Actively Recruiting
Phase 2 Trial of Zanzalintinib and Pembrolizumab in Select Subtypes of Advanced/Metastatic Soft-Tissue Sarcoma
Led by M.D. Anderson Cancer Center · Updated on 2026-04-17
20
Participants Needed
1
Research Sites
104 weeks
Total Duration
On this page
Sponsors
M
M.D. Anderson Cancer Center
Lead Sponsor
E
Exelixis
Collaborating Sponsor
AI-Summary
What this Trial Is About
Researchers are evaluating whether the combination of zanzalintinib and pembrolizumab can help control select subtypes of advanced or metastatic soft-tissue sarcoma, including undifferentiated pleomorphic sarcoma (UPS), myxofibrosarcoma (MFS), high-grade pleomorphic sarcoma (HGPS), and high-grade undifferentiated sarcoma (HGUS). This phase 2 trial aims to measure how long participants remain free from disease progression or death, assess response rates, and monitor any serious side effects from the treatment. Participants will receive a combination treatment of zanzalintinib taken orally and pembrolizumab administered intravenously. The study involves a single experimental group where participants receive both drugs. Treatment schedules, dosing details, and the duration of therapy will follow the study protocol to assess effects and safety. There is no placebo or comparison group in this trial. During the study, participants will undergo regular evaluations to monitor their disease status and side effects. Assessments include imaging scans to measure tumor response, safety monitoring for adverse events, and laboratory tests to check organ function. Researchers will track progression-free survival and observe any severe toxicities through the study completion, which will average about one year. Participants will be followed closely to understand how the treatment affects their cancer and overall health.
CONDITIONS
Brief Title
Phase 2 Trial of Zanzalintinib and Pembrolizumab in Select Subtypes of Advanced/Metastatic Soft-tissue Sarcoma
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Participants must have confirmed diagnosis of undifferentiated pleomorphic sarcoma, myxofibrosarcoma, high grade pleomorphic sarcoma, or high grade undifferentiated sarcoma.
- Participants must be 18 years of age or older.
- ECOG performance status must be 2 or less (Karnofsky 60% or higher).
- Participants must have measurable disease with at least one lesion of specified size measurable by imaging or clinical exam.
- At least 4 weeks must have passed since prior chemotherapy.
- At least 2 weeks since radiation therapy for bone metastases, and at least 4 weeks since other radiation therapy before starting study treatment.
- At least 6 weeks since systemic radionuclide treatment before starting study treatment.
- Adequate organ and marrow function as defined by specified laboratory values within 14 days before first dose.
- Participants with chronic hepatitis B must have undetectable viral load on therapy; those with hepatitis C must be treated and cured or have undetectable viral load if on treatment.
- Participants with treated brain metastases must show no progression for at least 4 weeks and meet corticosteroid use criteria.
- Participants with new or progressive brain metastases may be eligible if immediate CNS treatment is not required.
- Participants with certain prior or concurrent malignancies may be eligible if not interfering with study assessments.
- Cardiac function must be NYHA class 2B or better.
- Women of childbearing potential and men must agree to use effective contraception during and after the study as specified.
- Females must not be pregnant.
- Participants must be able to understand and comply with study requirements and provide informed consent.
- Consent to companion laboratory protocol for biopsy analyses.
You will not qualify if you...
- Prior treatment with immune checkpoint inhibitors or zanzalintinib.
- Use of any small molecule kinase inhibitor within 2 weeks before first dose.
- Unresolved adverse events from prior cancer therapy greater than Grade 1, except alopecia.
- Ongoing complications from prior radiation therapy or recent radiation or systemic radionuclide therapy within specified time frames.
- Use of other investigational agents or anticancer therapies within 4 weeks before starting study treatment.
- Use of oral anticoagulants or platelet inhibitors except specified low-dose or stable anticoagulation regimens.
- Use of complementary medications to treat the disease within 2 weeks before first dose.
- Uncontrolled or significant illnesses including unstable cardiovascular conditions, uncontrolled hypertension, recent stroke, or thrombotic events.
- Prior myocarditis.
- Gastrointestinal disorders with high risk of perforation or obstruction within 6 months unless resolved.
- Significant bleeding history or clinically relevant hematuria, hematemesis, or hemoptysis within 12 weeks.
- Active infections needing systemic treatment.
- Serious non-healing wounds or ulcers except tumor-associated skin lesions.
- Malabsorption syndrome or uncompensated hypothyroidism.
- Moderate to severe liver impairment or need for dialysis.
- History of organ or stem cell transplant.
- Allergic reactions to similar study drugs.
- Use of moderate or strong CYP3A4 inhibitors.
- Certain HIV conditions with unstable viral load or low CD4 count.
- Psychiatric or social conditions limiting compliance.
- Pregnancy or breastfeeding.
- Recent major or minor surgery without complete healing.
- QTcF interval over 480 ms by ECG.
- Inability to swallow tablets or suspensions.
- Other malignancies requiring active therapy interfering with study assessments.
- Suspected or recent autoimmune disease.
- Positive tuberculosis test with disease evidence.
- History or signs of pneumonitis or lung disease.
- Abnormal thyroid hormone levels without approval.
- Immunodeficiency or recent systemic steroid or immunosuppressive therapy.
- Recent live vaccine administration.
- Other conditions compromising safety or study completion.
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Duration - Until disease progression or unacceptable toxicity
Participants receive treatment with Zanzalintinib taken orally and Pembrolizumab given intravenously to manage their advanced or metastatic soft-tissue sarcoma.
Regular visits for treatment administration and safety monitoring
Duration - Up to 1 year after treatment completion
Participants are monitored for safety and adverse events after completing treatment, including assessments for progression-free survival and overall response.
Periodic visits for safety assessments and outcome evaluations
Trial Site Locations
Total: 1 location
1
MD Anderson Cancer Center
Houston, Texas, United States, 77030
Actively Recruiting
Research Team
M
Michael S Nakazawa, MD
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NA
Model
SINGLE_GROUP
Primary Purpose
TREATMENT
Number of Arms
1
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