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

NCT06943755 | Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: XL092-3112025-521043-20-001011801
• Study Type: interventional
• Target: 440
• Locations: 12 countries
• Sites: 79

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)

Keywords

Metastatic Cancer; Locally Advanced Cancer; Neuroendocrine Tumor (NET)

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version (RECIST) 1.1 as Assessed by Blinded Independent Central Review (BICR)

  Up to 48 months

Secondary Outcomes (8)

• PFS Per RECIST 1.1 as Assessed by Investigator

  Up to 48 months

• Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by BICR and Investigator

  Up to 48 months

• Overall Survival (OS)

  Up to 60 months

• Duration of Response (DOR) Per RECIST 1.1 as Assessed by BICR and Investigator

  Up to 48 months

• Disease Control Rate (DCR) Per RECIST 1.1 as Assessed by BICR and Investigator

  Up to 48 months

Study Arms (2)

Zanzalintinib

EXPERIMENTAL

Participants will receive zanzalintinib oral tablets once daily.

Drug: Zanzalintinib

Everolimus

ACTIVE COMPARATOR

Participants will receive everolimus oral tablets once daily.

Drug: Everolimus

Interventions

Zanzalintinib DRUG

Administered as specified in the treatment arm.

Also known as: XL092

Zanzalintinib

Everolimus DRUG

Administered as specified in the treatment arm.

Also known as: Afinitor

Everolimus

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Exelixis: lead

Study Sites (80)

