Zanzalintinib in Unresectable and Progressive MPGGs

NCT07714551 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 26-340
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 2

Brief Summary

This study is to examine the effects of oral daily zanzalintinib in participants with unresectable, progressive metastatic pheochromocytoma or paraganglioma.

Conditions

Pheochromocytoma; Paraganglioma

Keywords

Pheochromocytoma; Paraganglioma; Metastatic pheochromocytoma or paraganglioma; Unresectable, progressive advanced pheochromocytoma/paraganglioma

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  ORR was defined as the percentage of participants achieving complete response (CR) or partial response (PR) on treatment based on RECIST 1.1 criteria. Per RECIST 1.1 for target lesions: CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions.

  Assessed every 8 weeks during treatment. The estimated treatment duration is up to 16 months.

Secondary Outcomes (7)

• Median Progression-Free Survival (PFS)

  Assessed every 8 weeks during treatment. The treatment duration is up to 16 months. If treatment discontinued prior to progression, participants will be followed every 3 months for up to 52 weeks or until death.

• Median Overall Survival (OS)

  Treatment duration is up to 16 months. Following treatment discontinuation, participants will be followed every 3 months for up to 52 weeks or until death.

• Global Adverse Event (AE) Rate

  AE will be assessed every 2 weeks through Week 8 and every 4 weeks thereafter until the end of treatment (up to 16 months).

• Blood Pressure Control Rate

  Assessed every 8 weeks on treatment. Treatment duration is up to 16 months.

• Biochemical Response Rate

  Treatment duration is up to 16 months.

Study Arms (1)

Zanzalintinib

EXPERIMENTAL

Participants receive zanzalintinib orally once daily.

Drug: Zanzalintinib

Interventions

Zanzalintinib DRUG

Route: Oral Schedule: Daily

Also known as: XL092

Zanzalintinib

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years. As no dosing or adverse event data are currently available in participants \< 18 years of age, children and adolescents are excluded from this study.
• Documentation of Disease
• Histologic Documentation: Histologically-proven advanced (metastatic or unresectable primary) pheochromocytoma or paraganglioma.
• Stage: Advanced (metastatic or unresectable primary) disease
• Tumor Site: Histologically-proven pheochromocytoma or paraganglioma
• Radiographic Evaluation: Radiographic evidence of disease progression by RECIST v1.1 criteria in the 12 months prior to registration.
• Measurable disease
• Lesions must be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 1 cm with CT or MRI (or ≥ 1.5 cm for lymph nodes). Non-measurable disease includes disease smaller than these dimensions or lesions considered truly non-measurable including: leptomeningeal disease, ascites, pleural or pericardial effusion, lymphangitic involvement of skin or lung.
• Prior Treatment
• Prior treatment with other somatostatin analog, chemotherapy, radiotherapy (including peptide radionuclide receptor therapy \[PRRT\]), or surgery is permitted.
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.
• Organ and marrow function and laboratory values as follows within 4 days prior to the first dose of zanzalintinib:
• Absolute neutrophil count (ANC) ≥ 1500/mm3without colony stimulating factor support
• Platelets ≥ 100,000/mm3
• Hemoglobin ≥ 9 g/dL

You may not qualify if:

• Received cytotoxic chemotherapy (including investigational cytotoxic chemotherapy) or biologic agents (eg, cytokines or antibodies) within 3 weeks, or nitrosoureas/ mitomycin C within 6 weeks before the first dose of study treatment.
• Prior treatment with zanzalintinib
• Radiation therapy for bone metastasis within 2 weeks, any other external radiation therapy within 4 weeks before the first dose of study treatment. Subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible.
• Received radionuclide treatment (i.e. I 131 meta-iodo- benzyl guanidine) within 6 months of the first dose of study treatment
• Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 14 days before the first dose of study treatment.
• Receipt of any other type of investigational agent within 28 days before the first dose of study treatment.
• The subject has not recovered to baseline or CTCAE ≤ Grade 1 from toxicity due to all prior therapies except alopecia, fatigue, and other non-clinically significant AEs.
• Prothrombin time (PT)/ International Normalized Ratio (INR) or partial thromboplastin time (PTT) test ≥ 1.3 the laboratory ULN within 7 days before the first dose of study treatment.
• The subject requires concomitant treatment, in therapeutic doses, with anticoagulants such as warfarin or warfarin-related agents, heparin, thrombin, or antiplatelet agents (eg, clopidogrel). Low dose aspirin (≤ 81 mg/day), , prophylactic low molecular weight heparin (LMWH), and or specified direct Fxa inhibitors rivaroxaban, edoxaban, or apixabanare permitted in subjects without known brain metastases.
• Subjects must have discontinued oral anticoagulants within 3 days or 5 half-lives prior to first dose of study treatment, whichever is longer.
• The subject requires chronic concomitant treatment of strong CYP3A4 inducers (eg, dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentin, phenobarbital, and St. John's Wort).
• Any complementary medications (eg, herbal supplements or traditional Chinese medicines) to treat the disease under study within 2 weeks before first dose of study treatment.
• 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 enrollment. Note: Base of skull lesions without definitive evidence of dural or brain parenchymal involvement are allowed.
• The subject has experienced any of the following: clinically significant gastrointestinal bleeding within 6 months before the first dose of study treatment hemoptysis of ≥ 0.5 teaspoon (2.5ml) of red blood within 3 months before the first dose of study treatment
• ·any other signs indicative of pulmonary hemorrhage within 3 months before the first dose of study treatment

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Exelixis: collaborator

Study Sites (2)

Brigham and Women's Hospital (BWH)

Boston, Massachusetts, 02215, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Conditions

Pheochromocytoma; Paraganglioma

Condition Hierarchy (Ancestors)

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

Study Officials

• Kimbery Perez, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kimberly Perez, MD

CONTACT

6176326491; Kimberly_Perez@DFCI.HARVARD.EDU

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 15, 2026
• First Posted: July 20, 2026
• Study Start (Estimated): January 9, 2027
• Primary Completion (Estimated): January 1, 2031
• Study Completion (Estimated): January 1, 2032
• Last Updated: July 20, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Belfer office for Dana -Farber Innovations (BODFI) at innovations@dfci.harvard.edu

Locations

US (2)