Pancreatic Neuroendocrine Tumor (pNET)Phase 2/3STELLAR-311NCT06943755
Zanzalintinib Versus Everolimus in Participants With Locally Advanced or Metastatic Neuroendocrine Tumors
A Phase 2/3 study testing Zanzalintinib and Everolimus in people with Pancreatic Neuroendocrine Tumor (pNET) and Extra-Pancreatic Neuroendocrine Tumor (epNET), run by Exelixis at 133 sites in 17 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pancreatic Neuroendocrine Tumor (pNET), Extra-Pancreatic Neuroendocrine Tumor (epNET)
- What is being tested?
- Zanzalintinib and Everolimus
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 440 participants
- Where
- 133 sitesin 17 countries
- Study dates
- 21 Jul 2025to 30 Jun 2029
- Phase
- Phase 2/3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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 locations and contacts
133 sites in 17 countries. Contact the study team or a site near you to ask about taking part.
Backup or International contact
133 sites in 17 countries
United States41 sites, 41 recruiting
- Recruiting
University of New Mexico Comprehensive Cancer Center
Albuquerque, New Mexico, 87131
- Recruiting
National Institute of Health
Bethesda, Maryland, 20892
- Recruiting
Cedars-Sinai Medical Center
Beverly Hills, California, 90211
- Recruiting
The University of Alabama at Birmingham
Birmingham, Alabama, 35294
- Recruiting
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
- Recruiting
Roswell Park Cancer Institute
Buffalo, New York, 14263
- Recruiting
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, 27599
- Recruiting
University of Virginia
Charlottesville, Virginia, 22903
- Recruiting
University Hospitals Cleveland Medical Center
Cleveland, Ohio, 44106
- Recruiting
The Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43221
- Recruiting
Texas Oncology- Baylor Charles A. Sammons Cancer Center
Dallas, Texas, 75264
- Recruiting
Henry Ford Cancer- Detroit
Detroit, Michigan, 48202
- Recruiting
Duke University Medical Center
Durham, North Carolina, 27710
- Recruiting
Virginia Cancer Specialists - Fairfax Office
Fairfax, Virginia, 22031
- Recruiting
Sanford Roger Maris Cancer Center
Fargo, North Dakota, 58102
- Recruiting
The Cancer and Hematology Centers
Grand Rapids, Michigan, 49546
- Recruiting
Mayo Clinic - Florida
Jacksonville, Florida, 32224
- Recruiting
University of Tennessee Medical Center
Knoxville, Tennessee, 37920
- Recruiting
University of Kentucky Markey Cancer Center
Lexington, Kentucky, 40536
- Recruiting
Norris Comprehensive Cancer Center
Los Angeles, California, 90033
- Recruiting
East Jefferson General Hospital
Metairie, Louisiana, 70006
- Recruiting
Froedtert Hospital and the Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
- Recruiting
Henry-Joyce Cancer Clinic
Nashville, Tennessee, 37232
- Recruiting
Icahan School of Medicine at Mount Sinai
New York, New York, 10029
- Recruiting
University of Nebraska Medical Center
Omaha, Nebraska, 68198
- Recruiting
AdventHealth Orlando
Orlando, Florida, 32804
- Recruiting
Stanford Cancer Center
Palo Alto, California, 94305
- Recruiting
