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

August 25, 2026 updated by: Exelixis

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

440

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Exelixis Clinical Trials
  • Phone Number: 1-888-EXELIXIS (888-393-5494)
  • Email: druginfo@exelixis.com

Study Contact Backup

  • Name: Backup or International
  • Phone Number: 650-837-7400

Study Locations

  • Australia
      • Clayton, Australia, 3168
        • Recruiting
        • Monash Health
      • Herston, Australia, 4029
        • Recruiting
        • Royal Brisbane and Women's Hospital
      • Melbourne, Australia, 3000
        • Recruiting
        • Peter MacCallum Cancer Centre
      • Murdoch, Australia, 6150
        • Recruiting
        • Fiona Stanley Hospital
      • St Leonards, Australia, 2065
        • Recruiting
        • GenesisCare North Shore
      • Woodville South, Australia, 5011
        • Recruiting
        • The Queen Elizabeth Hospital
  • Austria
      • Graz, Austria, 8036
        • Recruiting
        • Medical University of Graz
      • Salzburg, Austria, 5020
        • Recruiting
        • Paracelsus Medical University Hospital Salzburg
      • Vienna, Austria, 1090
        • Recruiting
        • Medical University of Vienna
  • Belgium
      • Brussels, Belgium, 1070
        • Recruiting
        • Institut Jules Bordet
      • Leuven, Belgium, 3000
        • Recruiting
        • UZ Leuven
      • Woluwe-Saint-Lambert, Belgium, 1200
        • Recruiting
        • Cliniques Universitaires Saint-Luc (UCLouvain)
  • Brazil
      • Porto Alegre, Brazil, 90560-032
        • Recruiting
        • Associação Hospitalar Moinhos de Vento
  • Canada
      • London, Canada, N6A 5W9
        • Recruiting
        • Verspeeten Family Cancer Center - London Health Sciences Centre
      • Ottawa, Canada, K1H 8L6
        • Recruiting
        • The Ottawa Hospital Cancer Center
      • Toronto, Canada, M4N 3M5
        • Recruiting
        • Sunnybrook Health Sciences Centre
  • China
      • Hong Kong, China
        • Recruiting
        • Queen Mary Hospital
      • Hong Kong, China
        • Recruiting
        • Prince of Wales Hospital
      • Hong Kong, China
        • Recruiting
        • Humanity and Health Clinical Trial Centre
  • France
      • Caen, France, 14033
        • Recruiting
        • Centre Hospitalier Universitaire de Caen Normandie
      • Clichy, France, 92110
        • Recruiting
        • CHU Beaujon
      • Lille, France, 59037
        • Recruiting
        • Centre Hospitalier Universitaire (CHU) de Lille - Hôpital Claude Huriez
      • Lyon, France, 69003
        • Recruiting
        • Hospices Civils de Lyon
      • Marseille, France, 13005
        • Recruiting
        • Hôpital Timone
      • Montpellier, France, 34295
        • Recruiting
        • CHU de Montpellier Hopital Saint Eloi
      • Nantes, France, 44093
        • Recruiting
        • Centre Hospitalier Universitaire Nantes
      • Rennes, France, 35042
        • Recruiting
        • Centre Eugène Marquis
      • Strasbourg, France, 67200
        • Recruiting
        • CHRU Strasbourg Hôpital Hautepierre
      • Toulouse, France, 31059
        • Recruiting
        • Centre Hospitalier Universitaire (CHU) Toulouse
      • Villejuif, France, 94800
        • Recruiting
        • Gustave Roussy
  • Germany
      • Berlin, Germany, 13125
        • Recruiting
        • Evangelische Lungenklinik
      • Erlangen, Germany, 91054
        • Recruiting
        • Universitätsklinik Erlangen
      • Essen, Germany, 45157
        • Recruiting
        • ENETS Center of Excellence, University Hospital Essen
      • Marburg, Germany, 35043
        • Recruiting
        • Universitätsklinikum Gießen und Marburg GmbH, Standort Marburg
      • Tübingen, Germany, 72076
        • Recruiting
        • Universitätsklinikum Tübingen
      • Würzburg, Germany, 97080
        • Recruiting
