On October 23, 2018 Deciphera Pharmaceuticals, Inc. (NASDAQ:DCPH), a clinical-stage biopharmaceutical company focused on addressing key mechanisms of tumor drug resistance, reported that it has initiated an open-label, multicenter, Phase 1b/2 study of rebastinib in combination with paclitaxel to assess safety, tolerability, pharmacokinetics and efficacy in patients with advanced or metastatic solid tumors (Press release, Deciphera Pharmaceuticals, OCT 23, 2018, View Source [SID1234530064]).
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"We are excited to initiate this Phase 1b/2 clinical trial of rebastinib, our small molecule switch control inhibitor of TIE2," said Michael D. Taylor, Ph.D., Deciphera’s President and Chief Executive Officer. "In preclinical testing rebastinib has shown activity as a single agent and when combined with paclitaxel, we observed synergistic reductions in circulating tumor cells and ablating distant metastases. As a result, we believe rebastinib has the potential to be an important new therapy for cancer patients when combined with chemotherapy. In addition to the Phase 1b/2 clinical trial with paclitaxel, we intend to initiate a second Phase 1b/2 clinical trial of rebastinib in combination with carboplatin in the coming months."
In this two-part Phase 1b/2 clinical trial, rebastinib will be evaluated for the treatment of patients with advanced or metastatic solid tumors in combination with paclitaxel. Part 1 is designed to evaluate the safety, tolerability and pharmacokinetics of 50 mg and 100 mg rebastinib twice daily (BID) when administered in combination with paclitaxel, and to determine the recommended phase 2 dose (RP2D) of rebastinib in combination with paclitaxel, in patients with advanced or metastatic solid tumors that are refractory to standard therapies. In part 2, the safety, tolerability and efficacy of the RP2D of rebastinib in combination with weekly paclitaxel will be assessed across multiple cohorts, including: breast cancer, ovarian cancer, and endometrial cancer. This trial will enroll up to 36 evaluable patients in part 1 and up to 132 evaluable patients in part 2. For more information about the clinical trial design please visit www.clinicaltrials.gov (NCT03601897).
"There is an increasing understanding of the mechanisms by which tumors co-opt the surrounding microenvironment to grow, survive and become more invasive. TIE2 kinase is involved in multiple mechanisms favoring a pro-tumoral microenvironment, including the regulation of a population of immunosuppressive macrophages, promotion of tumor angiogenesis, and participation in perivascular pumps that lead to tumor cell intravasation and distal metastasis," said Oliver Rosen, M.D., Chief Medical Officer at Deciphera. "Certain of these macrophages express TIE2 and we believe selective inhibition of this kinase with rebastinib in combination with paclitaxel is a promising approach to treating these patients."
About Rebastinib
Rebastinib is an investigational, orally administered, potent and selective inhibitor of the TIE2 kinase, the receptor for angiopoietins, an important family of vascular growth factors in the tumor microenvironment that also activate pro-tumoral TIE2 expressing macrophages. In a Phase 1 clinical trial, biomarker data have demonstrated rebastinib-induced increases in the TIE2 ligand angiopoietin 2, secondary to TIE2 inhibition. Rebastinib is currently being evaluated in a Phase 1b/2 clinical trial in combination with paclitaxel (NCT03601897) and an investigator sponsored Phase 1b trial in patients with metastatic breast cancer in combination with paclitaxel or eribulin (NCT02824575).