Zanzalintinib Maintenance in Patients With High Grade Neuroendocrine Neoplasms (HG-NENs)

NCT06926634 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 202506139
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 2

Brief Summary

The investigators hypothesize that zanzalintinib maintenance therapy after initial cytotoxic chemotherapy can prolong the progression-free survival (PFS) in patients with high-grade NENs.

Conditions

High Grade Neuroendocrine Neoplasms

Keywords

High grade; Neuroendocrine tumors; Zanzalintinib; Phase 2

Outcome Measures

Primary Outcomes (1)

• Progression-free survival (PFS)

  PFS is defined as the time from the date of initiation of zanzalintinib treatment to progression or death, whichever occurs first. The alive patients without progression are censored at the last follow-up.

  Through completion of follow-up (up to 6 years)

Secondary Outcomes (3)

• Objective response rate (ORR)

  Through completion of follow-up (up to 6 years)

• Overall survival (OS)

  Through completion of follow-up (up to 6 years)

• Number of participants with adverse events

  From start of treatment through 30 days after last dose of zanzalintinib (estimated to be 37 months)

Study Arms (1)

Zanzalintinib

EXPERIMENTAL

Zanzalintinib 60 mg taken by mouth once daily in 28-day cycles for up to 3 years.

Drug: Zanzalintinib

Interventions

Zanzalintinib DRUG

Provided by Exelixis

Zanzalintinib

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically confirmed high-grade poorly differentiated or well differentiated neuroendocrine tumor (with a Ki-67 of ≥20%), excluding small cell lung cancer (SCLC) and Merkel cell cancer. High-grade includes any neuroendocrine neoplasm with a Ki-67 of \>20% or with mitotic count of more than 20 mitoses per high power field or any poorly differentiated neoplasm or any neoplasm lacking these that is deemed high grade by pathology consensus, based on other markers (necrosis or IHC demonstrating p53 or RB mutation). This includes:
• High-grade well-differentiated neuroendocrine neoplasms
• Transformed NENs from a lower to a higher grade (patient may have some low grade and some high grade NENs)
• High-grade neoplasms with significant expression of neuroendocrine markers such as synaptophysin, chromogranin or INSM-1 or unknown origin neoplasms with gene expression signatures consistent with neuroendocrine lineage (as per validated tissue of origin testing, such as CancerType ID, after pathology consensus).
• Mixed neuroendocrine and non-neuroendocrine neoplasms (MiNEN), including MiNEN per WHO and mixed neoplasms not fulfilling criteria of MiNEN. The neuroendocrine component would need to be a high-grade neuroendocrine tumor as documented by pathology review.
• Note: For ambiguous cases, will consult with a designated expert pathologist.
• Measurable disease per RECIST 1.1.
• Current or prior somatostatin analogue therapy is allowed if clinically indicated.
• Patients must have received their initial course of chemotherapy and be eligible for a chemotherapy break with the most recent disease imaging assessment showing stable disease (SD) or a partial response (PR) by RECIST 1.1. The imaging showing stable disease or partial response should have occurred either during the chemotherapy or right after discontinuation of the chemotherapy treatment and before any other treatment. Reasons for treatment break can include physician or patient preference, completion of pre-specified treatment cycles, or toxicity. Patients intolerant of chemotherapy may also be eligible for the study, but they must have been treated with at least 2 cycles of chemotherapy and at least one imaging assessment on treatment or right after treatment showing PR or SD per RECIST 1.1. There is no limit for prior lines of non-chemotherapeutic regimens (including targeted agents, immunotherapy or radioligand treatment), but the most recent treatment prior to study initiation must contain chemotherapeutic agents.
• At least 18 years of age.
• ECOG performance status ≤ 2 (Karnofsky ≥ 80%).
• Adequate bone marrow and organ function as defined below:
• Absolute neutrophil count (ANC) ≥ 1.5 K/cumm without granulocyte colony-stimulating factor support within 2 weeks of screening laboratory sample collection.
• Platelets ≥ 100 K/cumm without transfusion within 2 weeks prior to screening laboratory sample collection.
• Hemoglobin ≥ 9.0 g/dL without transfusion within 2 weeks prior to screening laboratory sample collection.

You may not qualify if:

• Prior treatment with zanzalintinib (XL092) or cabozantinib (XL184).
• Another malignancy that requires active therapy and in the opinion of the Investigator would interfere with monitoring of radiologic assessments of response to Investigational Product, within 2 years before C1D1, except for superficial skin cancers, or localized, low-grade tumors deemed cured and not treated with systemic therapy. Incidentally diagnosed prostate cancer is allowed if assessed as stage ≤ T2N0M0 and Gleason score ≤ 6.
• Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 4 weeks before first dose of study treatment.
• Note: Eligible subjects must be neurologically asymptomatic and without corticosteroid treatment at the time of first dose of study treatment.
• Note: Base of skull lesions without definitive evidence of dural or brain parenchymal involvement are allowed.
• Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 2 weeks before C1D1.
• Receipt of any type of cytotoxic, biologic or other systemic anticancer therapy (including investigational) within 4 weeks before C1D1.
• Radiation therapy for bone metastasis within 2 weeks, any other radiation therapy within 4 weeks before first dose of study treatment. Systemic treatment with radionuclides within 6 weeks before first dose of study treatment. Subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible.
• Any complementary medications (eg, herbal supplements or traditional Chinese medicines) to treat the disease under study within 2 weeks before C1D1.
• Receipt of strong or moderate CYP3A4 inhibitors or inducers within 4 half-lives of C1D1. (This includes cimetidine, because of its potential to interfere with CYP3A4 mediated metabolism of zanzalintinib.)
• Use of concomitant medications that are known to prolong the QT interval within 4 half-lives of C1D1.
• Concomitant anticoagulation with oral anticoagulants (eg, warfarin, direct thrombin inhibitors) and platelet inhibitors (eg, clopidogrel). Allowed anticoagulants are the following:
• Prophylactic use of low-dose aspirin for cardioprotection (per local applicable guidelines) and low molecular weight heparins (LMWH).
• Therapeutic doses of LMWH or anticoagulation with direct factor Xa inhibitors rivaroxaban, edoxaban, or apixaban in subjects without known brain metastases who are on a stable dose of the anticoagulant for at least 1 week before C1D1 without clinically significant hemorrhagic complications from the anticoagulation regimen.
• Note: Subjects must have discontinued oral anticoagulants within 3 days or 5 half-lives prior to C1D1, whichever is longer.

Sponsors & Collaborators

• Washington University School of Medicine: lead
• Exelixis: collaborator

Study Sites (2)

Mayo Clinic - Rochester

Rochester, Minnesota, 55905, United States

NOT YET RECRUITING

Washington University School of Medicine

St Louis, Missouri, 63110, United States

RECRUITING

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Conditions

Neuroendocrine Tumors

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue

Study Officials

• Nikolaos Trikalinos, M.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Nikolaos Trikalinos, M.D.

CONTACT

314-273-4959; ntrikalinos@wustl.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 10, 2025
• First Posted: April 14, 2025
• Study Start: December 9, 2025
• Primary Completion (Estimated): December 31, 2034
• Study Completion (Estimated): December 31, 2034
• Last Updated: December 17, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)