Zanzalintinib Versus Everolimus in Participants With Locally Advanced or Metastatic Neuroendocrine Tumors

• Zanzalintinib (Drug), also known as XL092: Administered as specified in the treatment arm.
• Everolimus (Drug), also known as Afinitor: Administered as specified in the treatment arm.

Primary outcomes

• Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version (RECIST) 1.1 as Assessed by Blinded Independent Central Review (BICR) [Up to 48 months]

Secondary outcomes

• PFS Per RECIST 1.1 as Assessed by Investigator [Up to 48 months]
• Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by BICR and Investigator [Up to 48 months]
• Overall Survival (OS) [Up to 60 months]
• Duration of Response (DOR) Per RECIST 1.1 as Assessed by BICR and Investigator [Up to 48 months]
• Disease Control Rate (DCR) Per RECIST 1.1 as Assessed by BICR and Investigator [Up to 48 months]
• Change From Baseline in Participant-Reported Global Health Status (GHS) and Disease-Related Symptoms as Assessed by European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30) Score [Up to 48 months]
• Change From Baseline in Participant-Reported GHS and Disease-Related Symptoms as Assessed by EORTC Gastrointestinal Neuroendocrine Tumor module (QLQ-GI.NET21) Score [Up to 48 months]
• Number of Participants With Adverse Events [Up to 48 months]

Sex: All, ages: 18 Years to any

Key Inclusion Criteria:

* Histologically confirmed, locally advanced/unresectable or metastatic, well-differentiated Grade 1, 2, or 3 NETs of pancreatic origin or extra-pancreatic origin.
* Allowed prior lines of therapy, based on the site of NET and functional status.
* Documented radiographic disease progression per RECIST 1.1, as assessed by the Investigator based on imaging assessments (computed tomography \[CT\] or magnetic resonance imaging \[MRI\]) within 12 months before randomization.
* Measurable disease according to RECIST 1.1 as determined by the Investigator.
* Archival tumor tissue is required, if available. If archival tumor tissue is not available, a fresh biopsy may be submitted if it can be safely and feasibly obtained. Every attempt should be made to provide tumor tissue.

Key Exclusion Criteria:

* Histologically confirmed neuroendocrine carcinomas (including small cell lung cancer), medullary thyroid cancer, pheochromocytoma, paraganglioma, Merkel cell carcinoma, and mixed neuroendocrine non-neuroendocrine neoplasm (MiNEN).
* Prior treatment with a vascular endothelial growth factor receptor (VEGFR) -targeting tyrosine kinase inhibitor or a mammalian target of rapamycin (mTOR) inhibitor.
* Systemic chemotherapy and any liver-directed or other ablative therapy within 4 weeks before randomization.
* Systemic radionuclide therapy within 6 weeks before randomization.
* Radiation therapy for bone metastases within 2 weeks, any other radiation therapy, except as indicated above, within 4 weeks before randomization.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

31 more sites not listed.

• Results publication: Chan JA, Strosberg JR, Yoo C, Singh S, Huang H, Goel M, Scheffold C, Capdevila J. STELLAR-311: a randomized phase II/III study of zanzalintinib versus everolimus in advanced neuroendocrine tumors. Future Oncol. 2026 Sep 28:1-8. doi: 10.1080/14796694.2026.2733790. Online ahead of print. PMID 42803451

• Medical Director, Study director, Exelixis

NIH grants: 2025