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

H. L. Kindler, D. A. Richards, L. E. Garbo, E. B. Garon, J. J. Stephenson, 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

Research output: Contribution to journalArticle

115 Scopus citations

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.

Original languageEnglish (US)
Article numbermds142
Pages (from-to)2834-2842
Number of pages9
JournalAnnals of Oncology
Volume23
Issue number11
DOIs
StatePublished - Nov 1 2012

Keywords

  • AMG 479
  • Conatumumab
  • Ganitumab
  • Gemcitabine
  • Pancreatic cancer
  • Phase 2 trial

ASJC Scopus subject areas

  • Oncology
  • Hematology

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    Kindler, H. L., Richards, D. A., Garbo, L. E., Garon, E. B., Stephenson, J. J., Rocha-Lima, C. M., Safran, H., Chan, D., Kocs, D. M., Galimi, F., Mcgreivy, J., Bray, S. L., Hei, Y., Feigal, E. G., Loh, E., & Fuchs, C. S. (2012). 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. Annals of Oncology, 23(11), 2834-2842. [mds142]. https://doi.org/10.1093/annonc/mds142