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
- Recruiting
Mayo Clinic Hospital
Phoenix, Arizona, 85054
- Recruiting
University of Pittsburgh Medical Center (UPMC) Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232
- Recruiting
Oregon Health and Science University
Portland, Oregon, 97210
- Recruiting
Mayo Clinic
Rochester, Minnesota, 55905
- Recruiting
University of Rochester Medical Center
Rochester, New York, 14642
- Recruiting
Huntsman Cancer Institute, University of Utah
Salt Lake City, Utah, 84112
- Recruiting
UCLA Health - Santa Monica Cancer Care
Santa Monica, California, 90404
- Recruiting
Fred Hutchinson Cancer Center
Seattle, Washington, 98109
- Recruiting
Siteman Cancer Center
St Louis, Missouri, 63110
- Recruiting
Moffitt Cancer Center
Tampa, Florida, 33612
- Recruiting
The University of Arizona Cancer Center
Tucson, Arizona, 85724
- Recruiting
Kaiser Permanente Medical Center
Vallejo, California, 94589
- Recruiting
Georgetown University
Washington D.C., District of Columbia, 20007
Spain14 sites, 14 recruiting
- Recruiting
Institut Catalá d'Oncologia- ICO L'Hospitalet
Barcelona, 08908
- Recruiting
Hospital Universitario Vall D'Hebron
Barcelona, 8029
- Recruiting
Hospital General Universitario Gregorio Marañón
Madrid, 28007
- Recruiting
MD Anderson Cancer Center
Madrid, 28033
- Recruiting
Hospital Universitario Ramón y Cajal
Madrid, 28034
- Recruiting
Hospital Universitario 12 de Octubre
Madrid, 28041
- Recruiting
Hospital Universitario La Paz
Madrid, 28046
- Recruiting
Hospital General Universitario J.M Morales Meseguer
Murcia, 30008
- Recruiting
Hospital Universitario Central de Asturias
Oviedo, 33011
- Recruiting
Hospital Universitario Marqués de Valdecilla
Santander, 39008
- Recruiting
Hospital Clínico Universitario de Santiago de Compostela
Santiago de Compostela, 15706
- Recruiting
Hospital Universitario Vigen Del Rocío
Seville, 41013
- Recruiting
Hospital Universitario y Politécnico La Fe
Valencia, 46026
- Recruiting
Hospital Universitario Miguel Servet
Zaragoza, 50009
France11 sites, 11 recruiting
- Recruiting
Centre Hospitalier Universitaire de Caen Normandie
Caen, 14033
- Recruiting
CHU Beaujon
Clichy, 92110
- Recruiting
Centre Hospitalier Universitaire (CHU) de Lille - Hôpital Claude Huriez
Lille, 59037
- Recruiting
Hospices Civils de Lyon
Lyon, 69003
- Recruiting
Hôpital Timone
Marseille, 13005
- Recruiting
CHU de Montpellier Hôpital Saint Eloi
Montpellier, 34295
- Recruiting
Centre Hospitalier Universitaire Nantes
Nantes, 44093
- Recruiting
Centre Eugéne Marquis
Rennes, 35042
- Recruiting
CHRU Strasbourg Hôpital Hautepierre
Strasbourg, 67200
- Recruiting
Centre Hospitalier Universitaire (CHU) Toulouse
Toulouse, 31059
- Recruiting
Gustave Roussy
Villejuif, 94800
Italy11 sites, 11 recruiting
- Recruiting
Centro Di Riferimento Oncologico (CRO) Di Aviano
Aviano, 33081
- Recruiting
Azienda Ospedaliero-Universitaria Di Bologna IRCCS Istituto Di Ricerca E Di Cura A Carattere Scientifico
Bologna, 40138
- Recruiting
Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori IRST s.r.l.
Meldola, 47014
- Recruiting
Humanitas Mirasole S.p.A.
