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

RecruitingPhase 2/3

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

Who can join

Ages 18 and older · All sexes

Full eligibility 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.

About the study

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.

What is being tested

Sponsor: Exelixis · Participants: 440 · Started: Jul 21, 2025

Contact the study team

Official record on ClinicalTrials.gov — NCT06943755

Locations in the U.S.

AlabamaThe University of Alabama at Birmingham, Birmingham
ArizonaMayo Clinic Hospital, Phoenix
The University of Arizona Cancer Center, Tucson
CaliforniaCedars-Sinai Medical Center, Beverly Hills
Norris Comprehensive Cancer Center, Los Angeles
Stanford Cancer Center, Palo Alto
UCLA Health - Santa Monica Cancer Care, Santa Monica
Kaiser Permanente Medical Center, Vallejo
District of ColumbiaGeorgetown University, Washington D.C.
FloridaMayo Clinic - Florida, Jacksonville
AdventHealth Orlando, Orlando
Moffitt Cancer Center, Tampa
KentuckyUniversity of Kentucky Markey Cancer Center, Lexington
LouisianaEast Jefferson General Hospital, Metairie
MassachusettsDana-Farber Cancer Institute, Boston
MichiganHenry Ford Cancer- Detroit, Detroit
The Cancer and Hematology Centers, Grand Rapids
MinnesotaMayo Clinic, Rochester
MissouriSiteman Cancer Center, St Louis
NebraskaUniversity of Nebraska Medical Center, Omaha
New MexicoUniversity of New Mexico Comprehensive Cancer Center, Albuquerque
New YorkRoswell Park Cancer Institute, Buffalo
Icahan School of Medicine at Mount Sinai, New York
University of Rochester Medical Center, Rochester
North CarolinaUniversity of North Carolina at Chapel Hill, Chapel Hill
Duke University Medical Center, Durham
North DakotaSanford Roger Maris Cancer Center, Fargo
OhioUniversity Hospitals Cleveland Medical Center, Cleveland
The Ohio State University Comprehensive Cancer Center, Columbus
OregonOregon Health and Science University, Portland
PennsylvaniaUniversity of Pennsylvania, Philadelphia
University of Pittsburgh Medical Center (UPMC) Hillman Cancer Center, Pittsburgh
TennesseeUniversity of Tennessee Medical Center, Knoxville
Henry-Joyce Cancer Clinic, Nashville
TexasTexas Oncology- Baylor Charles A. Sammons Cancer Center, Dallas
UtahHuntsman Cancer Institute, University of Utah, Salt Lake City
VirginiaUniversity of Virginia, Charlottesville
Virginia Cancer Specialists - Fairfax Office, Fairfax
WashingtonFred Hutchinson Cancer Center, Seattle
WisconsinFroedtert Hospital and the Medical College of Wisconsin, Milwaukee

Conditions

From ClinicalTrials.gov, data retrieved Sep 30, 2026. Each study sets its own eligibility; the study team decides who can join.