Phase 3 safety evaluation of an intravenous formulation of NEPA, a novel fixed antiemetic combination of fosnetupitant and palonosetron

Abstract

Background: NEPA, an oral fixed combination of the highly selective NK1RA netupitant (300 mg) and clinically/pharmacologically distinct 5-HT3RA palonosetron (PALO, 0.50 mg) is the first fixed-dose antiemetic combination to have been approved. A single oral NEPA capsule plus dexamethasone (DEX) given prior to AC and non-AC highly emetogenic chemotherapy (HEC) showed superior prevention of chemotherapy-induced nausea and vomiting (CINV) over PALO plus DEX for 5 days post-chemotherapy; the safety of NEPA was also well-established in the Phase 2/3 clinical program in 1442 NEPA-treated patients. An intravenous formulation of the NEPA combination (fosnetupitant 260 mg/PALO 0.25 mg) is under development. Methods: This randomized, multinational, double-blind, stratified (by gender and country) Phase 3 study in chemotherapy-naïve patients with solid tumors was designed to assess the safety of a single 30-minute infusion of IV NEPA prior to initial and repeated cycles of HEC. Patients received either IV NEPA or oral NEPA, both with oral DEX on days 1-4. Safety was assessed primarily by treatment-emergent adverse events (TEAEs) and also by laboratory tests, vital signs and ECGs. Results: 404 patients were included in the safety population (203 IV NEPA, 201 oral NEPA) for a total of 1312 exposures. Overall, 53% of patients were male, 99% were white and the mean age was 60 years. Cisplatin was the most frequent HEC (96% of patients) and lung cancer was most common (55% of patients). The TEAE profiles for cycle 1 (Table) and in all cycles were similar for the two treatment groups. There was no increased incidence of TEAEs in subsequent cycles. No clinically relevant changes in QTc and no cardiac safety concerns were seen. No infusion site reactions related to IV NEPA occurred. Conclusions: Intravenous NEPA was shown to be safe and well-tolerated with a similar safety profile to oral NEPA in patients with various solid tumors receiving HEC. (Table Presented).