RecruitingInterventionalPhase 2/Phase 3

A Phase 2/3, Multicenter, Randomized Open-Label Study of Zanzalintinib vs Everolimus in Participants With Previously Treated, Unresectable, Locally Advanced or Metastatic Neuroendocrine Tumors

NCT ID: NCT06943755Sponsor: ExelixisLast updated: 2026-04-17

Summary

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.

Arms & interventions

DrugZanzalintinib
Administered as specified in the treatment arm.
DrugEverolimus
Administered as specified in the treatment arm.

Outcome measures

Primary

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

Secondary

PFS Per RECIST 1.1 as Assessed by Investigator
Time frame: Up to 48 months
Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by BICR and Investigator
Time frame: Up to 48 months
Overall Survival (OS)
Time frame: Up to 60 months
Duration of Response (DOR) Per RECIST 1.1 as Assessed by BICR and Investigator
Time frame: Up to 48 months
Disease Control Rate (DCR) Per RECIST 1.1 as Assessed by BICR and Investigator
Time frame: 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
Time frame: 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
Time frame: Up to 48 months
Number of Participants With Adverse Events
Time frame: Up to 48 months

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy volunteers: No

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.

Study locations (39)

Exelixis Clinical Site #43

Birmingham, Alabama, 35294

Recruiting

Exelixis Clinical Site #36

Phoenix, Arizona, 85054

Recruiting

Exelixis Clinical Site #42

Tucson, Arizona, 85724

Recruiting

Exelixis Clinical Site #18

Beverly Hills, California, 90211

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Exelixis Clinical Site #16

Los Angeles, California, 90033

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Exelixis Clinical Site #54

Palo Alto, California, 94305

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Exelixis Clinical Site #12

Santa Monica, California, 90404

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Exelixis Clinical Site #29

Vallejo, California, 94589

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Exelixis Clinical Site #19

Washington D.C., District of Columbia, 20007

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Exelixis Clinical Site #35

Jacksonville, Florida, 32224

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Exelixis Clinical Site #11

Tampa, Florida, 33612

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Exelixis Clinical Site #9

Lexington, Kentucky, 40536

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Exelixis Clinical Site #23

Metairie, Louisiana, 70006

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Exelixis Clinical Site #8

Boston, Massachusetts, 02215

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Exelixis Clinical Site #47

Detroit, Michigan, 48202

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Exelixis Clinical Site #1

Grand Rapids, Michigan, 49546

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Exelixis Clinical Site #38

Rochester, Minnesota, 55905

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Exelixis Clinical Site #5

St Louis, Missouri, 63110

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Exelixis Clinical Site #25

Omaha, Nebraska, 68198

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Exelixis Clinical Site #14

Albuquerque, New Mexico, 87131

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Exelixis Clinical Site #59

Buffalo, New York, 14263

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Exelixis Clinical Site #7

New York, New York, 10029

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Exelixis Clinical Site #53

Rochester, New York, 14642

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Exelixis Clinical Site #17

Chapel Hill, North Carolina, 27599

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Exelixis Clinical Site #6

Durham, North Carolina, 27710

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Exelixis Clinical Site #57

Fargo, North Dakota, 58102

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Exelixis Clinical Site #39

Cleveland, Ohio, 44106

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Exelixis Clinical Site #28

Columbus, Ohio, 43221

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Exelixis Clinical Site #27

Portland, Oregon, 97210

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Exelixis Clinical Site #20

Philadelphia, Pennsylvania, 19104

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Exelixis Clinical Site #21

Pittsburgh, Pennsylvania, 15232

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Exelixis Clinical Site #24

Knoxville, Tennessee, 37920

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Exelixis Clinical Site #65

Nashville, Tennessee, 37232

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Exelixis Clinical Site #10

Dallas, Texas, 75264

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Exelixis Clinical Site #15

Salt Lake City, Utah, 84112

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Exelixis Clinical Site #3

Charlottesville, Virginia, 22903

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Exelixis Clinical Site #13

Fairfax, Virginia, 22031

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Exelixis Clinical Site #34

Seattle, Washington, 98109

Recruiting

Exelixis Clinical Site #31

Milwaukee, Wisconsin, 53226

Recruiting