Home › Trials › NCT06943755

Zanzalintinib versus everolimus for advanced or metastatic pancreatic and extra‑pancreatic neuroendocrine tumors

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

Phase2; Phase3 Interventional Exelixis · NCT06943755

This trial tests whether zanzalintinib works better than everolimus for people with previously treated, unresectable or metastatic pancreatic or extra‑pancreatic neuroendocrine tumors.

Quick facts

PhasePhase2; Phase3
Study typeInterventional
Enrollment440 (estimated)
Ages18 Years and up
SexAll
SponsorExelixis Industry-sponsored
Drugs / interventionschemotherapy, Radiation, zanzalintinib
Locations80 sites (Birmingham, Alabama and 79 other locations)
Trial IDNCT06943755 on ClinicalTrials.gov

What this trial studies

Adults with well‑differentiated Grade 1–3 pancreatic or extra‑pancreatic neuroendocrine tumors that have progressed after prior therapy will be enrolled. Participants must have measurable disease by RECIST 1.1 and documented radiographic progression within 12 months, and tumor tissue (archival or fresh biopsy) is required when feasible. Enrolled participants will receive either zanzalintinib or everolimus and will be followed with imaging and clinical assessments to compare outcomes between the two treatments. The trial spans phase 2/3 to determine whether the newer agent provides improved disease control compared with the established mTOR inhibitor.

Who should consider this trial

Good fit: Ideal candidates are adults with histologically confirmed, well‑differentiated Grade 1–3 pancreatic or extra‑pancreatic NETs that are unresectable or metastatic, previously treated, measurable by RECIST 1.1, and with documented radiographic progression within the prior 12 months who can provide tumor tissue.

Not a fit: Patients with high‑grade neuroendocrine carcinomas or other excluded tumor types (such as medullary thyroid cancer, pheochromocytoma/paraganglioma, or Merkel cell carcinoma) are not eligible and are unlikely to benefit from this comparison.

Why it matters

Potential benefit: If successful, zanzalintinib could provide better disease control or longer progression‑free survival than everolimus for people with advanced NETs.

How similar studies have performed: Everolimus, an mTOR inhibitor, is an established treatment option for some NETs, while zanzalintinib is a newer targeted agent with limited prior clinical data in this setting.

Eligibility criteria

Show full inclusion / exclusion 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.

Where this trial is running

Birmingham, Alabama and 79 other locations

+30 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Pancreatic Neuroendocrine TumorExtra-Pancreatic Neuroendocrine TumorMetastatic CancerLocally Advanced CancerNeuroendocrine Tumor
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.