A phase Ib/II, dose-escalating, safety, and efficacy study of imprime PGG and cetuximab in patients with advanced colorectal cancer (CRC).

Abstract

e14103 Background: Imprime PGG (Imprime PGG Injection) is a beta-glucan polymer being developed for treatment of cancer in combination with complement-activating monoclonal antibodies. A sequential 2-arm study in CRC patients (pts) evaluated the effects of Imprime PGG administered in combination with cetuximab plus irinotecan (Arm 1) and in combination with cetuximab alone (Arm 2). Results of Arm 1 were previously reported (JCO 27, 2009; abstr e15062). Results of the recently completed Arm 2 are presented here. Methods: Pts with recurrent/progressive CRC (Karnofsky ≥ 70%) previously treated with 5-FU (alone or combined with other therapies) were treated weekly with cetuximab (loading dose 400 mg/m2, then 250 mg/m2) and Imprime PGG and were evaluated in 6-wk cycles. Imprime PGG dosing started at 2 mg/kg and escalated to 4 and 6 mg/kg after safety review. Safety (primary endpoint) was assessed by adverse events (AEs) and efficacy (secondary endpoint) by RECIST. Results: Imprime PGG was dosed in 4 pts at 2 mg/kg and in 9 pts each at 4 and 6 mg/kg. Median age was 57. Of the 22 pts enrolled, 1 pt was discontinued in Week 6 due to protocol violations and 21 pts completed the study. No protocol-defined dose-limiting toxicities were observed. AEs experienced by > 25% of pts included acneiform rash (82%); AST increase (50%), ALP increase, ALT increase, bilirubin increase, and leukocytosis (each 46%); bicarbonate decrease, hypokalemia, paronychia, and pedal edema (each 41%); dry skin and GGT increase (each 36%); anemia and uric acid increase (each 32%); and amylase increase, ANC increase, and hyponatremia (each 27%). No related grade 3 or 4 SAEs were reported. In the per protocol population (n = 21), the overall objective response rate (ORR) was 24% (5 pts), the stable disease rate (SD) was 38% (9 pts) and the disease control rate (ORR + SD) was 62% (13 pts). The median time to progression was 12 wks. Conclusions: Imprime PGG combined with cetuximab in CRC pts was safe and efficacy warrants further investigation. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Biothera Biothera Biothera