        • University Hospital Würzburg
  • Italy
      • Bologna, Italy, 40138
        • Recruiting
        • Azienda Ospedaliero-Universitaria Di Bologna IRCCS Istituto Di Ricerca E Di Cura A Carattere Scientifico
      • Meldola, Italy, 47014
        • Recruiting
        • Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori IRST s.r.l.
      • Milan, Italy, 20133
        • Recruiting
        • Fondazione IRCCS Istituto Nazionale Tumori
      • Milan, Italy, 20141
        • Recruiting
        • Instituto Europeo di Oncologia
      • Milan, Italy, 20089
        • Recruiting
        • Humanitas Mirasole S.p.A.
      • Naples, Italy, 80131
        • Recruiting
        • Istituto Nazionale Tumori IRCCS - Fondazione Pascale
      • Orbassano to, Italy, 10043
        • Recruiting
        • Azienda Ospedaliero-Universitaria San Luigi Gonzaga
      • Palermo, Italy, 90127
        • Recruiting
        • Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone
      • Roma, Italy, 00189
        • Recruiting
        • Azienda Ospedaliero-Universitaria Sant'Andrea
      • Roma, Italy, 00161
        • Recruiting
        • Azienda Ospedaliero-Universitaria Policlinico Umberto I
  • Netherlands
      • Amsterdam, Netherlands, 1081 HV
        • Recruiting
        • Amsterdam UMC
      • Amsterdam, Netherlands, 1066 CX
        • Recruiting
        • Het Netherlands Kanker Institut (NKI)/ Antoni van Leeuwenhoek
      • Maastricht, Netherlands, 6229 HX
        • Recruiting
        • Maastricht Universitair Medisch Centrum
      • Veldhoven, Netherlands, 5504 DB
        • Recruiting
        • Maxima Medisch Centrum
  • Poland
      • Gliwice, Poland, 44-102
        • Recruiting
        • Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie - Państwowy Instytut Badawczy, Oddział w Gliwicach
      • Katowice, Poland, 40-514
        • Recruiting
        • Śląskiego Uniwersytet Medyczny w Katowicach
      • Krakow, Poland, 30-688
        • Recruiting
        • Samodzielny Publiczny Zakład Opieki Zdrowotnej Szpital Uniwesytecki w Krakowie
      • Warsaw, Poland, 02-034
        • Recruiting
        • Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie - Państwowy Instytut Badawczy
      • Wroclaw, Poland, 53-673
        • Recruiting
        • FutureMeds Wrocław
  • Puerto Rico
      • San Juan, Puerto Rico, 00909
        • Recruiting
        • Pan American Center for Oncology Trials, LLC
      • San Juan, Puerto Rico, 00927
        • Withdrawn
        • FDI Clinical Resesarch
  • South Korea
      • Seoul, South Korea, 6351
        • Recruiting
        • Samsung Medical Center
      • Seoul, South Korea, 5505
        • Recruiting
        • Asan Medical Center
      • Seoul, South Korea, 3080
        • Recruiting
        • Seoul National University Hospital
      • Seoul, South Korea, 2841
        • Recruiting
        • Korea University Anam Hospital
      • Seoul, South Korea, 3722
        • Recruiting
        • Severence Hospital, Yonsei University Health System
  • Spain
      • Barcelona, Spain, 8029
        • Recruiting
        • Hospital Universitario Vall d'Hebron
      • Madrid, Spain, 28034
        • Recruiting
        • Hospital Universitario Ramon Y Cajal
      • Madrid, Spain, 28041
        • Recruiting
        • Hospital Universitario 12 de Octubre
      • Madrid, Spain, 28046
        • Recruiting
        • Hospital Universitario La Paz
      • Madrid, Spain, 28007
        • Recruiting
        • Hospital General Universitario Gregorio Maranon
      • Murcia, Spain, 30008
        • Recruiting
        • Hospital General Universitario J.M Morales Meseguer
      • Oviedo, Spain, 33011
        • Recruiting
        • Hospital Universitario Central de Asturias
      • Santander, Spain, 39008
        • Recruiting
        • Hospital Universitario Marques de Valdecilla
      • Santiago de Compostela, Spain, 15706
        • Recruiting
        • Hospital Clinico Universitario de Santiago de Compostela
