Phase 2 study of nab-sirolimus in patients with well-differentiated and advanced/metastatic neuroendocrine tumors of the gastrointestinal tract, lung, or pancreas.

Abstract

TPS601 Background: Neuroendocrine tumors (NETs; ~2% of all malignancies) commonly arise from the gastrointestinal (GI) tract, pancreas, and lung, often presenting as metastatic disease. The PI3K/Akt/mTOR pathway is implicated in the pathogenesis and progression of NETs. Everolimus, an oral mTOR inhibitor (mTORi), is an option for treatment of NETs of the GI tract, lung, or pancreas but response rates observed in the RADIANT -3 and -4 studies were modest at 4–10%. nab-Sirolimus is a mTORi that utilizes nanoparticle technology to preferentially target tumors and is approved in the USA for malignant perivascular epithelioid cell tumor. In preclinical animal models, nab-sirolimus demonstrated higher intratumoral drug accumulation, improved target suppression, and stronger antitumor activity relative to equal weekly doses of sirolimus and everolimus, warranting further exploration of nab-sirolimus. This study will evaluate efficacy/safety of nab-sirolimus in patients with advanced/metastatic NETs. Methods: This phase 2, multicenter, open-label, single-arm study (NCT05997056) will enroll approximately 21 adults (≥18 years) with functional or non-functional, well-differentiated, locally advanced unresectable or metastatic NETs of the GI tract, lung, or pancreas who have received ≤2 prior lines of therapy, excluding somatostatin analogs (SSTa).Patients with functional NETS are eligible if they have been on a stable dose of SSTa for ≥12 weeks and had disease progression during SSTa treatment. Eligible patients must have ≥1 measurable target lesion (per Response Evaluation Criteria in Solid Tumors [RECIST] v1.1), Eastern Cooperative Oncology Group performance status score 0 or 1, and adequate organ function/hematologic parameters.They are not permitted to have received prior mTORi, including nab-sirolimus, or to have tumors with known inactivating TSC1 or TSC2 alterations. Patients will receive nab-sirolimus 100 mg/m2 by intravenous infusion on days 1 and 8 of 21-day cycles. Treatment will continue until disease progression or unacceptable toxicity, or until discontinuation based on investigator or patient discretion.The primary endpoint is investigator-assessed objective response rate per RECIST v1.1. Secondary endpoints include duration of response, disease control rate, time to response, progression-free survival, overall survival, and safety. Exploratory endpoints include correlation of baseline molecular biomarkers with clinical outcomes. Analysis of study objectives will be descriptive. Study site activation is underway with the first patient on study anticipated for the 3rd quarter of 2023. Clinical trial information: NCT05997056 .