Zanzalintinib Versus Everolimus in Participants With Locally Advanced or Metastatic Neuroendocrine Tumors (STELLAR-311)

Exelixis

Status and phase: Begins enrollment in 1 month; Phase 3; Phase 2

Conditions: Extra-Pancreatic Neuroendocrine Tumor (epNET); Pancreatic Neuroendocrine Tumor (pNET)

Treatments: Drug: Zanzalintinib; Drug: Everolimus

Study type: Interventional

Funder types: Industry

Identifiers

NCT06943755

2025-521043-20-00 (EU Trial (CTIS) Number)

XL092-311

Details and patient eligibility

About

The primary purpose of this study is to assess the effectiveness of zanzalintinib compared to everolimus in participants with previously treated, unresectable, locally advanced or metastatic neuroendocrine tumors.

Enrollment: 440 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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440 participants in 2 patient groups

Zanzalintinib

Experimental group

Description:

Participants will receive zanzalintinib oral tablets once daily for up to 14 months.

Treatment:

Drug: Zanzalintinib

Everolimus

Active Comparator group

Description:

Participants will receive everolimus oral tablets once daily for up to 14 months.

Treatment:

Drug: Everolimus