On June 12, 2019 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 1/2 study evaluating the investigational agent TP-0903, an AXL receptor tyrosine kinase (RTK) inhibitor, in patients with previously treated chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) (Press release, Tolero Pharmaceuticals, JUN 12, 2019, View Source [SID1234537051]). The open-label, dose-escalation, safety, pharmacokinetics, and pharmacodynamic study will evaluate the dose-limiting toxicities and clinical activity of oral TP-0903 administered in patients with previously treated CLL/SLL, as monotherapy or in combination with ibrutinib.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Although there have been significant advances in the treatment of CLL and SLL in recent years, there remains an area of clinical unmet need for patients who have had disease progression or relapse with available therapies." said David J. Bearss, Ph.D., Chief Executive Officer of Tolero Pharmaceuticals. "The initiation of this study will allow us to learn more about the clinical profile of TP-0903 and the role of AXL receptor tyrosine kinase (RTK) inhibition in patients with previously treated CLL and SLL."

The primary outcome measures of the Phase 1 study are to determine dose-limiting toxicities and the incidence of treatment-emergent adverse events of oral TP-0903 administered once daily for 28 days in patients with previously treated CLL/SLL. Secondary outcome measures of the Phase 1 study include pharmacokinetics. The recommended Phase 2 dose (RP2D) will be determined in Phase 1 of the study. Phase 2 of the study will begin after the completion of Phase 1. The primary outcome measure of Phase 2 will be to determine the objective response rate according to guidelines set forth by the 2018 International Workshop on CLL. Secondary outcome measures of the Phase 2 study include assessment of duration of response and rate of overall survival.

In Phases 1 and 2 of the study, patients will be assigned to one of two defined patient groups. Patients in Group 1, which includes those who are intolerant to or have progressed on B-cell receptor antagonists and/or BCL-2 antagonists, will receive TP-0903 monotherapy. Patients in Group 2, which includes those who have progression of disease on ibrutinib and the treating provider considers continuation of ibrutinib therapy to be in the best interest of the patient, will receive combination therapy of TP-0903 and ibrutinib. Additional information on this trial, including comprehensive inclusion and exclusion criteria, can be accessed at www.ClinicalTrials.gov (NCT03572634).

About TP-0903
TP-0903 is an investigational oral AXL receptor tyrosine kinase (RTK) inhibitor under evaluation in a Phase 1/2 study in patients with CLL/SLL (NCT03572634) and a Phase 1b study in patients with advanced solid tumors (NCT02729298). Tolero is exploring parallel clinical development paths for TP-0903 in both solid and hematologic malignancies.

About AXL Kinase
AXL belongs to the TAM (Tyro3, AXL and Mer) family of receptor tyrosine kinases and is overexpressed in many human cancers.1 It plays a key role in tumor cell proliferation, survival, metastasis, cellular adhesion and avoidance of the immune response. The overexpression of AXL is associated with a poor patient prognosis and drug resistance.2