A phase 1b study of trebananib in combination with pegylated liposomal doxorubicin or topotecan in women with recurrent platinum-resistant or partially platinum-sensitive ovarian cancer

Abstract

Objective. To examine the tolerability and antitumor activity of trebananib plus pegylated liposomal doxorubicin (PLD) or topotecan in recurrent platinum-resistant or partially platinum-sensitive ovarian cancer.Methods. In this open-label phase 1b study, patients received trebananib 10 mg/kg or 15 mg/kg IV QW plus PLD 50 mg/m 2 (cohorts A1 and A3, respectively) or topotecan 4 mg/m 2 (cohorts B1 and B3, respectively). Endpoints were dose-limiting toxicity (DLT; primary); treatment-emergent adverse events (AEs), overall response rate, anti-trebananib antibodies, and pharmacokinetics (secondary).Results. 103 patients were enrolled. One patient in A1 and B1 had DLTs. Across all cohorts, the most common AEs were nausea, fatigue, and peripheral edema. Across both trebananib plus PLD cohorts (A1/A3), grade 4 AEs were pulmonary embolism, disease progression, and anemia. Two patients had grade 5 intestinal perforation (n = 1) and sudden death (n = 1). Across both trebananib plus topotecan cohorts (B1/B3), grade 4 AEs were neutropenia, hypokalemia, decreased granulocyte count, chest pain, dyspnea, decreased neutrophil count, and pulmonary embolism. Two patients had grade 5 disease progression. One patient had grade 5 pleural effusion associated with progressive disease. Confirmed objective response rates were 36.0% (A1), 34.8% (A3), 16.7% (B1), and 0.0% (B3). Median progression-free survival duration (months) was 7.4 (A1), 7.1 (A3), 3.5 (B1), and 3.1 (B3), respectively. No drug-drug interactions were apparent.

Topotecan synergizes with CHEK1 (CHK1) inhibitor to induce apoptosis in ovarian cancer cells

“…TPT has been combined clinically with angiogenesis inhibitors bevacizumab or trabananib [ 21 , 22 ]. Such a strategy combines agents targeting two separate pathways (DNA replication and angiogenesis) important to cancer, without overlapping side effects so as not to limit dosage of either drug.…”

Phase 2 and biomarker study of trebananib, an angiopoietin‐blocking peptibody, with and without bevacizumab for patients with recurrent glioblastoma

“…20 Early clinical trials demonstrated encouraging antitumor activity of trebananib in patients with various types of solid tumors. [21][22][23][24] In the current phase 2 study, we evaluated intravenous trebananib (30 mg/kg weekly) administered as single agent and in combination with intravenous bevacizumab (10 mg/kg biweekly) for patients with recurrent glioblastoma. Circulating biomarkers of angiogenesis and inflammation were evaluated to explore potential biomarkers that could be used to enable rational patient selection in future studies.…”

Epithelial Ovarian Cancers: On-Target is Better than Near-Target

“…Two phase I studies have shown that Trebananib in combination with liposomal doxorubicin, topotecan or paclitaxel carboplatin has some clinical effectiveness [39,40]. This was later confirmed by a phase III trial, the TRINOVA 1 study, where recurrent ca ovary with platinum free interval less than a year was randomized to single agent paclitaxel or combination with Trebananib.…”