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 (QW) (Arm A) or placebo QW (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%).


CONCLUSIONS
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.
Department of Oncology, Antwerp University Hospital, Edegem, Belgium. Marc.Peeters@uza.be
M
M
Peeters
A H
AH
Strickland
M
M
Lichinitser
A V S
AV
Suresh
G
G
Manikhas
J
J
Shapiro
W
W
Rogowski
X
X
Huang
B
B
Wu
D
D
Warner
R
R
Jain
N C
NC
Tebbutt
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis; D002166:Camptothecin / Q000008:administration & dosage; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D004311:Double-Blind Method; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007390:International Agencies; D002955:Leucovorin / Q000008:administration & dosage; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage; D016879:Salvage Therapy; D015996:Survival Rate; D055815:Young Adult
D014408:Biomarkers, Tumor; D011993:Recombinant Fusion Proteins; D002955:Leucovorin; D005472:Fluorouracil; C551398:trebananib; D002166:Camptothecin