Efficacy and safety of a novel oral anti-vasculogenic mimicry agent, CVM-1118, in advanced well-differentiated neuroendocrine tumors: a Phase IIa trial

BACKGROUND: Highly vascularised neuroendocrine tumours (NETs) are attractive targets for foslinanib (CVM-1118), which disrupts vasculogenic mimicry and induces apoptosis via tumour necrosis factor receptor-associated protein 1. We evaluated the efficacy and safety of CVM-1118 in advanced NETs. METHODS: Patients with grades 1-2, well-differentiated lung, gastrointestinal, or pancreatic NETs, refractory or intolerant to one or more standard therapies and progressing within 6 months, received CVM-1118 (200-300 mg orally twice daily) in 28-day cycles. Primary endpoint was progression-free survival (PFS); secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. RESULTS: Of 43 enroled participants, 35 were efficacy-evaluable; most had grade 2 pancreatic (63%) or gastrointestinal (34%) NETs with two prior therapies. Median PFS was 10.5 months (95% CI, 5.6-22.3). ORR was 3%, DCR was 77%, and median OS was not reached (95% CI, 23.8-NR). Sensitivity analysis in the full analysis set (N = 43) showed a PFS estimate broadly aligned with the primary analysis (median, 8.4 months); patients with prior everolimus, sunitinib, or peptide receptor radionuclide therapy (N = 22; median, 8.3 months) showed similar findings. Treatment-related adverse events occurred in 44%, mostly grades 1-2, with no serious events. CONCLUSIONS: CVM-1118 demonstrates favourable efficacy and safety in advanced NETs. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT03600233.