Zanzalintinib for Leiomyosarcoma

Overseen By Study Coordinator

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Northwestern University

Must not be taking: Anticoagulants, Platelet inhibitors, Herbal supplements

Disqualifiers: Brain metastases, Uncontrolled hypertension, Active infection, 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: 31

Duration: Up to 6 months

29 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether the drug zanzalintinib (XL092) can effectively treat leiomyosarcoma, a type of cancer that has spread or cannot be removed by surgery. The goal is to determine if XL092, which inhibits cancer cell growth, can extend the time before the disease worsens compared to current treatments. Ideal participants have leiomyosarcoma that has spread or cannot be surgically removed and have tried at least two other treatments. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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

The trial does not specify if you need to stop all current medications, but you cannot take certain medications like small-molecule kinase inhibitors within 14 days before starting the trial. You also need to stop taking oral anticoagulants at least 3 days before the trial. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that zanzalintinib (XL092) is likely to be safe for humans?

Research has shown that zanzalintinib, also known as XL092, has been tested in earlier studies to assess its safety and tolerability. One study combined it with nivolumab and yielded promising results, with 63% of patients responding positively and 90% achieving disease control. This indicates that the treatment effectively managed the disease in many patients.

Regarding safety, previous studies found zanzalintinib to be generally well-tolerated, with most participants not experiencing severe side effects. However, some unwanted effects were reported, though specific details are not well-documented in the sources.

Zanzalintinib is currently in a phase 2 trial for leiomyosarcoma, suggesting some confidence in its safety from earlier testing. However, it is still under study to ensure its safety and efficacy for this specific condition.

Participation in such a clinical trial involves close monitoring for any side effects, allowing for quick response to any issues that arise. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for leiomyosarcoma, which often include traditional chemotherapy and radiation therapies, Zanzalintinib (XL092) offers a novel approach. It targets specific pathways involved in tumor growth, potentially leading to more effective results with fewer side effects. Researchers are excited about Zanzalintinib because it may provide a new avenue for managing leiomyosarcoma, especially for patients who haven't responded well to conventional therapies. By focusing on targeted treatment, Zanzalintinib could offer hope for improved outcomes in this challenging condition.

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

Studies have shown that the current treatment for leiomyosarcoma helps patients live without cancer progression for only 4-6 months. Zanzalintinib (XL092), the investigational treatment in this trial, blocks signals that aid cancer cell growth and spread. Earlier research has shown that this drug might slow or halt tumor growth. In previous studies with a similar type of cancer, zanzalintinib combined with another medicine had a high response rate, with many patients experiencing tumor shrinkage or halted growth. This suggests zanzalintinib could be a promising option for patients with advanced or difficult-to-remove leiomyosarcoma. ^{1 2 4 6 7}

Who Is on the Research Team?

Pedro Hermida de Viveiros, MD

Principal Investigator

Northwestern University

Are You a Good Fit for This Trial?

This trial is for patients with leiomyosarcoma, a type of sarcoma that has spread or can't be removed by surgery. Participants must meet certain health conditions to join, but specific inclusion and exclusion criteria are not provided in the given information.

Inclusion Criteria

Patients must have measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1

Leukocytes (white blood cells [WBC]) ≥ 3,000/mcL

I've had more than 2 cancer treatments, but no more than 2 were tyrosine kinase inhibitors.

Exclusion Criteria

I haven't taken any kinase inhibitor medication in the last 14 days.

I have had more than two prior treatments with tyrosine kinase inhibitors.

I am receiving ongoing treatment for side effects from previous radiation therapy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive XL092 orally once daily on days 1-14 of each cycle, with cycles repeating every 14 days

Up to 6 months

Bi-weekly visits for treatment and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

Up to 5 years

Follow-up at 30 days, then every 12 weeks for 2 years, followed by every 6 months

What Are the Treatments Tested in This Trial?

Interventions

• Zanzalintinib (XL092)

Trial Overview

The trial is testing XL092 (Zanzalintinib), which may interfere with tumor growth in metastatic or unresectable leiomyosarcoma. It's a phase II study to see if this drug can improve survival compared to current treatments.

How Is the Trial Designed?

Group I: Treatment (XL092) Experimental Treatment 5 Interventions

Patients receive XL092 PO QD on days 1-14 of each cycle. Cycles repeat every 14 days in the absence of disease progression or unacceptable toxicity. Patients also undergo ECHO or MUGA at screening and then as clinically indicated, and blood sample collection on study and CT throughout the study.

Who Is Running the Clinical Trial?

