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.

Abstract

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.

PATIENTS AND 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.

• Authors: H L Kindler, D A Richards, L E Garbo, E B Garon, J J Stephenson Jr, C M Rocha-Lima, H Safran, D Chan, D M Kocs, F Galimi, J McGreivy, S L Bray, Y Hei, E G Feigal, E Loh, C S Fuchs
• Journal: Annals of oncology : official journal of the European Society for Medical Oncology (Ann Oncol) Vol. 23 Issue 11 Pg. 2834-2842 (Nov 2012) ISSN: 1569-8041 [Electronic] England
• PMID: 22700995 (Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Placebos
• Deoxycytidine
• conatumumab
• ganitumab
• Receptor, IGF Type 1
• Gemcitabine

Topics

• Adenocarcinoma (drug therapy, mortality, secondary)
• Adult
• Aged
• Aged, 80 and over
• Antibodies, Monoclonal (administration & dosage, adverse effects)
• Antibodies, Monoclonal, Humanized
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Deoxycytidine (administration & dosage, adverse effects, analogs & derivatives)
• Female
• Humans
• Male
• Middle Aged
• Neoplasm Metastasis (drug therapy)
• Pancreatic Neoplasms (drug therapy, mortality, pathology)
• Placebos
• Receptor, IGF Type 1 (antagonists & inhibitors, immunology)
• Survival Rate
• Treatment Outcome
• Gemcitabine