STELLAR-311: a randomized phase II/III study of zanzalintinib versus everolimus in advanced neuroendocrine tumors.

Patients with advanced neuroendocrine tumors (NETs) experience poor outcomes despite the use of available therapies, including molecularly targeted agents. Zanzalintinib is a novel, small-molecule inhibitor of multiple kinases, including the TAM kinases (TYRO3, AXL, MER), MET, and vascular endothelial growth factor receptors, which play important roles in oncogenic processes. Zanzalintinib has shown encouraging antitumor activity and a consistent safety profile across multiple solid tumor types in clinical trials. STELLAR-311 is a global, randomized, open-label, phase II/III trial evaluating the efficacy and safety of zanzalintinib versus everolimus in patients with advanced NETs. Adults aged ≥18 years with locally advanced/unresectable or metastatic, well-differentiated grade 1-3 NETs of pancreatic (pNET) or extra-pancreatic (epNET; gastrointestinal tract, lung, thymus, or other) origin will be enrolled. Patients with pNETs or nonfunctional epNETs can be untreated or have received up to one prior line of therapy (excluding somatostatin analogs); patients with functional epNETs must have received one prior line of therapy. The primary endpoint is progression-free survival (PFS), by blinded independent central review (BICR). Secondary endpoints include overall survival; investigator-assessed PFS; BICR- and investigator-assessed objective response rate, duration of response, and disease control rate; safety; and quality of life.Clinical trial registration www.clinicaltrials.gov identifier is NCT06943755.