CAREFNDR: A phase III, randomised, parallel group, placebo-controlled study to evaluate the efficacy and safety of paltusotine in adults with carcinoid syndrome due to well-differentiated neuroendocrine tumours

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Introduction: Paltusotine is a once-daily, oral, nonpeptide, selective SST2 receptor agonist in development for carcinoid syndrome (CS) treatment. In a Phase 2, open-label, dose-ranging study, paltusotine reduced the frequency and severity of CS symptoms and was well tolerated (NCT05361668).

Aim(s): CAREFNDR will evaluate the efficacy and safety of paltusotine vs. placebo in participants with CS.

Materials and methods: Eligibility: participants with documented, grade I/II NETs with CS who are either naïve to somatostatin receptor ligands (SRLs) or untreated for ≥4 months and actively symptomatic [>1 flushing episode/day (14-day average) and plasma 5HIAA or serotonin ≥2 x ULN], or have symptom control on SRLs [average ≤2 flushing episodes/day and ≤3 bowel movements (BMs)/day in first 2-week injection cycle] and have symptom worsening after SRL washout [increase in average flushing episodes/day and >1 flushing episode/day (14-day average)]. Approximately 141 participants will be randomised 2:1 to paltusotine 80 mg or placebo for 16 weeks [randomised controlled period (RCP)]. Participants may enter the open-label extension (OLE) and receive paltusotine for 104 weeks. Primary endpoint will be the treatment-group difference in change from baseline to week 12 in flushing episodes/day (14-day average). Key secondary endpoint will be change from baseline in BMs/day. Safety and tolerability assessments will include incidence of TEAEs and changes in safety parameters. A de novo CS Symptom Diary of 7 of the most impactful CS symptoms will be completed daily during screening and the RCP, and periodically throughout OLE. Participants may take rescue medication during the RCP based on protocol-standardised criteria. Global enrolment in CAREFNDR is expected throughout 2025.

Conference:

Presenting Author:

Authors: Kim R, Usiskin K, Fan X, Quock T, Mui C,

Keywords: paltusotine, phase 3 trial, somatostatin receptor agonist, neuroendocrine tumour, carcinoid syndrome,