Zanzalintinib + Pembrolizumab for Soft Tissue Sarcoma

Overseen By Michael S Nakazawa, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Anticoagulants, CYP3A4 inhibitors

Disqualifiers: Cardiac disease, Hypertension, Autoimmune, 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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if combining zanzalintinib and pembrolizumab can manage certain types of advanced soft tissue sarcoma, which affects tissues like muscles and fat. Participants will receive both medications to evaluate their combined effectiveness against the cancer. This trial may suit adults with undifferentiated pleomorphic sarcoma, myxofibrosarcoma, high-grade pleomorphic sarcoma, or undifferentiated sarcoma. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

Is there any evidence suggesting that zanzalintinib and pembrolizumab are likely to be safe for humans?

Research has shown that pembrolizumab was tested for safety in patients with advanced soft-tissue sarcoma. Most patients tolerated the treatment well, although some experienced manageable side effects.

Specific safety information for the combination of zanzalintinib and pembrolizumab is not yet available. However, the trial's Phase 2 status indicates that earlier studies deemed these drugs safe enough for a larger group. This suggests a positive safety profile, but monitoring for new information from ongoing trials remains important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Zanzalintinib combined with Pembrolizumab for soft tissue sarcoma because this treatment approach targets cancer cells in a unique way. Most current treatments for soft tissue sarcoma rely on surgery, radiation, and chemotherapy. However, the combination of Zanzalintinib and Pembrolizumab leverages a new mechanism by enhancing the immune system's ability to identify and attack cancer cells. Zanzalintinib is believed to work by inhibiting certain pathways that tumors use to grow, while Pembrolizumab is an immunotherapy that unleashes the immune system to fight the cancer. This dual approach could potentially lead to more effective and targeted treatments, offering new hope for patients.

What evidence suggests that zanzalintinib and pembrolizumab might be effective for soft tissue sarcoma?

Research has shown that using zanzalintinib with pembrolizumab may help treat soft tissue sarcoma, a type of cancer. In a recent study, 71.4% of patients with this cancer type experienced a significant reduction in active cancer cells in their tumors. Pembrolizumab alone has also improved outcomes, with 67% of patients remaining disease-free after two years, compared to 52% of those who did not receive it. This trial will evaluate the combination of these two treatments, which might offer better results for patients with advanced or spreading soft tissue sarcoma. ^{1 6 7 8 9}

Who Is on the Research Team?

Michael S Nakazawa, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for individuals with certain advanced or metastatic soft-tissue sarcomas (UPS, MFS, HGPS, HGUS). Participants must meet specific criteria that the study defines. The full list of inclusion and exclusion criteria is not provided here.

Inclusion Criteria

Consent to MD Anderson companion laboratory protocol 2014-0938 for correlative analyses of biopsies obtained in this trial.

Participants must have measurable disease as defined by specific criteria.

I have a history or symptoms of heart disease and need a risk assessment.

Exclusion Criteria

Participants with psychiatric illness/social situations that would limit compliance with study requirements.

I have a condition that prevents my body from absorbing nutrients properly.

Known positive test for tuberculosis infection.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive zanzalintinib and pembrolizumab to control select subtypes of advanced/metastatic soft-tissue sarcoma

6 months

Regular visits as per protocol

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab
• Zanzalintinib

Trial Overview

The trial is testing the effectiveness of zanzalintinib combined with pembrolizumab in controlling select subtypes of soft-tissue sarcoma. It's a Phase 2 study which means it focuses on how well these drugs work and their safety.

How Is the Trial Designed?

Group I: Single Arm Experimental Treatment 2 Interventions

Treatment with Zanzalintinib + Pembrolizumab

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

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clinicaltrials.gov

clinicaltrials.gov/study/NCT07283731

Phase 2 Trial of Zanzalintinib and Pembrolizumab in Select ...

Because no dosing or adverse event data are currently available on the use of zanzalintinib in combination with pembrolizumab in participants < ...

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11985850/

The outcomes and treatment strategies in metastatic soft ...

Historical data showed that the rate of 5-year OS was about 22% in 1989, which increased to about 61% in 2018 in the metastatic setting (18).

3.

firstwordpharma.com

firstwordpharma.com/story/5912635

Positive Data from Phase II Trial in Soft Tissue Sarcoma ...

To see 71.4% of soft tissue sarcoma patients achieving a pathologic response defined as ≥35% of hyalinization/fibrosis combined with low viable ...

4.

dgalerts.docguide.com

dgalerts.docguide.com/ncov-home/article/pembrolizumab-improves-outcomes-for-patients-with-soft-tissue-sarcoma?article_title=Pembrolizumab%20Improves%20Outcomes%20for%20Patients%20With%20Soft%20Tissue%20Sarcoma&article_id=5912097

Pembrolizumab Improves Outcomes for Patients With Soft ...

In a total of 127 patients, the 2-year disease-free survival rate was 52% for the control group and 67% for the experimental group, indicating ...

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mdpi.com

mdpi.com/2072-6694/17/10/1724

From Intensification to Optimization: Balancing Efficacy ...

Patients with Grade 2 tumors (n = 13) in the RWD cohort showed favorable survival outcomes, achieving a 2-year OS of 100% and DFS of 75%. In contrast, patients ...

6.

clin.larvol.com

clin.larvol.com/trial-detail/NCT07283731

Phase 2 Trial of Zanzalintinib and Pembrolizumab in Select ...

Outcome Measure, Measure Description, Time Frame ; Safety and adverse events (AEs), Incidence of Adverse Events, Graded According to National Cancer Institute ...

7.

trial.medpath.com

trial.medpath.com/clinical-trial/7e857172ad81f3e8/nct07283731-zanzalintinib-pembrolizumab-advanced-metastatic-sarcoma

Phase 2 Trial of Zanzalintinib and Pembrolizumab in Select ...

Phase 2 Trial of Zanzalintinib and Pembrolizumab in Select Subtypes of Advanced/Metastatic Soft-tissue Sarcoma ... Outcome data and publication updates.

8.

clinicaltrials.gov

clinicaltrials.gov/study/NCT06968988

Study Details | NCT06968988 | Zanzalintinib in ...

The investigators hypothesize that zanzalintinib in combination with ipilimumab and nivolumab will be well tolerated and serve as a potential therapeutic ...

9.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/28988646/

Pembrolizumab in advanced soft-tissue sarcoma and bone ...

We assessed pembrolizumab, an anti-PD-1 antibody, for safety and activity in patients with advanced soft-tissue sarcoma or bone sarcoma.