Recruiting

Phase 2

Phase 3

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

Sponsor:

Exelixis

Code:

NCT06943755

Conditions

Pancreatic Neuroendocrine Tumor (pNET)

Extra-Pancreatic Neuroendocrine Tumor (epNET)

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Zanzalintinib

Everolimus

Study Details

Brief 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.

Conditions

Pancreatic Neuroendocrine Tumor (pNET)

Extra-Pancreatic Neuroendocrine Tumor (epNET)

Study ID

NCT06943755

Start date

Jul 21, 2025

Status verified date

Aug, 2026

Completion date

Jun 30, 2029

Anticipated

Primary completion date

Jun 30, 2029

Anticipated

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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 Design

Enrollment

440 participants

Anticipated

Allocation

Randomized

Intervention Model

Sequential

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

active comparator: Everolimus

Participants will receive everolimus oral tablets once daily.

experimental: Zanzalintinib

Participants will receive zanzalintinib oral tablets once daily.

Interventions

Zanzalintinib

Administered as specified in the treatment arm.

Everolimus

Administered as specified in the treatment arm.

Primary outcome measure

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 ]

Central Contacts and Locations

Central contacts

Exelixis Clinical Trials

1-888-EXELIXIS (888-393-5494)druginfo@exelixis.com

Backup or International

650-837-7400

Locations

The University of Alabama at Birmingham

Recruiting

Birmingham, Alabama, United States, 35294

Mayo Clinic Hospital

Recruiting

Phoenix, Arizona, United States, 85054

The University of Arizona Cancer Center

Recruiting

Tucson, Arizona, United States, 85724

Cedars-Sinai Medical Center

Recruiting

Beverly Hills, California, United States, 90211

Norris Comprehensive Cancer Center

Recruiting

Los Angeles, California, United States, 90033

Stanford Cancer Center

Recruiting

Palo Alto, California, United States, 94305

UCLA Health - Santa Monica Cancer Care

Recruiting

Santa Monica, California, United States, 90404

Kaiser Permanente Medical Center

Recruiting

Vallejo, California, United States, 94589

Georgetown University

Recruiting

Washington D.C., District of Columbia, United States, 20007

Mayo Clinic - Florida

Recruiting

Jacksonville, Florida, United States, 32224

AdventHealth Orlando

Recruiting

Orlando, Florida, United States, 32804

Moffitt Cancer Center

Recruiting

Tampa, Florida, United States, 33612

University of Kentucky Markey Cancer Center

Recruiting

Lexington, Kentucky, United States, 40536

East Jefferson General Hospital

Recruiting

Metairie, Louisiana, United States, 70006

Dana-Farber Cancer Institute

Recruiting

Boston, Massachusetts, United States, 02215

Henry Ford Cancer- Detroit

Recruiting

Detroit, Michigan, United States, 48202

The Cancer and Hematology Centers

Recruiting

Grand Rapids, Michigan, United States, 49546

Mayo Clinic

Recruiting

Rochester, Minnesota, United States, 55905

Siteman Cancer Center

Recruiting

St Louis, Missouri, United States, 63110

University of Nebraska Medical Center

Recruiting

Omaha, Nebraska, United States, 68198

University of New Mexico Comprehensive Cancer Center

Recruiting

Albuquerque, New Mexico, United States, 87131

Roswell Park Cancer Institute

Recruiting

Buffalo, New York, United States, 14263

Icahan School of Medicine at Mount Sinai

Recruiting

New York, New York, United States, 10029

University of Rochester Medical Center

Recruiting

Rochester, New York, United States, 14642

University of North Carolina at Chapel Hill

Recruiting

Chapel Hill, North Carolina, United States, 27599

Duke University Medical Center

Recruiting

Durham, North Carolina, United States, 27710

Sanford Roger Maris Cancer Center

Recruiting

Fargo, North Dakota, United States, 58102

University Hospitals Cleveland Medical Center

Recruiting

Cleveland, Ohio, United States, 44106

The Ohio State University Comprehensive Cancer Center

Recruiting

Columbus, Ohio, United States, 43221

Oregon Health and Science University

Recruiting

Portland, Oregon, United States, 97210

University of Pennsylvania

Recruiting

Philadelphia, Pennsylvania, United States, 19104

University of Pittsburgh Medical Center (UPMC) Hillman Cancer Center

Recruiting

Pittsburgh, Pennsylvania, United States, 15232

University of Tennessee Medical Center

Recruiting

Knoxville, Tennessee, United States, 37920

Henry-Joyce Cancer Clinic

Recruiting

Nashville, Tennessee, United States, 37232

Texas Oncology- Baylor Charles A. Sammons Cancer Center

Recruiting

Dallas, Texas, United States, 75264

Huntsman Cancer Institute, University of Utah

Recruiting

Salt Lake City, Utah, United States, 84112

University of Virginia

Recruiting

Charlottesville, Virginia, United States, 22903

Virginia Cancer Specialists - Fairfax Office

Recruiting

Fairfax, Virginia, United States, 22031

Fred Hutchinson Cancer Center

Recruiting

Seattle, Washington, United States, 98109

Froedtert Hospital and the Medical College of Wisconsin

Recruiting

Milwaukee, Wisconsin, United States, 53226

Verspeeten Family Cancer Center - London Health Sciences Centre

Recruiting

London, Canada, N6A 5W9

The Ottawa Hospital Cancer Center

Recruiting

Ottawa, Canada, K1H 8L6

Sunnybrook Health Sciences Centre

Recruiting

Toronto, Canada, M4N 3M5

More Information

Sponsor

Exelixis

Last update posted

Aug 26, 2026

Last verified

Aug, 2026

Keywords

Metastatic Cancer
Locally Advanced Cancer
Neuroendocrine Tumor (NET)

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by Exelixis on 2026-08-26.