A multicenter, phase II study of CPX-1 liposome injection in patients (pts) with advanced colorectal cancer (CRC)

4108 Background: CPX-1 is a novel, liposomal formulation of irinotecan (IRI) and floxuridine (FLOX). CPX-1 uses principles of fixed drug ratio dosing where synergistic drug ratios for chemotherapy doublets defined in vitro are then encapsulated within carriers that control in vivo pharmacokinetics and maintain the ratio systemically. Methods: Pts with advanced CRC, ECOG PS<2, adequate bone marrow, liver and renal function were eligible for this study (CLTR0105–201). Prior oxaliplatin was allowed. Approximately 30 IRI- naïve patients (Group 1) and 30 IRI-refractory (PD <6 months from last IRI treatment) patients (Group 2) were registered. CPX-1 infusions (90 min, 210 u/m2 (1 u = 1mg IRI and 0.36 mg FLOX)) were administered on Days 1 and 15 every 28 days until PD or toxicity. Dose reductions to 150 and 100 u/m2 were permitted for pts with drug-related grade 3/4 neutropenia and GI toxicities and for some pts with prior intolerance to IRI-based regimens. Response rate (ORR) according to RECIST and progression-free survival (PFS) were evaluated. Results: Study enrollment is closed, 26 patients, 13 male, median age 58 (46–77) yrs were enrolled in Group 1 and 33 (29 evaluable for efficacy), 20 male, median age 59 (36–81) yrs in Group 2. Group 1: ORR is currently 8% and disease control rate (DCR=ORR+SD) is 65%. Median PFS with 5 pts continuing to receive therapy is currently 3.2 months with 9 pts having a >4.0 month PFS. Group 2: Currently, no responses have been observed and DCR was 38%. The median PFS with 9 pts continuing to receive therapy is currently 1.8 months, with 6 patients having a >4.0 month PFS. Safety data are available for 51 pts; 34 (67%) had drug-related grade 3/4 toxicities. Grade 3/4 toxicities in > 2 pts: diarrhea (27%), neutropenia (24%), fatigue (14%), nausea (8%) and hypokalemia (6%). Five pts died on study with one death from pneumonia considered treatment related. Conclusions: CPX-1 is well tolerated and provides clinical benefit to pts with advanced CRC. CPX-1 appears to be more active than FOLFIRI used after FOLFOX (Tournigand) and will be studied further. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Celator Pharmaceuticals, Inc. Celator Pharmaceuticals, Inc. Celator Pharmaceuticals, Inc.