A randomised, double-blind, placebo-controlled phase 2 study of trebananib (AMG 386) in combination with FOLFIRI in patients with previously treated metastatic colorectal carcinoma

Background: This phase 2 study evaluated trebananib (AMG 386), an investigational peptide-Fc fusion protein that neutralises the interaction between angiopoietins-1/2 and the Tie2 receptor, plus FOLFIRI as second-line treatment for patients with metastatic colorectal cancer. Methods: Patients had adenocarcinoma of the colon or rectum with progression within 6 months of receiving only one prior fluoropyrimidine/oxaliplatin-based chemotherapy regimen for metastatic disease. All patients received FOLFIRI and were randomised 2:1 to also receive intravenous trebananib 10 mg kg(-1) once weekly (OW) (Arm A) or placebo OW (Arm B). The primary end point was investigator-assessed progression-free survival (PFS). Results: One hundred and forty-four patients were randomised (Arms A/B, n = 95/49). Median PFS in Arms A and B was 3.5 and 5.2 months (hazard ratio (HR) 1.23; 95% CI, 0.81-1.86; P = 0.33) and median overall survival (OS) was 11.9 and 8.8 months, respectively (HR 0.90; 95% CI; 0.53-1.54; P = 0.70). Objective response rate (ORR) was 14% and 0% in Arms A and B, respectively. Incidence of grade >= 3 adverse events was similar between treatment arms (Arm A, 61%; Arm B, 65%) and included pulmonary embolism (1%/4%), deep vein thrombosis (5%/2%), and hypertension (1%/0%). Conclusion: Administration of trebananib plus FOLFIRI did not prolong PFS compared with placebo plus FOLFIRI. Toxicities were manageable and consistent with those known for FOLFIRI and trebananib.