      • Seville, Spain, 41013
        • Recruiting
        • Hospital Universitario Vigen Del Rocío
      • Valencia, Spain, 46026
        • Recruiting
        • Hospital Universitario Y Politecnico La Fe
      • Zaragoza, Spain, 50009
        • Recruiting
        • Hospital Universitario Miguel Servet
  • United Kingdom
      • Birmingham, United Kingdom, B15 2GW
        • Recruiting
        • University Hospitals Birmingham Nhs Foundation Trust
      • Cardiff, United Kingdom, CF14 2TL
        • Recruiting
        • Velindre Cancer Center
      • Glasgow, United Kingdom, G12 0YN
        • Recruiting
        • NHS Greater Glasgow and Clyde
      • Liverpool, United Kingdom, L7 8YA
        • Recruiting
        • The Clatterbridge Cancer Centre
      • London, United Kingdom, SE5 9RS
        • Recruiting
        • King's College Hospital NHS Foundation Trust
      • London, United Kingdom, SE1 9RT
        • Recruiting
        • Guy's and St Thomas' NHS Foundation Trust
      • Oxford, United Kingdom, OX3 7LE
        • Recruiting
        • Oxford University Hospitals NHS Foundation Trust
      • Sheffield, United Kingdom, S10 2SJ
        • Recruiting
        • Sheffield Teaching Hospitals NHS Foundation Trust
      • Sutton, United Kingdom, SM2 5PT
        • Recruiting
        • The Royal Marsden NHS Foundation Trust
      • Swansea, United Kingdom, SA2 8QA
        • Recruiting
        • Swansea Bay University Health Board
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35294
        • Recruiting
        • The University of Alabama at Birmingham
    • Arizona
      • Phoenix, Arizona, United States, 85054
        • Recruiting
        • Mayo Clinic Hospital
      • Tucson, Arizona, United States, 85724
        • Recruiting
        • The University of Arizona Cancer Center
    • California
      • Beverly Hills, California, United States, 90211
        • Recruiting
        • Cedars-Sinai Medical Center
      • Los Angeles, California, United States, 90033
        • Recruiting
        • Norris Comprehensive Cancer Center
      • Palo Alto, California, United States, 94305
        • Recruiting
        • Stanford Cancer Center
      • Santa Monica, California, United States, 90404
        • Recruiting
        • UCLA Health - Santa Monica Cancer Care
      • Vallejo, California, United States, 94589
        • Recruiting
        • Kaiser Permanente Medical Center
    • District of Columbia
      • Washington D.C., District of Columbia, United States, 20007
        • Recruiting
        • Georgetown University
    • Florida
      • Jacksonville, Florida, United States, 32224
        • Recruiting
        • Mayo Clinic - Florida
      • Orlando, Florida, United States, 32804
        • Recruiting
        • AdventHealth Orlando
      • Tampa, Florida, United States, 33612
        • Recruiting
        • Moffitt Cancer Center
    • Kentucky
      • Lexington, Kentucky, United States, 40536
        • Recruiting
        • University of Kentucky Markey Cancer Center
    • Louisiana
      • Metairie, Louisiana, United States, 70006
        • Recruiting
        • East Jefferson General Hospital
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Recruiting
        • Dana-Farber Cancer Institute
    • Michigan
      • Detroit, Michigan, United States, 48202
        • Recruiting
        • Henry Ford Cancer- Detroit
      • Grand Rapids, Michigan, United States, 49546
        • Recruiting
        • The Cancer and Hematology Centers
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Recruiting
        • Mayo Clinic
    • Missouri
      • St Louis, Missouri, United States, 63110
        • Recruiting
        • Siteman Cancer Center
    • Nebraska
      • Omaha, Nebraska, United States, 68198
        • Recruiting
        • University Of Nebraska Medical Center
    • New Mexico
      • Albuquerque, New Mexico, United States, 87131
        • Recruiting
