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.
Level 2 - randomized trial
Randomized, placebo-controlled phase 2 clinical trial
PubMed 22700995 · doi:10.1093/annonc/mds142
What was done
Patients with previously untreated metastatic pancreatic adenocarcinoma and ECOG performance status ≤1 (n = 125) were randomized 1:1:1 to receive intravenous gemcitabine (1000 mg/m² on days 1, 8, and 15 every 28 days) combined with open-label ganitumab (12 mg/kg Q2W), double-blind conatumumab (10 mg/kg Q2W), or double-blind placebo Q2W. The primary endpoint was the 6-month survival rate.
What was found
The 6-month survival rates were 57% (95% CI 41–70%) in the ganitumab arm, 59% (95% CI 42–73%) in the conatumumab arm, and 50% (95% CI 33–64%) in the placebo arm. Grade ≥3 adverse events across the ganitumab, conatumumab, and placebo arms, respectively, included neutropenia (18% vs 22% vs 13%), thrombocytopenia (15% vs 17% vs 8%), fatigue (13% vs 12% vs 5%), alanine aminotransferase increase (15% vs 5% vs 8%), and hyperglycemia (18% vs 2% vs 3%).
Why it matters
This study provides early comparative safety and efficacy signals for targeting IGF-1R or death receptor 5 alongside standard gemcitabine in metastatic pancreatic cancer.
Limits
The sample size was small with 125 patients divided across three arms, resulting in wide and overlapping confidence intervals. Ganitumab was administered open-label rather than double-blinded, introducing potential risk of bias. The abstract does not report p-values or formal statistical significance testing for survival differences.
Cited by
- context Amgen conducted a Phase 2 trial of an IGF receptor antibody in advanced pancreatic cancer that failed despite reducing IGF levels at the receptor by 50%, and the antibody does not cross the blood-brain barrier.