Exelixis Clinical Site #43

Birmingham, Alabama, 35294, United States

RECRUITING

Exelixis Clinical Site #36

Phoenix, Arizona, 85054, United States

RECRUITING

Exelixis Clinical Site #42

Tucson, Arizona, 85724, United States

RECRUITING

Exelixis Clinical Site #18

Beverly Hills, California, 90211, United States

RECRUITING

Exelixis Clinical Site #16

Los Angeles, California, 90033, United States

RECRUITING

Exelixis Clinical Site #54

Palo Alto, California, 94305, United States

RECRUITING

Exelixis Clinical Site #12

Santa Monica, California, 90404, United States

RECRUITING

Exelixis Clinical Site #29

Vallejo, California, 94589, United States

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Exelixis Clinical Site #19

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

RECRUITING

Exelixis Clinical Site #35

Jacksonville, Florida, 32224, United States

RECRUITING

Exelixis Clinical Site #11

Tampa, Florida, 33612, United States

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Exelixis Clinical Site #9

Lexington, Kentucky, 40536, United States

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Exelixis Clinical Site #23

Metairie, Louisiana, 70006, United States

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Exelixis Clinical Site #8

Boston, Massachusetts, 02215, United States

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Exelixis Clinical Site #47

Detroit, Michigan, 48202, United States

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Exelixis Clinical Site #1

Grand Rapids, Michigan, 49546, United States

RECRUITING

Exelixis Clinical Site #38

Rochester, Minnesota, 55905, United States

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Exelixis Clinical Site #5

St Louis, Missouri, 63110, United States

RECRUITING

Exelixis Clinical Site #25

Omaha, Nebraska, 68198, United States

RECRUITING

Exelixis Clinical Site #14

Albuquerque, New Mexico, 87131, United States

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Exelixis Clinical Site #59

Buffalo, New York, 14263, United States

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Exelixis Clinical Site #7

New York, New York, 10029, United States

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Exelixis Clinical Site #53

Rochester, New York, 14642, United States

RECRUITING

Exelixis Clinical Site #17

Chapel Hill, North Carolina, 27599, United States

RECRUITING

Exelixis Clinical Site #6

Durham, North Carolina, 27710, United States

RECRUITING

Exelixis Clinical Site #57

Fargo, North Dakota, 58102, United States

RECRUITING

Exelixis Clinical Site #39

Cleveland, Ohio, 44106, United States

RECRUITING

Exelixis Clinical Site #28

Columbus, Ohio, 43221, United States

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Exelixis Clinical Site #27

Portland, Oregon, 97210, United States

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Exelixis Clinical Site #20

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

Exelixis Clinical Site #21

Pittsburgh, Pennsylvania, 15232, United States

RECRUITING

Exelixis Clinical Site #24

Knoxville, Tennessee, 37920, United States

RECRUITING

Exelixis Clinical Site #65

Nashville, Tennessee, 37232, United States

RECRUITING

Exelixis Clinical Site #10

Dallas, Texas, 75264, United States

RECRUITING

Exelixis Clinical Site #15

Salt Lake City, Utah, 84112, United States

RECRUITING

Exelixis Clinical Site #3

Charlottesville, Virginia, 22903, United States

RECRUITING

Exelixis Clinical Site #13

Fairfax, Virginia, 22031, United States

RECRUITING

Exelixis Clinical Site #34

Seattle, Washington, 98109, United States

RECRUITING

Exelixis Clinical Site #31

Milwaukee, Wisconsin, 53226, United States

RECRUITING

Exelixis Clinical Site #40

Saint Leonards, New South Wales, 2065, Australia

RECRUITING

Exelixis Clinical Site #67

Woodville South, South Australia, 5011, Australia

RECRUITING

Exelixis Clinical Site #51

Clayton, Victoria, 3168, Australia

RECRUITING

Exelixis Clinical Site #68

Clayton, Victoria, 3168, Australia

RECRUITING

Exelixis Clinical Site #55

Herston, 4029, Australia

RECRUITING

Exelixis Clinical Site #48

Graz, 8036, Austria

RECRUITING

Exelixis Clinical Site #61

Ottawa, K1H8L6, Canada

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Exelixis Clinical Site #49

Toronto, M4N3M5, Canada

RECRUITING

Exelixis Clinical Site #63

Hong Kong, China

RECRUITING

Exelixis Clinical Site 58

Berlin, 13125, Germany

RECRUITING

Exelixis Clinical Site #52

Tübingen, 72076, Germany

RECRUITING

Exelixis Clinical Site #75

Würzburg, 97080, Germany

RECRUITING

Exelixis Clinical Site #77

China, Hong Kong

RECRUITING

Exelixis Clinical Site #78

Naples, Naples, 80131, Italy

RECRUITING

Exelixis Clinical Site #70

Roma, 00185, Italy

RECRUITING

Exelixis Clinical Site #69

Warsaw, Masovian Voivodeship, 02-034, Poland

RECRUITING

Exelixis Clinical Site #45

Katowice, 40-514, Poland

RECRUITING

Exelixis Clinical Site #37

Warsaw, 53-673, Poland

RECRUITING

Exelixis Clinical Site #72

Gliwice, Ślaskie, 44-102, Poland

RECRUITING

Exelixis Clinical Site #2

San Juan, 00909, Puerto Rico

RECRUITING

Exelixis Clinical Site # 4

San Juan, 00927, Puerto Rico

WITHDRAWN

Exelixis Clinical Site #30

Seoul, 02841, South Korea

RECRUITING

Exelixis Clinical Site #46

Seoul, 03080, South Korea

RECRUITING

Exelixis Clinical Site #32

Seoul, 03722, South Korea

RECRUITING

Exelixis Clinical Site #41

Seoul, 05505, South Korea

RECRUITING

Exelixis Clinical Site #26

Seoul, 06351, South Korea

RECRUITING

Exelixis Clinical Site #74

Santiago de Compostela, A Coruña, 15706, Spain

RECRUITING

Exelixis Clinical Site #80

Oviedo, Principality of Asturias, 33011, Spain

RECRUITING

Exelixis Clinical Site #76

Barcelona, 08029, Spain

RECRUITING

Exelixis Clinical Site #56

Madrid, 28034, Spain

RECRUITING

Exelixis Clinical Site #73

Madrid, 28041, Spain

RECRUITING

Exelixis Clinical Site #44

Madrid, 28046, Spain

RECRUITING

Exelixis Clinical Site #66

Murcia, 30008, Spain

RECRUITING

Exelixis Clinical Site #60

Santander, 39008, Spain

RECRUITING

Exelixis Clinical Site #62

Seville, 41013, Spain

RECRUITING

Exelixis Clinical Site #64

Valencia, 46026, Spain

RECRUITING

Exelixis Clinical Site #79

Zaragoza, 50009, Spain

RECRUITING

Exelixis Clinical Site #22

London, England, SE5 9RS, United Kingdom

RECRUITING

Exelixis Clinical Site #71

Oxford, England, OX3 7LE, United Kingdom

RECRUITING

Exelixis Clinical Site #50

Liverpool, L7 8YA, United Kingdom

RECRUITING

Exelixis Clinical Site #33

Sheffield, S10 2SJ, United Kingdom

RECRUITING

MeSH Terms

Conditions

Adenoma, Islet Cell; Neoplasm Metastasis; Neuroendocrine Tumors

Interventions

Everolimus

Condition Hierarchy (Ancestors)

Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Pancreatic Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Study Officials

• Medical Director

  Exelixis

  STUDY DIRECTOR

Central Study Contacts

Exelixis Clinical Trials

CONTACT

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

Backup or International

CONTACT

650-837-7400

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 17, 2025
• First Posted: April 24, 2025
• Study Start: July 21, 2025
• Primary Completion (Estimated): June 1, 2029
• Study Completion (Estimated): June 1, 2029
• Last Updated: April 17, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

PL (4); US (39); CA (2); KR (5); GB (4); PR (2); IT (2); AU (5); DE (3); ES (11); CN (1); HK (1)