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Phase 2Phase 2NCT07283731

Phase 2 Trial of Zanzalintinib and Pembrolizumab in Select Subtypes of Advanced/Metastatic Soft-tissue Sarcoma

A Phase 2 study testing Zanzalintinib and Pembrolizumab in people with Phase 2 and Zanzalintinib, run by M.D. Anderson Cancer Center at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

To learn if zanzalintinib and pembrolizumab can help to control select subtypes of advanced/metastatic soft-tissue sarcoma (UPS, MFS, HGPS, and HGUS Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Phase 2, Zanzalintinib, Pembrolizumab
What is being tested?
Zanzalintinib and Pembrolizumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
20 participants
Where
1 siteUnited States
Study dates
14 Apr 2026to 1 Nov 2030
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

None listed.

Who cannot join

  • Prior treatment with immune checkpoint inhibitors (ICIs)
  • Prior treatment with zanzalintinib
  • Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 2 weeks before first dose of study treatment.
  • Participants who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities > Grade 1) with the exception of alopecia.
  • Participants with clinically relevant ongoing complications from prior radiation therapy are not eligible. Additionally, if participants have received radiation therapy within 4 weeks or systemic therapy with radionucleotides within 6 weeks they are not eligible.
  • Participants who are receiving any other investigational agents, as well as cytotoxic or biological systemic anticancer therapy including investigational treatments within 4 weeks of initiating study treatment are excluded.
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  • Concomitant anticoagulation with oral anticoagulants (eg, warfarin, direct thrombin inhibitors) and platelet inhibitors (eg, clopidogrel).
  • Allowed anticoagulants are the following:
  • Prophylactic use of low-dose aspirin for cardio-protection (per local applicable guidelines) and low-dose low molecular weight heparins (LMWH).
  • Therapeutic doses of LMWH or anticoagulation with direct factor Xa inhibitors rivaroxaban, edoxaban, or apixaban in subjects without known brain metastases who are on a stable dose of the anticoagulant for at least 1 week before first dose of study treatment without clinically significant hemorrhagic complications from the anticoagulation regimen.
  • Note: Subjects must have discontinued oral anticoagulants within 3 days or 5 half-lives prior to first dose of study treatment, whichever is longer.
  • Any complementary medications (eg, herbal supplements or traditional Chinese medicines) to treat the disease under study within 2 weeks before first dose of study treatment.
  • The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
  • Unstable of deteriorating cardiovascular disorders • Congestive heart failure New York Heart Association Class 3 or 4, unstable angina pectoris, new-onset angina, serious cardiac arrhythmias (eg, ventricular flutter, ventricular fibrillation, Torsade's de pointes).
  • Uncontrolled hypertension defined as sustained blood pressure (BP) > 140 mm Hg systolic or > 90 mm Hg diastolic despite optimal antihypertensive treatment.
  • Stroke (including transient ischemic attack [TIA]), myocardial infarction, or other clinically significant arterial thrombotic and/or ischemic event within 6 months before first dose of study treatment.
  • Pulmonary embolism (PE) or deep vein thrombosis (DVT) or prior clinically significant venous events within 3 months before first dose of study treatment.
  • Note: Subjects with a diagnosis of DVT within 6 months are allowed if asymptomatic and stable at screening and are on a stable dose of the anticoagulant for at least 1 week before first dose of study treatment without clinically significant hemorrhagic complications from the anticoagulation regimen.
  • Note: Subjects who don't require prior anticoagulation therapy may be eligible but must be discussed and approved by the Principal Investigator.
  • o Prior history of myocarditis.
  • Gastrointestinal (GI) disorders including those associated with a high risk of perforation or fistula formation:
  • Tumors invading the GI-tract from external viscera.
  • Active peptic ulcer disease, inflammatory bowel disease, diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, or acute pancreatitis.
  • Acute obstruction of the bowel, gastric outlet, or pancreatic or biliary duct within 6 months before first dose unless cause of obstruction is definitively managed and subject is asymptomatic.
  • Abdominal fistula, gastrointestinal perforation, bowel obstruction, or intra-abdominal abscess within 6 months before first dose. Note: Complete healing of an intra-abdominal abscess must be confirmed before first dose of study treatment.
  • Known gastric or esophageal varices.
  • Ascites, pleural effusion, or pericardial fluid requiring drainage in last 4 weeks.
  • Clinically significant hematuria, hematemesis, or hemoptysis of > 0.5 teaspoon (2.5 ml) of red blood, or other history of significant bleeding (eg, pulmonary hemorrhage) within 12 weeks before first dose of study treatment.
  • Symptomatic cavitating pulmonary lesion(s) or endobronchial disease (asymptomatic or radiated lesions allowed).
