Zanzalintinib for Bone Cancer

Overseen By John Livingston, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: VEGF-targeted TKIs, Anticoagulants

Disqualifiers: Soft tissue sarcoma, Cardiac disease, Hypertension, Hepatic impairment, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 16 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called zanzalintinib for individuals with advanced or metastatic bone cancer, specifically osteosarcoma, Ewing sarcoma, chondrosarcoma, and other bone sarcomas. The goal is to evaluate the effectiveness of this treatment on its own against these cancers. Individuals who have tried other treatments without success and have measurable cancer may be suitable for this study. Participants must have bone cancer that cannot be surgically removed and should not have previously received zanzalintinib. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Do I need to stop my current medications to join the trial?

The trial protocol does not clearly specify if you need to stop taking your current medications. However, you must not have received any anti-tumor therapy, including chemotherapy or investigational agents, within 21 days before starting the study treatment. Additionally, certain complementary medicines and specific anticoagulants must be stopped before the trial.

Is there any evidence suggesting that zanzalintinib is likely to be safe for humans?

Research has shown that zanzalintinib underwent testing in earlier human trials, indicating a positive safety profile since people have used it before. In these studies, participants generally tolerated zanzalintinib well, with no reports of serious or unexpected side effects.

Some trials combined zanzalintinib with other drugs like eribulin and atezolizumab, and these combinations also appeared safe. An independent committee closely monitored safety, providing additional confidence.

While any treatment can have side effects, the available data suggest that zanzalintinib has a strong safety record. It is likely safe for many people, though individual experiences may vary. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for bone cancer, which often include chemotherapy or radiation, Zanzalintinib targets the disease in a novel way. Researchers are excited about Zanzalintinib because it works by specifically interacting with the biological pathways that fuel cancer growth, potentially leading to more effective results with fewer side effects. This tailored approach could mean a more targeted attack on cancer cells, sparing more of the healthy cells compared to traditional therapies.

What evidence suggests that zanzalintinib might be an effective treatment for bone cancer?

Research has shown that zanzalintinib can slow or stop cancer growth by blocking proteins essential for tumor growth. In studies with patients who have advanced bone cancers, zanzalintinib extended survival without cancer progression. For those whose cancer has returned or who lack other treatment options, this drug offers new hope. Early findings suggest that zanzalintinib could be effective for people with advanced bone cancers. While more information is needed, the initial results are promising. ^{1 2 3 4 6}

Who Is on the Research Team?

John Livingston, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

Adults (≥18 years) with advanced or metastatic bone sarcoma who have measurable disease, can consent to sample collection for studies, and agree to use contraception. They should not have had more than two prior systemic therapies in the advanced setting, must weigh at least 40 kg, and have an ECOG performance status of 0-2. Exclusions include recent investigational drug use, known allergies to study drugs, detectable HIV/HBV/HCV viral load, certain heart conditions or psychiatric illnesses that affect compliance.

Inclusion Criteria

Patients must have measurable disease per RECIST v1.1

INR ≤ 1.5 and activated partial thromboplastin time (aPTT) < 1.2 x upper limit of normal (ULN), except subjects on anticoagulation

All patients must agree to consent and co-enroll on MD Anderson MOSAIC protocol for sample collection and correlative studies

Exclusion Criteria

Prior receipt of an investigational study drug and/or procedure within 21 days of study day 1

Patients with known sensitivity to the study agents and/or previously identified allergy or hypersensitivity to components of treatment

Patients with known human immunodeficiency virus (HIV) infection with detectable viral load

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive zanzalintinib monotherapy for advanced/metastatic bone sarcomas

16 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Long-term follow-up

Monitoring of safety and adverse events through study completion

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Zanzalintinib

Trial Overview The trial is testing Zanzalintinib as a single-agent therapy for patients with advanced/metastatic bone sarcomas. It aims to evaluate the effectiveness of this treatment in those who've relapsed after conventional therapy or where no standard care exists.

How Is the Trial Designed?

Group I: Phase 2 Cohorts A, B, C, D: Treatment with Zanzalintinib Experimental Treatment 1 Intervention

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

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Exelixis

Industry Sponsor

Trials

126

Recruited

20,500+

Michael M. Morrissey

Exelixis

Chief Executive Officer since 2010

PhD in Chemistry from Harvard University, BSc in Chemistry from the University of Wisconsin

Vicki L. Goodman

Exelixis

Chief Medical Officer since 2022

MD

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT07193550

A Phase 2 Trial of Zanzalintinib in Advanced/Metastatic ... To estimate the progression-free survival (PFS) and overall survival in patients with locally advanced or metastatic bone sarcomas receiving zanzalintinib. To ...

2. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2024-06742

XL092 (Zanzalintinib) for the Treatment of Patients with ... Current standard treatment for leiomyosarcoma only shows a progression-free survival of 4-6 months.

3. withpower.com withpower.com/trial/phase-2-bone-neoplasms-4-2026-4f66e

Zanzalintinib for Bone Cancer · Info for Participants It aims to evaluate the effectiveness of this treatment in those who've relapsed after conventional therapy or where no standard care exists. How Is the Trial ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11485978/

STELLAR-303: randomized phase III study of zanzalintinib ... Zanzalintinib is a novel oral investigational drug that can slow or stop cancer growth. It works by blocking certain proteins that play important roles in the ...

5. centerwatch.com centerwatch.com/clinical-trials/listings/NCT06957431/zanzalintinib-combined-with-eribulin-in-advanced-liposarcoma-and-leiomyosarcoma

Zanzalintinib Combined With Eribulin in Advanced ... The investigators hypothesize that the combination of eribulin and zanzalintinib will be tolerable and lead to improved progression-free ...

6. onclive.com onclive.com/view/zanzalintinib-plus-atezolizumab-boosts-os-in-previously-treated-non-msi-h-mcrc

Zanzalintinib Plus Atezolizumab Boosts OS in Previously ... Zanzalintinib plus atezolizumab improved overall survival in previously treated, non–MSI-H metastatic colorectal cancer.