A randomized, placebo-controlled phase 2 study of ganitumab (AMG 479) or conatumumab (AMG 655) in combination with gemcitabine in patients with metastatic pancreatic cancer.
BACKGROUND
We evaluated the efficacy and safety of ganitumab (a mAb antagonist of insulin-like growth factor 1 receptor) or conatumumab (a mAb agonist of human death receptor 5) combined with gemcitabine in a randomized phase 2 trial in patients with metastatic pancreatic cancer.


METHODS
Patients with a previously untreated metastatic pancreatic adenocarcinoma and an Eastern Cooperative Oncology Group (ECOG) performance status ≤1 were randomized 1 : 1 : 1 to i.v. gemcitabine 1000 mg/m(2) (days 1, 8, and 15 of each 28-day cycle) combined with open-label ganitumab (12 mg/kg every 2 weeks [Q2W]), double-blind conatumumab (10 mg/kg Q2W), or double-blind placebo Q2W. The primary end point was 6-month survival rate. Results In total, 125 patients were randomized. The 6-month survival rates were 57% (95% CI 41-70) in the ganitumab arm, 59% (42-73) in the conatumumab arm, and 50% (33-64) in the placebo arm. The grade ≥3 adverse events in the ganitumab, conatumumab, and placebo arms, respectively, included neutropenia (18/22/13%), thrombocytopenia (15/17/8%), fatigue (13/12/5%), alanine aminotransferase increase (15/5/8%), and hyperglycemia (18/2/3%).


CONCLUSIONS
Ganitumab combined with gemcitabine had tolerable toxicity and showed trends toward an improved 6-month survival rate and overall survival. Additional investigation into this combination is warranted. Conatumumab combined with gemcitabine showed some evidence of activity as assessed by the 6-month survival rate.
Section of Hematology/Oncology, University of Chicago Medical Center, Chicago. Electronic address: hkindler@medicine.bsd.uchicago.edu.
H L
HL
Kindler
US Oncology Research, Tyler.
D A
DA
Richards
US Oncology Research, Houston.
L E
LE
Garbo
David Geffen School of Medicine at University of California Los Angeles/Translational Oncology Research International Network, Los Angeles.
E B
EB
Garon
Department of Experimental Therapeutics, Greenville Hospital System University Medical Center, Greenville.
J J
JJ
Stephenson
Department of Medicine, University of Miami/Sylvester Comprehensive Cancer Center, Miami.
C M
CM
Rocha-Lima
The Brown University Oncology Group, Rhode Island Hospital, Providence.
H
H
Safran
Cancer Care Associates Medical Group, Inc., Redondo Beach.
D
D
Chan
US Oncology Research, Round Rock.
D M
DM
Kocs
Global Development, Amgen Inc., Thousand Oaks.
F
F
Galimi
Global Development, Amgen Inc., South San Francisco, USA.
J
J
McGreivy
Department of Biostatistics and Epidemiology, Amgen Ltd, Cambridge, UK.
S L
SL
Bray
Global Development, Amgen Inc., Thousand Oaks.
Y
Y
Hei
Global Development, Amgen Inc., Thousand Oaks.
E G
EG
Feigal
Global Development, Amgen Inc., South San Francisco, USA.
E
E
Loh
Department of Medical Oncology/Solid Tumor Oncology, Dana-Farber Cancer Institute, Boston, USA.
C S
CS
Fuchs
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000188:drug therapy; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D010919:Placebos; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors / Q000276:immunology; D015996:Survival Rate; D016896:Treatment Outcome; D000093542:Gemcitabine
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D010919:Placebos; D003841:Deoxycytidine; C554537:conatumumab; C545764:ganitumab; D017526:Receptor, IGF Type 1; D000093542:Gemcitabine