  • Tumors invading major blood vessel including, but not limited to, inferior vena cava, pulmonary artery, or aorta. Note: Subjects with intravascular tumor extension (eg, tumor thrombus in renal vein or inferior vena cava) may be eligible following Principal Investigator approval.
  • Other clinically significant disorders that would preclude safe study participation.
  • Active infection requiring systemic treatment. Note: Prophylactic antimicrobial treatments (antibiotics, antimycotic, antiviral) are allowed.
  • Serious non-healing wound/ulcer/bone fracture. Note: non-healing wounds or ulcers are permitted if due to tumor-associated skin lesions.
  • Malabsorption syndrome.
  • Pharmacologically uncompensated, symptomatic hypothyroidism.
  • Moderate to severe hepatic impairment (Child-Pugh B or C).
  • Requirement for hemodialysis or peritoneal dialysis.
  • History of solid organ or allogeneic stem cell transplant.
  • Participants with brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression for at least 3 months.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to zanzalintinib or pembrolizumab or other agents used in study.
  • Moderate or strong CYP3A4 inhibitors (see section 5.4).
  • Human immunodeficiency virus (HIV)-infected participants on effective anti-retroviral therapy with undetectable viral load and CD4+ T cell count ≥ 200/µL within 6 months are eligible for this trial.
  • Note: To be eligible, participants taking CYP inhibitors (eg, zidovudine, ritonavir, cobicistat, didanosine) or CYP3 inducers (efavirenz) must change to a different regimen not including these drugs 7 days prior to initiation of study treatment. Anti-retroviral therapies (ART) must have been received for at least 4 weeks prior to the first dose. Note: CD4+ T cell counts, and viral load are monitored per standard of care by the local health care provider.
  • Participants with psychiatric illness/social situations that would limit compliance with study requirements.
  • Pregnant women are excluded from this study because zanzalintinib has the potential for teratogenic or abortifacient effects based on its mechanism of action. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with zanzalintinib and pembrolizumab, breastfeeding should be discontinued if the mother is treated with either agent. These potential risks may also apply the other agents used in this study.
  • Major surgery (as defined in Appendix 2) within 8 weeks prior to first dose of study treatment. Prior laparoscopic surgeries (ie nephrectomy) within 4 weeks prior to first dose of study treatment. Minor surgery (eg, simple excision, tooth extraction) within 5 days before first dose of study treatment. Complete wound healing from major or minor surgery must have occurred at least prior to first dose of study treatment.
  • Note: Fresh tumor biopsies should be performed at least 5 days before the first dose of study treatment. Subjects with clinically relevant ongoing complications from prior surgical procedures, including biopsies, are not eligible.
  • Corrected QT interval calculated by the Fridericia formula (QTcF) > 480 ms within 14 days per electrocardiogram (ECG) before first dose of study treatment.
  • Note: Triplicate ECG evaluations one minute apart will be performed and the average of these 3 consecutive results for QTcF will be used to determine eligibility.
  • Inability to swallow tablets or ingest a suspension either orally or by a nasogastric (NG) or gastrostomy (PEG) tube.
  • Another malignancy that requires active therapy and in the opinion of the Investigator would interfere with monitoring of radiologic assessments of response to Investigational Product, within 2 years before first dose of study treatment, except for superficial skin cancers, or localized, low-grade tumors deemed cured and not treated with systemic therapy. Incidentally diagnosed prostate cancer is allowed if assessed as stage ≤ T2N0M0 and Gleason score ≤ 6.
  • Suspected autoimmune disease, or active or prior documented autoimmune disease within the last 2 years.
  • Note: Subjects with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
  • Known positive test for tuberculosis infection if supported by clinical or radiographic evidence of disease.
  • History of idiopathic pulmonary fibrosis, organizing pneumonia (eg, bronchiolitis obliterans), drug induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computerized tomography (CT) scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
  • Free thyroxine (FT4) outside the laboratory normal reference range. Asymptomatic subjects with FT4 abnormalities can be eligible after Principal Investigator approval.
  • Diagnosis of immunodeficiency or is receiving systemic steroid therapy (> 10 mg daily prednisone equivalent) or any other form of immunosuppressive therapy within 2 weeks prior to first dose of study treatment. Inhaled, intranasal, intraarticular, and topical corticosteroids and mineralocorticoids are allowed. Note: Adrenal replacement steroid doses > 10 mg daily prednisone equivalent are permitted in the absence of active autoimmune disease. Transient short-term use of higher doses of systemic corticosteroids for allergic conditions (eg, contrast allergy) is also allowed.
  • Administration of a live, attenuated vaccine within 30 days before first dose of study treatment.
  • Other conditions, which in the opinion of the Investigator, would compromise the safety of the participant or the participant's ability to complete the study.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Michael S Nakazawa, MD contact

