A phase 1b, open-label study of trebananib plus bevacizumab or motesanib in patients with solid tumours.

Abstract

BACKGROUND:

To examine the angiopoietin pathway inhibitor trebananib IV plus the anti-VEGF agents bevacizumab or motesanib in advanced solid tumours.

METHODS:

In this open-label phase 1b study, patients received IV trebananib 3 mg kg-1 QW plus bevacizumab 15 mg kg-1 Q3W (cohort 1) or motesanib orally 75 mg (cohort 2); or trebananib 10 mg kg-1 plus bevacizumab 15 mg kg-1 (cohort 3) or motesanib 125 mg (cohort 4). If <33% of patients had dose-limiting toxicities (DLTs), dose escalation occurred. Endpoints were treatment-related adverse events (AEs) incidence and pharmacokinetics (primary); anti-trebananib antibodies, biomarkers, and tumour response (secondary).

RESULTS:

Thirty-six patients received ≥ 1 dose of trebananib (cohorts 1, 2, 3, 4; n = 6, 8, 19, 3). DLT of G3 intestinal perforation and G3 tumor haemorrhage occurred in cohorts 2 and 3, respectively (both n = 1). Across both trebananib plus bevacizumab cohorts, the most common AEs included fatigue (n = 8), diarrhoea (n =4), constipation (n = 3), nausea (n = 3), and epistaxis (n = 3). Three patients across those cohorts had grade ≥ 3 AEs. Across the trebananib plus motesanib cohorts, the most common AEs included hypertension (n = 4), diarrhoea (n = 4), nausea (n = 3), fatigue (n = 3), vomiting (n = 2), and decreased appetite (n = 2). Two patients had grade ≥ 3 AEs. Trebananib did not markedly affect motesanib pharmacokinetics. Across the trebananib plus bevacizumab cohorts, two patients had a partial response; 11 patients had stable disease lasting >6 months. Across the trebananib plus motesanib cohorts, one patient had a partial response; five patients had stable disease lasting >6 months.

CONCLUSION:

Trebananib IV 3 mg kg-1 or 10 mg kg-1 plus bevacizumab or motesanib in advanced solid tumours may be associated with less severe toxicities relative to those emerging when combining two anti-VEGF agents.

• Authors: David S Hong, Razelle Kurzrock, Marilyn Mulay, Erik Rasmussen, Benjamin M Wu, Michael B Bass, Zhandong D Zhong, Greg Friberg, Lee S Rosen
• Journal: Oncotarget (Oncotarget) Vol. 5 Issue 22 Pg. 11154-67 (Nov 30 2014) ISSN: 1949-2553 [Electronic] United States
• PMID: 25525888 (Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal, Humanized
• Indoles
• Oligonucleotides
• Recombinant Fusion Proteins
• Niacinamide
• Bevacizumab
• imetelstat
• trebananib

Topics

• Adult
• Aged
• Aged, 80 and over
• Antibodies, Monoclonal, Humanized (administration & dosage, adverse effects)
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Bevacizumab
• Cohort Studies
• Dose-Response Relationship, Drug
• Female
• Humans
• Indoles (administration & dosage, adverse effects)
• Male
• Middle Aged
• Neoplasms (drug therapy)
• Niacinamide (administration & dosage, adverse effects, analogs & derivatives)
• Oligonucleotides
• Recombinant Fusion Proteins (administration & dosage, adverse effects)