Endocrine Abstracts

Background: Somatostatin receptor ligands (SRLs) are first-line standard-of-care therapies for gastroenteropancreatic neuroendocrine tumours (GEP-NETs), showing efficacy in tumour and symptom control with an established safety profile. However, disease progression may occur despite standard-dose SRL treatment, requiring more aggressive and toxic treatments. Retrospective/non-randomized data suggest higher-dose SRLs may benefit patients with GEP-NETs who do not respond to standard-dose treatment and provide improved disease control. Octreotide depot (CAM2029) is a novel high-exposure, subcutaneous (SC) formulation. Clinical trials showed ~500% higher CAM2029 bioavailability vs octreotide long-acting release (LAR) (Tiberg et al. 2015), and maintenance/reduction of NET symptoms (Pavel et al. 2019). Prospective, randomised trial data are needed to confirm the efficacy/safety of higher-dose SRLs such as CAM2029, vs standard-dose SRLs (including octreotide LAR and lanreotide Autogel [ATG]).

Methods: SORENTO is a randomised, multi-centre, open-label, active-controlled Phase 3 trial, aiming to enrol 302 adults with GEP-NETs. Key eligibility criteria: advanced, well-differentiated NET of GEP/presumed GEP origin; ≥1 measurable and somatostatin receptor-positive (by nuclear imaging) lesion according to RECIST 1.1; no or <6 months consecutive treatment with long-acting SRLs. Notably, patients with well-differentiated Grade 3 GEP-NETs (excluded by CLARINET and PROMID trials) are eligible. Patients will be randomised 1:1 to CAM2029 20 mg every two weeks (Q2W), or active comparator (octreotide LAR 30 mg intramuscular or lanreotide ATG 120 mg SC, every four weeks). CAM2029 self-/carer-administration is permitted after ≥3 supervised/successful administrations. Randomisation stratified by: histological grade, tumour origin and intended comparator. Primary outcome: progression-free survival (PFS; time from date of randomisation to date of first documented disease progression [RECIST 1.1] or death), assessed by a Blinded Independent Review Committee. The study is powered to detect a hazard ratio of 0.65. Key secondary outcomes: overall survival; RECIST 1.1-defined response rate; rescue medication use; patient satisfaction; adverse events. After primary PFS analysis, patients will be followed for up to 2 years for overall survival (if CAM2029 displays superiority in the primary analysis, the comparator group may switch to CAM2029 20 mg Q2W). Patients (in either treatment group) who experience progressive disease in the randomised part of the study may proceed to an open-label extension with intensified CAM2029 treatment, to investigate effects of higher frequency dosing. First patient randomised in Nov-2021; read-out (achieved after 194 events) expected by end of 2024. This novel head-to-head superiority trial is anticipated to demonstrate the potential benefits of CAM2029 as first-line therapy in patients with well-differentiated GEP-NETs. ClinicalTrials.gov identifier: NCT05050942.