Deciphera Pharmaceuticals has started a Phase Ib/II trial to evaluate the safety, tolerability, pharmacokinetics and efficacy of rebastinib in combination with paclitaxel in patients with advanced or metastatic solid tumours.
The open-label, multicentre, randomised trial comprises two parts and aims to include 100 subjects.
Part one of the trial will investigate the safety, tolerability and pharmacokinetics of 50mg and 100mg twice daily dose of rebastinib in combination with paclitaxel.
The recommended Phase II dose (RP2D) will be identified of the rebastinib and paclitaxel combination for patients with advanced or metastatic solid tumours that do not respond to standard therapies.
Part two will evaluate the safety, tolerability and efficacy of the RP2D of rebastinib in combination with weekly paclitaxel across multiple cancer types, including breast cancer, ovarian cancer, and endometrial cancer.
The trial will enrol 36 patients for part one and up to 132 for part two.
Primary endpoint of both parts of the trial is adverse events. Part two also includes an additional primary endpoint of objective response rate (ORR).
The trial’s secondary endpoints include maximum observed concentration (Cmax) of rebastinib, area under the concentration-time curve (AUC) of rebastinib, progression-free-survival (PFS) and overall survival (OS).
Deciphera Pharmaceuticals president and CEO Michael Taylor said: “In preclinical testing rebastinib has shown activity as a single agent and when combined with paclitaxel, we observed synergistic reductions in circulating tumour 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 Ib/II clinical trial with paclitaxel, we intend to initiate a second Phase Ib/II clinical trial of rebastinib in combination with carboplatin in the coming months.”
Rebastinib is currently under development as an orally administered selective inhibitor of TIE2 kinase, the receptor for angiopoietins, which is an important vascular growth factor in the tumour microenvironment.