Northwestern University

Lead Sponsor

Trials

1,674

Recruited

989,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

A case report highlights the treatment of a woman in her late 50s with metastatic leiomyosarcoma (LMS) that had a high tumor mutational burden (TMB) using pembrolizumab, an immunotherapy drug.

This case suggests that patients with LMS and high TMB may respond differently to immunotherapy, which has generally been ineffective for most sarcoma patients, indicating a potential new avenue for treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PD-1 Inhibition in metastatic high tumour mutational burden (TMB) leiomyosarcoma with clinicopathological correlates. Pandita, D., Dave, M., Schulte, B.[2023]

In a Phase II study involving 21 patients with recurrent uterine leiomyosarcoma, alisertib showed no objective tumor responses, indicating it may not be an effective treatment for this condition.

The study found that while 38.1% of patients had stable disease, the event-free survival rate at 6 months was 0%, suggesting that alisertib does not provide meaningful clinical benefit as a single agent in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 2 study of alisertib (MLN8237) in recurrent or persistent uterine leiomyosarcoma: An NRG Oncology/Gynecologic Oncology Group study 0231D. Hyman, DM., Sill, MW., Lankes, HA., et al.[2021]

The ATR kinase inhibitor BAY1895344 showed significant effectiveness in inhibiting tumor growth and prolonging survival in patient-derived xenograft models of uterine leiomyosarcoma (uLMS) with ATRX mutations, with median survival increasing from 12.5 to 42 days for one model and from 33 to 60 days for another.

Treatment with BAY1895344 did not result in significant toxicity, indicating a favorable safety profile, which supports the need for clinical trials in uLMS patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Elimusertib (BAY1895344), a novel ATR inhibitor, demonstrates in vivo activity in ATRX mutated models of uterine leiomyosarcoma. Harold, J., Bellone, S., Manavella, DD., et al.[2023]

Research on treating leiomyosarcoma (LMS) is limited, highlighting a need for more effective therapies.

This report presents a case where a patient with recurrent LMS experienced disease regression after treatment with pembrolizumab and lenvatinib, suggesting potential efficacy for this combination therapy in LMS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A case of pembrolizumab and lenvatinib as an alterntive therapy for leiomyosarcoma. Mehta, N., Lee, SS., Salame, G.[2023]

Leiomyosarcoma, a common type of soft tissue sarcoma, accounts for about 20% of sarcomas and is associated with a high rate of metastasis, highlighting the urgent need for effective systemic therapies.

Current conventional treatments for advanced or metastatic leiomyosarcoma show poor efficacy and prognosis, indicating a significant gap in effective treatment options and the necessity for well-designed clinical studies to improve patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

What Clinical Trials Are Needed for Treatment of Leiomyosarcoma? Kasper, B., D'Ambrosio, L., Davis, EJ., et al.[2022]

Citations

1.

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. XL092, a tyrosine kinase inhibitor, interferes with cell ...

2.

trialx.com

trialx.com/clinical-trials/listings/300292/xl092-zanzalintinib-for-the-treatment-of-patients-with-metastatic-or-unresectable-leiomyosarcoma/?&radius=50

XL092 (Zanzalintinib) for the Treatment of Patients With ...

Current standard treatment for leiomyosarcoma only shows a progression-free survival of 4-6 months. XL092, a tyrosine kinase inhibitor, ...

3.

ir.exelixis.com

ir.exelixis.com/news-releases/news-release-details/exelixis-announces-encouraging-results-phase-1b2-stellar-002

Press Release - Exelixis, Inc.

Zanzalintinib in combination with nivolumab demonstrated an objective response rate of 63% and a disease control rate of 90%.

4.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11916370/

STELLAR-304: a phase III study of zanzalintinib (XL092) plus ...

Cabozantinib showed significant benefits in PFS (9.0 vs 5.6 months, respectively; HR for cabozantinib vs sunitinib: 0.60, 95% CI: 0.37–0.97; p = 0.019) and ...

5.

withpower.com

withpower.com/trial/zanzalintinib-for-leiomyosarcoma-5495c

Zanzalintinib for Leiomyosarcoma

Current standard treatment for leiomyosarcoma only shows a progression-free survival of 4-6 months. XL092, a tyrosine kinase inhibitor, interferes with cell ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12509647/

EXACT: a randomized phase II trial of XL092 (zanzalintinib ...

The primary endpoint is overall response rate at 6 months as per investigator assessed RECIST 1.1. Secondary endpoints include progression- free ...

7.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05176483

NCT05176483 | Study of XL092 in Combination With ...

This is a multicenter Phase 1b, open label, dose-escalation and cohort-expansion study, evaluating the safety, tolerability, PK, preliminary antitumor ...