Milan, 20089
- Recruiting
Fondazione IRCCS Istituto Nazionale Tumori
Milan, 20133
- Recruiting
Instituto Europeo di Oncologia
Milan, 20141
- Recruiting
Istituto Nazionale Tumori IRCCS - Fondazione Pascale
Naples, 80131
- Recruiting
Azienda Ospedaliero-Universitaria San Luigi Gonzaga
Orbassano to, 10043
- Recruiting
Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone
Palermo, 90127
- Recruiting
Azienda Ospedaliero-Universitaria Policlinico Umberto I
Roma, 00161
- Recruiting
Azienda Ospedaliero-Universitaria Sant'Andrea
Roma, 00189
United Kingdom10 sites, 10 recruiting
- Recruiting
University Hospitals Birmingham NHS Foundation Trust
Birmingham, B15 2GW
- Recruiting
Velindre Cancer Center
Cardiff, CF14 2TL
- Recruiting
NHS Greater Glasgow and Clyde
Glasgow, G12 0YN
- Recruiting
The Clatterbridge Cancer Centre
Liverpool, L7 8YA
- Recruiting
Guy's and St Thomas' NHS Foundation Trust
London, SE1 9RT
- Recruiting
King's College Hospital NHS Foundation Trust
London, SE5 9RS
- Recruiting
Oxford University Hospitals NHS Foundation Trust
Oxford, OX3 7LE
- Recruiting
Sheffield Teaching Hospitals NHS Foundation Trust
Sheffield, S10 2SJ
- Recruiting
The Royal Marsden NHS Foundation Trust
Sutton, SM2 5PT
- Recruiting
Swansea Bay University Health Board
Swansea, SA2 8QA
Germany7 sites, 7 recruiting
- Recruiting
Evangelische Lungenklinik
Berlin, 13125
- Recruiting
Universitätsklinik Erlangen
Erlangen, 91054
- Recruiting
ENETS Center of Excellence, University Hospital Essen
Essen, 45157
- Recruiting
Universitätsmedizin Mainz der Johannes Gutenberg-Universität Mainz
Mainz, 44131
- Recruiting
Universitätsklinikum Gießen und Marburg GmbH, Standort Marburg
Marburg, 35043
- Recruiting
Universitätsklinikum Tübingen
Tübingen, 72076
- Recruiting
University Hospital Würzburg
Würzburg, 97080
Australia6 sites, 6 recruiting
- Recruiting
Monash Health
Clayton, 3168
- Recruiting
Royal Brisbane and Women's Hospital
Herston, 4029
- Recruiting
Peter MacCallum Cancer Centre
Melbourne, 3000
- Recruiting
Fiona Stanley Hospital
Murdoch, 6150
- Recruiting
GenesisCare North Shore
St Leonards, 2065
- Recruiting
The Queen Elizabeth Hospital
Woodville South, 5011
Poland5 sites, 5 recruiting
- Recruiting
Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie - Państwowy Instytut Badawczy, Oddział w Gliwicach
Gliwice, 44-102
- Recruiting
Śląskiego Uniwersytet Medyczny w Katowicach
Katowice, 40-514
- Recruiting
Samodzielny Publiczny Zakład Opieki Zdrowotnej Szpital Uniwesytecki w Krakowie
Krakow, 30-688
- Recruiting
Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie - Państwowy Instytut Badawczy
Warsaw, 02-034
- Recruiting
FutureMeds Wrocław
Wroclaw, 53-673
South Korea5 sites, 5 recruiting
- Recruiting
Korea University Anam Hospital
Seoul, 2841
- Recruiting
Seoul National University Hospital
Seoul, 3080
- Recruiting
Severence Hospital, Yonsei University Health System
Seoul, 3722
- Recruiting
Asan Medical Center
Seoul, 5505
- Recruiting
Samsung Medical Center
Seoul, 6351
Belgium4 sites, 4 recruiting
- Recruiting
Institut Jules Bordet
Brussels, 1070
- Recruiting
Universitair Ziekenhuis Antwerpen (UZA)
Edegem, 2650
- Recruiting
UZ Leuven
Leuven, 3000
- Recruiting
Cliniques Universitaires Saint-Luc (UCLouvain)
Woluwe-Saint-Lambert, 1200
Netherlands4 sites, 4 recruiting
- Recruiting
Het Netherlands Kanker Institut (NKI)/ Antoni van Leeuwenhoek
Amsterdam, 1066 CX
- Recruiting
Amsterdam UMC
Amsterdam, 1081 HV
- Recruiting
Maastricht Universitair Medisch Centrum
Maastricht, 6229 HX
- Recruiting
Maxima Medisch Centrum
Veldhoven, 5504 DB
Austria3 sites, 3 recruiting
- Recruiting
Medical University of Graz
Graz, 8036
- Recruiting
Paracelsus Medical University Hospital Salzburg
Salzburg, 5020
