Randomized, double-blind phase 3 trial of the fixed-dose combination fosrolapitant/palonosetron (HR20013) plus dexamethasone for prevention of nausea and vomiting in patients receiving moderately emetogenic chemotherapy.

Abstract

11006 Background: Despite antiemetic guidelines, ~50% of patients (pts) receiving moderately emetogenic chemotherapy (MEC) still experience chemotherapy-induced nausea and vomiting (CINV), mainly in the delayed phase (DP, 24-120 h). HR20013 is a fixed-dose IV formulation providing dual NK1 and 5-HT3 receptor blockade in a single dose and showed efficacy in preventing CINV following highly emetogenic chemotherapy in the phase 3 PROFIT trial (Zhou et al., JCO 2025). This study is the first pivotal phase 3 trial to evaluate the efficacy and safety of single-dose HR20013 plus dexamethasone (DEX) in the MEC setting. Methods: In this multicenter, randomized, double-blind, active-controlled phase 3 trial, chemotherapy-naïve adults with solid tumors scheduled for single-day MEC were randomized (1:1) to receive single-dose HR20013 (fosrolapitant 218 mg + palonosetron [PALO] 0.25 mg IV) or placebo + PALO prior to chemotherapy on D1. All pts also received oral DEX 7.5 mg on D1. Primary endpoint was complete response (CR; no emesis, no rescue therapy) in the DP (24–120 h). Key secondary endpoint was CR in the overall phase (OP; 0–120 h). Results: Of 706 randomized pts, the ITT population included 348 in the HR20013+DEX group and 352 in the PALO+DEX group. Baseline characteristics were well balanced. HR20013 showed statistically superior and clinically meaningful efficacy vs active control. CR rate in the DP was 79.0% (95% CI 74.4–83.2) with HR20013+DEX vs 61.4% (95% CI 56.1–66.5) with PALO+DEX (difference 17.8%, 95% CI 11.1–24.4; P < 0.0001). CR rate in the OP was 75.6% (95% CI 70.7–80.0) vs 59.9% (95% CI 54.6–65.1) (difference 15.7%, 95% CI 9.0–22.5; P < 0.0001). HR20013 also showed improved CR rate in acute phase (0-24 h; 92.5% vs 86.1%; P = 0.0052) and consistently showed higher rates across efficacy assessments including no significant nausea, complete protection, and total control in all phases. Time to treatment failure analysis favored HR20013 (HR 0.52, 95% CI 0.40–0.69). Functional Living Index-Emesis indicated that a greater proportion of pts receiving HR20013+DEX reported no impact on daily life in the DP (e.g., 90.2% vs 75.9% in the vomiting domain). The incidence of TRAEs were similar between groups (25.1% for HR20013 vs 21.4% for PALO). Most common TRAEs with HR20013 were constipation (8.9%), hypertriglyceridemia (4.0%), and hiccups (3.5%). Grade ≥3 TRAEs were infrequent (1.2% vs 1.4%). No new safety signals were identified. Conclusions: In pts receiving MEC, a single dose of fixed-dose combination HR20013 plus DEX was well tolerated and demonstrated superior efficacy in preventing CINV compared to the standard regimen of PALO+DEX, with improved patient-reported outcomes. This single-dose, dual-pathway antiemetic offers a more effective and convenient prophylactic option for MEC. Clinical trial information: NCT06554184 .