Second interim analysis of CABONEN: An international, multicenter phase II trial investigating cabozantinib in patients with advanced, low proliferative NEN G3.

Abstract

e16351 Background: The prognosis of patients with neuroendocrine neoplasia (NEN) depends mainly on the proliferation index (Ki67). Patients with NEN G1 and G2 frequently survive many years, while those with NEN G3 often die within 12 months after diagnosis. For patients with NET G1/G2, a few approved treatment options are available, while for NEN G3 the choice is very limited. Among NEN G3, those with a Ki67 of > 60% respond well to platinum-based chemotherapies, while there is no trial-proven treatment option for slower-proliferating G3 tumors. The CABONEN study evaluates the tyrosine kinase inhibitor Cabozantinib, which has shown striking activity in NEN G1/G2, in NEN G3 with a Ki67 up to 60%. Here we present the efficacy and tolerability outcomes of the second per-protocol planned interim analysis. Methods: CABONEN represents a prospective, single-arm, multicenter phase II trial investigating the efficacy and safety of Cabozantinib in NEN G3 patients with a Ki67 between 20% and 60%. Primary endpoint is disease control rate (DCR) after 6 months; secondary endpoints include DCR after 3 and 12 months, progression free survival (PFS), overall survival (OS), objective response rate (ORR), time on medication (TOM), quality of life, and toxicity. Results: From December 2021 to December 2024, all 45 planned patients (21 female, 24 male) were enrolled although not all patients have reached 6 month of treatment for the primary endpoint. Of these, 39 patients had NET G3, and 6 patients had NEC Ki67low. The median age at diagnosis was 63 years (40 to 84 years). The primary tumor location was the pancreas in 53.3% (24), the GI tract in 20% (9) lung in 11.1% (5), and others in 15.5 % (7). The median Ki67 was 31% (21% to 60%). Twelve patients were therapeutically naïve (26.7%), 13 had received 1 prior therapy (28.9%) and 20 had received 2 or more therapeutic lines (44.4%). The primary end point DCR at 6 months was 83% and at 3 months 92.1% The best objective response rate was 19.5% and the median PFS was 9.7 months. During therapy, a total of 105 SAEs were observed including 74 SAE grade 3, 1 SAE grade 4, and 4 SAE grade 5, with SAEs being ileus, acute pain, cholangiosepsis, infection, small intestinal perforation, or stroke. A Data and Safety Monitoring Board could not find any new and unexpected (S)AEs and recommends continuation of the study. Conclusions: At interim analysis, Cabozantinib represents a safe and effective treatment option in patients with low proliferative NEN G3. The CABONEN study will continue to the next planned analysis. Clinical trial information: EudraCT Number: 2020-002541-41 .