cancers, including diffuse intrinsic pontine glioma (DIPG), a malignancy with high morbidity and mortality affecting the pediatric population.1,2,3 ACVR1 mutations are present in approximately 1-4 percent of solid tumors and, more commonly, in 32 percent of diffuse intrinsic pontine gliomas (DIPGs), a brain cancer with high morbidity and mortality afflicting the pediatric population.4,5 There is currently no approved therapy for the treatment of DIPG. ACVR1 is also involved in regulation of iron hemostasis, through stabilization of hepcidin and reduction of bioavailable iron, which is associated with anemia of chronic inflammation.4 TP-0184 is currently being evaluated in a Phase 1 clinical trial in advanced solid tumors (NCT03429218).