        • University of New Mexico Comprehensive Cancer Center
    • New York
      • Buffalo, New York, United States, 14263
        • Recruiting
        • Roswell Park Cancer Institute
      • New York, New York, United States, 10029
        • Recruiting
        • Icahan School of Medicine at Mount Sinai
      • Rochester, New York, United States, 14642
        • Recruiting
        • University of Rochester Medical Center
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599
        • Recruiting
        • University of North Carolina at Chapel Hill
      • Durham, North Carolina, United States, 27710
        • Recruiting
        • Duke University Medical Center
    • North Dakota
      • Fargo, North Dakota, United States, 58102
        • Recruiting
        • Sanford Roger Maris Cancer Center
    • Ohio
      • Cleveland, Ohio, United States, 44106
        • Recruiting
        • University Hospitals Cleveland Medical Center
      • Columbus, Ohio, United States, 43221
        • Recruiting
        • The Ohio State University Comprehensive Cancer Center
    • Oregon
      • Portland, Oregon, United States, 97210
        • Recruiting
        • Oregon Health and Science University
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Recruiting
        • University of Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15232
        • Recruiting
        • University of Pittsburgh Medical Center (UPMC) Hillman Cancer Center
    • Tennessee
      • Knoxville, Tennessee, United States, 37920
        • Recruiting
        • University of Tennessee Medical Center
      • Nashville, Tennessee, United States, 37232
        • Recruiting
        • Henry-Joyce Cancer Clinic
    • Texas
      • Dallas, Texas, United States, 75264
        • Recruiting
        • Texas Oncology- Baylor Charles A. Sammons Cancer Center
    • Utah
      • Salt Lake City, Utah, United States, 84112
        • Recruiting
        • Huntsman Cancer Institute, University of Utah
    • Virginia
      • Charlottesville, Virginia, United States, 22903
        • Recruiting
        • University of Virginia
      • Fairfax, Virginia, United States, 22031
        • Recruiting
        • Virginia Cancer Specialists - Fairfax Office
    • Washington
      • Seattle, Washington, United States, 98109
        • Recruiting
        • Fred Hutchinson Cancer Center
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53226
        • Recruiting
        • Froedtert Hospital and the Medical College of Wisconsin

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Zanzalintinib
Participants will receive zanzalintinib oral tablets once daily.
Drug: Zanzalintinib
Administered as specified in the treatment arm.
Other Names:
  • XL092
Active Comparator: Everolimus
Participants will receive everolimus oral tablets once daily.
Drug: Everolimus
Administered as specified in the treatment arm.
Other Names:
  • Afinitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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
Up to 48 months

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Exelixis

Investigators

  • Study Director: Medical Director, Exelixis

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 21, 2025

Primary Completion (Estimated)

June 30, 2029

Study Completion (Estimated)

June 30, 2029

Study Registration Dates

First Submitted

April 17, 2025

First Submitted That Met QC Criteria

April 17, 2025

First Posted (Actual)

April 24, 2025

Study Record Updates

Last Update Posted (Actual)

August 26, 2026

Last Update Submitted That Met QC Criteria

August 25, 2026

Last Verified

August 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • XL092-311
  • 2025 (U.S. NIH Grant/Contract: Faculty of Social Sciences Scientific Grant at the University of Gdańsk)
  • 2025-521043-20-00 (Ctis)
  • 1011801 (Other Identifier: IRAS)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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