Endocrine Abstracts

Background: Somatostatin analogues (SSAs) are first-line standard of care therapies for gastroenteropancreatic neuroendocrine tumors (GEP-NET), showing efficacy in tumor/symptom control with an established safety profile. Yet, disease progression may occur despite standard-dose SSA treatment, requiring more aggressive and toxic therapies. Retrospective/non-randomized data suggest higher-dose SSAs may benefit patients with GEP-NET 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), and maintenance/reduction of NET symptoms. Prospective, randomized data are needed to confirm the efficacy/safety of novel SSAs with higher bioavailability such as CAM2029, vs standard-dose SSAs including octreotide LAR and lanreotide Autogel (ATG).

Methods: SORENTO is a randomized, multi-center, open-label, active-controlled Phase 3 trial, aiming to enroll 302 adults with GEP-NET. Key eligibility criteria: advanced, well-differentiated NET of GEP/presumed GEP origin; ≥1 measurable SR positive (by nuclear imaging) lesion according to RECIST 1.1; no or <6 months consecutive treatment with long-acting SSAs. Notably, patients with Grade 3 GEP-NET (excluded by CLARINET/PROMID trials) are eligible. Patients will be randomized 1:1 to CAM2029 20mg Q2W, or active comparator (octreotide LAR 30mg intramuscular or lanreotide ATG 120mg SC, Q4W). CAM2029 self/carer administration is allowed after ≥3 successful supervised administrations. Randomization stratified by: histological grade, tumor origin, intended comparator. Primary outcome: progression free survival (PFS; time from randomization 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; response rate; rescue medication use; patient satisfaction; adverse events. After primary PFS analysis, patient overall survival will be followed for up to 2 years. If CAM2029 displays superiority in the primary analysis, the comparator group may switch to CAM2029 20mg Q2W. Patients in any treatment group experiencing progressive disease in the randomized part of the study may proceed to an open-label extension with intensified CAM2029 treatment, to investigate effects of higher frequency dosing. First patient randomized in Nov-2021, with readout (following 194 events) expected by 2024 end. This novel head-to-head superiority trial is anticipated to demonstrate the potential benefits of CAM2029 as a first line-therapy in patients with well-differentiated GEP-NET.

Results: Patient enrollment began Nov-2021; readout expected by end of 2024.

Conclusion: Trial in progress. ClinicalTrials.gov: NCT05050942.

Abstract ID 21419