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Purpose: This phase I study investigated the maximum-tolerated dose (MTD), safety, pharmacodynamics, immunologic correlatives, and antitumor activity of CP-870,893, an agonist CD40 antibody, when administered in combination with gemcitabine in patients with advanced pancreatic ductal adenocarcinoma (PDA).

Experimental Design: Twenty-two patients with chemotherapy-naïve advanced PDA were treated with 1,000 mg/m² gemcitabine once weekly for three weeks with infusion of CP-870,893 at 0.1 or 0.2 mg/kg on day three of each 28-day cycle.

Results: CP-870,893 was well-tolerated; one dose-limiting toxicity (grade 4, cerebrovascular accident) occurred at the 0.2 mg/kg dose level, which was estimated as the MTD. The most common adverse event was cytokine release syndrome (grade 1 to 2). CP-870,893 infusion triggered immune activation marked by an increase in …