(713) 410-3409

msnakazawa@mdanderson.org

United States1 site, 1 recruiting

  • MD Anderson Cancer Center

    Houston, Texas, 77030

    Michael S Nakazawa, MD, 713-410-3409, msnakazawa@mdanderson.org

    Michael S Nakazawa, MD

    Recruiting

Other trials in United States

About this study

To learn if zanzalintinib and pembrolizumab can help to control select subtypes of advanced/metastatic soft-tissue sarcoma (UPS, MFS, HGPS, and HGUS

Read the detailed description

Primary Objectives

  1. To estimate the progression free survival (PFS), defined as the time from enrollment to time of first event (progressive disease per RECIST v.1.1 criteria or death from any cause) after receiving zanzalintinib and pembrolizumab or date of last contact for participants without an event

Secondary Objectives

  1. To estimate the progression free rate (progressive disease per RECIST v.1.1 criteria70 or death from any cause after first drug) at 6 months and 1 year
  2. To estimate the overall response rate (ORR) as measured by RECIST v1.1 a
  3. To describe the toxicity of zanzalintinib and pembrolizumab, defined by the rate of Grade 3 or higher adverse events by CTCAE v5 criteria
Being tested
Zanzalintinib, Pembrolizumab
Medical subject headings
Neoplasm Metastasis, Sarcoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT07283731
Study groupRoleWhat they receive
Single ArmExperimentalTreatment with Zanzalintinib + Pembrolizumab
Receives: Drug: Zanzalintinib; Drug: Pembrolizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: Through study completion; an average of 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Dec 2025
  2. Study start14 Apr 2026
  3. Primary completion1 Nov 2028 (estimated)
  4. Study completion1 Nov 2030 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
20 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07283731
Sponsor's protocol ID
2025-0952
Other IDs
NCI-2025-09246
Status last verified
Oct 2026
First submitted
12 Dec 2025
Last updated
2 Nov 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Zanzalintinib and Pembrolizumab in people with Phase 2 and Zanzalintinib, run by M.D. Anderson Cancer Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 0 inclusion and 59 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 2 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Michael S Nakazawa, MD ((713) 410-3409, msnakazawa@mdanderson.org), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety and adverse events (AEs) (time frame: Through study completion; an average of 1 year). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07283731.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Nov 2026.

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