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
e15062 Background: Imprime PGG (Imprime PGG Injection) is a ß-glucan polymer being developed for treatment of cancer in combination with complement-activating monoclonal antibodies. This trial evaluates the safety and efficacy of Imprime PGG in combination with cetuximab and irinotecan in CRC patients (pts). Methods: Pts with recurrent/progressive CRC (Karnofsky > 70%) previously treated with 5-FU (alone or combined with other therapies) were treated with Imprime PGG (weekly), cetuximab (weekly; loading dose 400 mg/m2, then 250 mg/m2), and irinotecan (wks 1–4 of each 6-wk cycle; 125 mg/m2). In a 3 + 3 design, 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 3 pts at 2 mg/kg, 6 pts at 4 mg/kg and 1 pt at 6 mg/kg. Median age was 56. One pt remains on therapy at wk 49; other pts exited due to progressive disease (5 pts), irinotecan intolerance (2 pts), investigator discretion (1 pt), and withdrawn consent (1 pt). Median duration of treatment was 17.5 wks. No protocol-defined dose-limiting toxicities were observed. AEs experienced by > 50% of pts included diarrhea (90%), hypokalemia, neutropenia (80%), weight loss (70%), anemia, anorexia, leucopenia (60%), alopecia, dry skin, hypomagnesemia, increased amylase, vomiting (50%). Grade 4 SAEs included increased amylase, increased lipase, and neutropenia. Partial response (PR) occurred in 3 pts (30%) and stable disease (SD) in 7 pts (70%), yielding a disease control rate (PR + SD) of 100%. The median time to progression was 22.3 wks. Conclusions: Imprime PGG combined with cetuximab and irinotecan in CRC pts was safe and efficacy warrants further investigation. [Table: see text]
Aim: Investigate the safety, pharmacokinetics (PK) and efficacy of BTH1677/cetuximab, with and without irinotecan, in patients with metastatic colorectal cancer (mCRC). Patients & methods: Patients with recurrent or progressive mCRC were assigned to BTH1677/cetuximab/irinotecan (group 1; n = 10) or BTH1677/cetuximab (group 2; n = 22). Adverse events, PK parameters and tumor response were assessed. Results & conclusion: Adverse events were consistent with those expected of the backbone therapy of cetuximab/irinotecan (group 1) or cetuximab alone (group 2). The BTH1677 PK profiles were similar in the two groups. The overall response rates were 30.0% (group 1) and 22.7% (group 2); in KRAS wild-type subset analysis, rates were 42.9% and 45.5%, respectively. BTH1677 therapy was tolerable and warrants further evaluation for treatment of mCRC.
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