Clinical trial NCT06943755: Zanzalintinib Versus Everolimus in Participants With Locally Advanced or Metastatic Neuroendocrine Tumors
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
PHASE3
Conditions: Pancreatic Neuroendocrine Tumor (pNET)
Extra-Pancreatic Neuroendocrine Tumor (epNET)
Keywords: Metastatic Cancer
Locally Advanced Cancer
Neuroendocrine Tumor (NET)
Lead sponsor: Exelixis
Sponsor class: INDUSTRY
First posted: 2025-04-24
Enrollment: 440
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version (RECIST) 1.1 as Assessed by Blinded Independent Central Review (BICR)
timeFrame: Up to 48 months
Secondary outcomes:
measure: PFS Per RECIST 1.1 as Assessed by Investigator
timeFrame: Up to 48 months
measure: Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by BICR and Investigator
timeFrame: Up to 48 months
measure: Overall Survival (OS)
timeFrame: Up to 60 months
measure: Duration of Response (DOR) Per RECIST 1.1 as Assessed by BICR and Investigator
timeFrame: Up to 48 months
measure: Disease Control Rate (DCR) Per RECIST 1.1 as Assessed by BICR and Investigator
timeFrame: Up to 48 months
measure: 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
timeFrame: Up to 48 months
measure: Change From Baseline in Participant-Reported GHS and Disease-Related Symptoms as Assessed by EORTC Gastrointestinal Neuroendocrine Tumor module (QLQ-GI.NET21) Score
timeFrame: Up to 48 months
measure: Number of Participants With Adverse Events
timeFrame: Up to 48 months
Other outcomes:
Locations:
city: Grand Rapids
country: United States
facility: Exelixis Clinical Site #1
state: Michigan
Study officials:
affiliation: Exelixis
name: Medical Director
role: STUDY_DIRECTOR
References: