A Phase 3 Trial of Ganitumab with Gemcitabine as First-Line Treatment of Metastatic Pancreatic Cancer: A Safety Update from the Gamma Trial

ABSTRACT Background Ganitumab is an investigational, fully human, monoclonal antibody inhibitor of IGF1R. In a randomized, phase 2 study in patients with metastatic pancreatic cancer (MPC), the addition of ganitumab 12 mg/kg every 2 weeks to gemcitabine (G) prolonged progression-free survival (PFS) and overall survival (OS) (Kindler H, et al. Ann Oncol 2010; 21: 741P). GAMMA (GEM and AMG 479 in Metastatic Adenocarcinoma of the Pancreas) is assessing the safety and efficacy of ganitumab plus G as first-line treatment (tx) in MPC patients (ClinicalTrials.gov ID: NCT01231347). Methods This is an ongoing, global, phase 3, double-blind study. Patients are randomized 2:2:1 to receive placebo, ganitumab 12 mg/kg, or ganitumab 20 mg/kg (IV; days 1 and 15 Q28D) with G 1000 mg/m2 (IV; days 1, 8, and 15 Q28D). The planned sample size is 825. Key eligibility criteria: untreated metastatic adenocarcinoma of the pancreas, ECOG score ≤1, ≥18 years old, adequate organ function, and fasting (or non-fasting) glucose ≤160 mg/dl. Primary end point: OS. Key secondary end points: PFS, 1-year survival rate, patient-reported outcomes, and safety. Patients receiving 20 mg/kg ganitumab are expected to achieve ganitumab levels above the median in phase 2. A log-rank test stratified by ECOG, presence of liver metastases, and geographic region will compare OS independently for each ganitumab arm at an overall one-sided 2.5% significance level for declaring superiority of ganitumab plus G versus placebo plus G. This study includes multiple planned safety analyses conducted by an independent data monitoring committee. The current predefined safety analyses occurred when 150 patients received ≥1 cycle of tx. Results As of 16 September 2011, 207 patients are included in this aggregate analysis: 50% male; median age, 63 years (range 36–83); ECOG score 0/1, 50%/50%. Of the 207 patients, 204 patients received study tx, and 61 patients ended study tx. Ten patients (5%) died during or within 30 days of the end of tx. Seven events were attributed to or associated with disease progression. One event of cardiac failure was reported to be possibly tx related. Pulmonary embolism was suspected but not confirmed. Conclusions The GAMMA study continues as per protocol. The only grade 3/4 adverse event occurring in more than 5% of patients to date is neutropenia.