Phase 3 Safety Study of Intravenous NEPA, a Novel Fixed Antiemetic Combination of Fosnetupitant and Palonosetron in Patients Receiving Highly Emetogenic Chemotherapy

Abstract

Background

NEPA, an oral fixed combination of the NK1RA netupitant (300mg) and clinically/pharmacologically distinct 5-HT3RA palonosetron (PALO, 0.50mg), is the first fixed 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 well-established in the Phase 2/3 clinical program in 1169 NEPA-treated patients. An intravenous (IV) formulation of the NEPA combination (fosnetupitant 235mg plus PALO 0.25mg) has been developed.

Patients and methods

This randomized, multinational, double-blind, stratified (by sex and country) Phase 3 study [NCT02517021] in chemotherapy-naïve patients with solid tumors assessed the safety of a single dose of IV NEPA infused over 30 minutes 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 (AEs) and electrocardiograms

Results

A total of 404 patients completed 1312 cycles. The incidence and type of treatment-emergent AEs were similar for both treatment groups with the majority of AEs as mild/moderate in intensity. There was no increased incidence of AEs in subsequent cycles in either group. The incidence of treatment-related AEs was similar and relatively low in both groups (12.8% IV NEPA and 11.4% oral NEPA during the entire study), with constipation being the most common (6.4% IV NEPA, 6.0% oral NEPA). No serious treatment-related AEs occurred in either group. No infusion site or anaphylactic reactions related to IV NEPA occurred. No clinically relevant changes in QTc and no cardiac safety concerns were observed.

Conclusions

IV NEPA was well-tolerated with a similar safety profile to oral NEPA in patients with various solid tumors receiving HEC.