Endoglin inhibitor TRC105 with or without bevacizumab for bevacizumab-refractory glioblastoma (ENDOT): a multicenter phase II trial.

Background: Glioblastoma (GBM), the most lethal primary brain tumor, has limited treatment options upon recurrence after chemoradiation and bevacizumab. TRC105 (carotuximab), a chimeric anti-endoglin (CD105) antibody, inhibits angiogenesis and potentiates activity of VEGF inhibitor bevacizumab in preclinical models. This study sought to assess safety, pharmacokinetics, and efficacy of TRC105 for bevacizumab-refractory GBM.

An Open Label Phase Ib Dose Escalation Study of TRC105 (Anti-Endoglin Antibody) with Axitinib in Patients with Metastatic Renal Cell Carcinoma.

Background: TRC105 is an IgG1 endoglin monoclonal antibody that potentiates VEGF inhibitors in preclinical models. We assessed safety, pharmacokinetics, and antitumor activity of TRC105 in combination with axitinib in patients with metastatic renal cell carcinoma (mRCC).

Subjects, Materials, And Methods: Heavily pretreated mRCC patients were treated with TRC105 weekly (8 mg/kg and then 10 mg/kg) in combination with axitinib (initially at 5 mg b.

An open-label phase Ib dose-escalation study of TRC105 (anti-endoglin antibody) with bevacizumab in patients with advanced cancer.

Purpose: Endoglin, an endothelial cell membrane receptor expressed on angiogenic tumor vessels, is essential for angiogenesis and upregulated in the setting of VEGF inhibition. TRC105 is an anti-endoglin IgG1 monoclonal antibody that potentiates VEGF inhibitors in preclinical models. This study assessed safety, pharmacokinetics, and antitumor activity of TRC105 in combination with bevacizumab.

A phase 1 study of TRC102, an inhibitor of base excision repair, and pemetrexed in patients with advanced solid tumors.

Introduction: TRC102 potentiates the activity of cancer therapies that induce base excision repair (BER) including antimetabolite and alkylating agents. TRC102 rapidly and covalently binds to apurinic/apyrimidinic (AP) sites generated during BER, and TRC102-bound DNA causes topoisomerase II-dependent irreversible strand breaks and apoptosis. This study assessed the safety, maximum-tolerated dose (MTD), pharmacokinetics and pharmacodynamics of TRC102 alone and in combination with pemetrexed.

A phase I first-in-human study of TRC105 (Anti-Endoglin Antibody) in patients with advanced cancer.

Purpose: TRC105 is a chimeric IgG1 monoclonal antibody that binds CD105 (endoglin). This first-in-human, phase I, open-label study assessed safety, pharmacokinetics, and antitumor activity of TRC105 in patients with advanced refractory solid tumors.

Patients And Methods: Patients received escalating doses of intravenous TRC105 until disease progression or unacceptable toxicity using a standard 3 + 3 phase I design.

Phase II study of sunitinib malate, an oral multitargeted tyrosine kinase inhibitor, in patients with metastatic breast cancer previously treated with an anthracycline and a taxane.

Purpose: Sunitinib is an oral, multitargeted tyrosine kinase inhibitor that inhibits vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor, stem cell factor receptor (KIT), and colony-stimulating factor-1 receptor. This phase II, open-label, multicenter study evaluated sunitinib monotherapy in patients with metastatic breast cancer (MBC).

Patients And Methods: Sixty-four patients previously treated with an anthracycline and a taxane received sunitinib 50 mg/d in 6-week cycles (4 weeks on, then 2 weeks off treatment).