A Phase 2 Trial of Zanzalintinib in Advanced/Metastatic Bone Sarcomas (ZAMBONE)

NCT07193550 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 2025-0912
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

Brief Summary

To study the treatment efficacy of zanzalintinib monotherapy in patients with advanced and/or metastatic bone sarcomas.

Conditions

Bone Sarcomas

Outcome Measures

Primary Outcomes (1)

• Safety and Adverse Events (AEs)

  Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0

  Through study completion; an average of 1 year

Study Arms (1)

Phase 2 Cohorts A, B, C, D: Treatment with Zanzalintinib

EXPERIMENTAL

Four cohorts of patients based on biology of the disease will be included in this trial:

Drug: Zanzalintinib

Interventions

Zanzalintinib DRUG

Participants will take zanzalintinib 100mg daily by mouth

Also known as: XL092

Phase 2 Cohorts A, B, C, D: Treatment with Zanzalintinib

Eligibility Criteria

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

You may qualify if:

• Patients ≥ 18 years old with pathologically confirmed unresectable locally advanced or metastatic bone sarcoma in one of the following categories: Cohort A - Osteosarcoma, Cohort B - Ewing sarcoma, Cohort C - Chondrosarcoma (conventional, grades 2-3), Cohort D - Other primary sarcoma of bone including but not limited to dedifferentiated chondrosarcoma, undifferentiated pleomorphic sarcoma (UPS) of bone, chordoma, and non-Ewing's round cell sarcomas of bone.
• chondrosarcoma, undifferentiated pleomorphic sarcoma (UPS) of bone, chordoma, and non-Ewing's round cell sarcomas of bone.
• Patients with conventional chondrosarcoma (Cohort C) must demonstrate evidence of disease progression by RECIST 1.1 within 12 weeks of trial enrollment
• Patients must have relapsed or become refractory to conventional therapy, receiving at least 1 prior line of systemic therapy unless no standard of care exists.
• Patients may have received no more than 2 prior lines of systemic therapy in the advanced/metastatic setting.
• Multi-agent and/or alternating neoadjuvant/adjuvant standard of care chemotherapy will be counted as 1 line of systemic therapy if given for metastatic disease. Otherwise, neoadjuvant/adjuvant chemotherapy for localized disease does not apply towards the limitation regarding prior lines of systemic therapy.
• Patients must have a performance status corresponding to ECOG scores of 0, 1 or 2 (Karnofsky ≥60%).
• Weight \>/= 40 kg.
• Patients must have measurable disease per RECIST v1.1
• Prior radiation will be allowed assuming there is measurable disease based upon RECIST 1.1 and at least 21 days from the completion of all radiation prior to initiation of study treatment. (Note: Previously irradiated lesions can be considered as measurable disease only if progressive disease has been unequivocally documented at that site since radiation)
• Hematological function, as follows:
• Absolute neutrophil count (ANC) ≥ 1500/mm3 (growth factor/G-CSF permitted)
• Platelet count ≥ 100,000/mm3
• Hemoglobin \> 9 g/dL.
• INR ≤ 1.5 and activated partial thromboplastin time (aPTT) \< 1.2 x upper limit of normal (ULN), except subjects on anticoagulation.

You may not qualify if:

• Prior treatment with zanzalintinib.
• Patients with primary soft tissue sarcoma with metastasis to bone.
• o Patients with histologically confirmed Ewing's sarcoma with either bone or soft tissue primary site are eligible for enrollment in Cohort B
• Patients with known sensitivity to the study agents and/or previously identified allergy or hypersensitivity to components of treatment
• Patients previously treated with other VEGF-targeted TKIs (including but not limited to cabozantinib, regorafenib, pazopanib, or similar).
• Receipt of any small molecule kinase inhibitor (including investigational within 2 weeks before first dose of study treatment.
• Untreated central nervous system metastatic disease, leptomeningeal disease, or cord compression.
• Active infection requiring intravenous (IV) antibiotics within 2 weeks of study enrollment.
• Prior receipt of an investigational study drug and/or procedure within 21 days of study day 1.
• Anti-tumor therapy within 21 days of study day 1 including chemotherapy, antibody therapy, or other investigational agent.
• Radiation therapy for bone metastasis within 2 weeks, any other radiation therapy within 4 weeks, or systemic treatment with radionuclides within 6 weeks before first dose of study treatment; ongoing clinically relevant complications from prior radiation therapy are not eligible.
• Any complementary medicine such as herbal supplements, Chinese medicines, or other non-prescription medications being used for the treatment of bone sarcoma within 2 weeks prior to first dose of treatment as detailed in section5.5.
• History of cardiac disease: congestive heart failure New York Heart Association (NYHA) class \> II, unstable angina (angina symptoms at rest), new-onset angina (within the past 6 months before study entry), myocardial infarction within the past 6 months before study entry.
• Uncontrolled hypertension defined as sustained blood pressure (BP) \> 140 mm Hg systolic or \> 90 mm Hg diastolic despite optimal antihypertensive treatment
• Moderate or severe hepatic impairment, i.e. Child-Pugh class B or C.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Exelixis: collaborator

Study Sites (1)

The University of Texas M. D. Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Related Links

• MD Anderson Cancer Center Website

MeSH Terms

Conditions

Bone Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Bone Diseases; Musculoskeletal Diseases

Study Officials

• John Livingston, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

John Livingston, MD

CONTACT

(713) 792-3626; jalivingston@mdanderson.org

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: September 24, 2025
• First Posted: September 26, 2025
• Study Start: December 5, 2025
• Primary Completion (Estimated): October 31, 2029
• Study Completion (Estimated): October 31, 2031
• Last Updated: February 27, 2026

Record last verified: 2026-02

Locations

US (1)