- Recruiting
Medical University of Vienna
Vienna, 1090
Canada3 sites, 3 recruiting
- Recruiting
Verspeeten Family Cancer Center - London Health Sciences Centre
London, N6A 5W9
- Recruiting
The Ottawa Hospital Cancer Center
Ottawa, K1H 8L6
- Recruiting
Sunnybrook Health Sciences Centre
Toronto, M4N 3M5
China3 sites, 3 recruiting
- Recruiting
Humanity and Health Clinical Trial Centre
Hong Kong
- Recruiting
Prince of Wales Hospital
Hong Kong
- Recruiting
Queen Mary Hospital
Hong Kong
Taiwan3 sites, 3 recruiting
- Recruiting
National Cheng Kung University Hospital
Tainan, 704
- Recruiting
Taipei Veterans General Hospital
Taipei, 112
- Recruiting
Linkou Chang Gung Memorial Hospital
Taoyuan, 333
Puerto Rico2 sites, 1 recruiting
- Recruiting
Pan American Center for Oncology Trials, LLC
San Juan, 00909
- Withdrawn
FDI Clinical Research
San Juan, 00927
Brazil1 site, 1 recruiting
- Recruiting
Associação Hospitalar Moinhos de Vento
Porto Alegre, 90560-032
About this study
Official title: 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.
- Being tested
- Zanzalintinib, Everolimus
- Keywords
- Metastatic Cancer, Locally Advanced Cancer, Neuroendocrine Tumor (NET)
- Medical subject headings
- Adenoma, Islet Cell, Neoplasm Metastasis, Neuroendocrine Tumors
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ZanzalintinibDrug
Also called XL092
Administered as specified in the treatment arm.
EverolimusDrug
Also called Afinitor
Administered as specified in the treatment arm.
| Study group | Role | What they receive |
|---|---|---|
| Everolimus | Active comparator | Participants will receive everolimus oral tablets once daily. Receives: Drug: Everolimus |
| Zanzalintinib | Experimental | Participants will receive zanzalintinib oral tablets once daily. Receives: Drug: Zanzalintinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version (RECIST) 1.1 as Assessed by Blinded Independent Central Review (BICR)
Measured: Up to 48 months
Secondary outcomes (8)
PFS Per RECIST 1.1 as Assessed by Investigator
Measured: Up to 48 months
Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by BICR and Investigator
Measured: Up to 48 months
Overall Survival (OS)
Measured: Up to 60 months
Duration of Response (DOR) Per RECIST 1.1 as Assessed by BICR and Investigator
Measured: Up to 48 months
Disease Control Rate (DCR) Per RECIST 1.1 as Assessed by BICR and Investigator
Measured: 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
Measured: 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
Measured: Up to 48 months
Number of Participants With Adverse Events
Measured: Up to 48 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Apr 2025
- Study start21 Jul 2025
- Primary completion30 Jun 2029 (estimated)
- Study completion30 Jun 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Pancreatic Neuroendocrine Tumor (pNET)Studies of the same condition, open and under way.
- More trials run by ExelixisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 440 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Exelixis
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Exelixis
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06943755
- Sponsor's protocol ID
- XL092-311
- Other IDs
- 2025-521043-20-00, 1011801, 2025
- Acronym
- STELLAR-311
- Status last verified
- Oct 2026
- First submitted
- 17 Apr 2025
- Last updated
- 23 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Chan JA, Strosberg JR, Yoo C, Singh S, Huang H, Goel M, Scheffold C, Capdevila J. STELLAR-311: a randomized phase II/III study of zanzalintinib versus everolimus in advanced neuroendocrine tumors. Future Oncol. 2026 Sep 28:1-8. doi: 10.1080/14796694.2026.2733790. Online ahead of print.
PubMed 42803451