Abstract C36: MBP-426, a novel liposome-encapsulated oxaliplatin, in combination with 5-FU/leucovorin (LV): Phase I results of a Phase I/II study in gastro-esophageal adenocarcinoma, with pharmacokinetics

Abstract

Abstract Background: MPB-426 is a new transferrin-conjugated liposomal formulation of oxaliplatin, which can provide preferential tumor targeting and better bioavailability through the EPR effect and binding of transferrin receptors, respectively. In a recent phase I study, single agent MBP-426 given q3w showed thrombocytopenia as DLT, with 226 mg/m2 being the recommended phase II dose (RDP2). The current phase I–II study was designed to establish the RDP2 of MPB-426 in combination with 5-FU/LV (de Gramont schedule) and assess the efficacy of this combination in pretreated patients with gastro-esophageal (GE) adenocarcinoma. Methods: MBP-426 IV was given q3w at two dose levels: 226 and 170 mg/m2 with fixed doses of 5-FU/LV. LV (400 mg/m2) was given concurrently with MBP-426 followed by IV bolus 5-FU (400 mg/m2), and then by 5-FU 2400 mg/m2 by continuous IV (CIV) infusion over 46 hours. The phase I dose assessment part was conducted in solid tumor patients. The phase II part will be limited to second line patients with gastric, gastro-esophageal or esophageal adenocarcinoma. Results: The phase I part has been completed. Nine patients (pts) were included and treated. Median age: 61 years (55–67), gender M/F: 5/4, ECOG PS 0/1: 2/7, diagnosis: colorectal 4, pancreas 2, bladder 1, H&N 1 and cervix 1. Median number of prior lines: 4 (2–10). Four patients received a total of 11 cycles at the first dose level (MBP-426 226 mg/m2), in which two dose limiting toxicities (DLTs) were observed: grade 3 nausea and vomiting (1 pt) and grade 3 back pain (1 pt). Additional grade 3–4 toxicities were thrombocytopenia (3 pts), neutropenia (2 pts), transient rise of bilirubin (1 pt), and skin toxicity (1 pt with grade 3 erythema multiforme at cycle 4). To date, six patients (7 cy) have been explored at a lower dose level of 170 mg/m2. No DLTs were observed, establishing 170 mg/m2 as the RDP2. Grade 3–4 toxicity was limited to neutropenia in 1 pt. Oxaliplatin-induced peripheral neuropathy was not reported at either dose level, with 5 pts receiving an oxaliplatin equivalent dose ≥ 500 mg/m2. Efficacy: early data show 2 SD (4 cycles, 4+) and 1 PD (2 cycles) in 3 evaluable colorectal pts, all resistant to prior exposure to oxaliplatin. Pharmacokinetic data will be available for the meeting. Conclusion: MBP-426 at 170 mg/m2 is the RDP2 for use in combination with 5-FU/LV (de Gramont schedule) every 3 weeks. Treatment at this dose was well tolerated. No peripheral neurotoxicity has been reported with this new formulation of oxaliplatin. Potential activity was observed in 2 oxaliplatin-resistant patients. Citation Information: Mol Cancer Ther 2009;8(12 Suppl):C36.