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New treatment option for Phase 2
Official title Phase 2 Trial of Zanzalintinib and Pembrolizumab in Select Subtypes of Advanced/Metastatic Soft-tissue Sarcoma
ClinicalTrials.gov ID: NCT07283731
What this study is testing
What is Zanzalintinib?
Zanzalintinib is an investigational medicine, being studied as a potential treatment for phase 2.
Plain-language explanation of the investigational treatment - it is being studied and is not an approved or proven therapy. The study team can confirm the details.
- What it's testing
- To learn if zanzalintinib and pembrolizumab can help to control select subtypes of advanced/metastatic soft-tissue sarcoma (UPS, MFS, HGPS, and HGUS
- Phase 2: a mid-size study of how well it works
A plain-language read of the study's public ClinicalTrials.gov listing. The study team confirms the details.
Who can take part
Ages 18 and older
You may be able to join if
- Eligibility Criteria
- Participants must have histologically or cytologically confirmed undifferentiated pleomorphic sarcoma (UPS), myxofibrosarcoma (MFS), high grade...
- Participant ≥ 18 years of age. Because no dosing or adverse event data are currently available on the use of zanzalintinib in combination with...
- ECOG performance status ≤2 (Karnofsky ≥60%).
- Participants must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter...
You likely can't join if
- 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...
- Participants who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> Grade 1) with the...
- Participants with clinically relevant ongoing complications from prior radiation therapy are not eligible. Additionally, if participants have...
- Participants who are receiving any other investigational agents, as well as cytotoxic or biological systemic anticancer therapy including...
See the full eligibility criteria
Who can join
- Eligibility Criteria
- Participants must have histologically or cytologically confirmed undifferentiated pleomorphic sarcoma (UPS), myxofibrosarcoma (MFS), high grade pleomorphic (HGPS) or undifferentiated sarcoma (HGUS).
- Participant ≥ 18 years of age. Because no dosing or adverse event data are currently available on the use of zanzalintinib in combination with pembrolizumab in participants \<18 years of age, children are excluded from...
- ECOG performance status ≤2 (Karnofsky ≥60%).
- Participants must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal...
- At least 4 weeks since prior chemotherapy.
- At least 2 weeks since radiation therapy for bone metastases, any other radiation therapy within 4 weeks before first dose of study treatment. At least 6 weeks since systemic treatment with radionuclides before first...
- Participants must have adequate organ and marrow function as defined below within 14 days before first dose of study treatment: absolute neutrophil count ≥1,500/mcL without granulocyte colony-stimulating factor support...
- For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
- Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. For participants with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV...
- Participants with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression for at least 4 weeks. Note: Participants must have...
- Participants with new or progressive brain metastases (active brain metastases) or leptomeningeal disease are eligible if the treating physician determines that immediate CNS specific treatment is not required and is...
- Participants with a prior or concurrent malignancy whose natural history or treatment does not interfere with the safety or how well it works assessment of the investigational regimen are eligible for this trial.
- Participants with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association...
- The effects of zanzalintinib and pembrolizumab on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of...
- Females must not be pregnant.
- Approved methods of birth control are as follows: Hormonal contraception (i.e. birth control pills, injection, implant, transdermal patch, vaginal ring), intrauterine device (IUD), tubal ligation or hysterectomy...
- Women of childbearing potential must comply for the duration of study participation and through 186 days after the last dose of zanzalintinib and 180 days after the last dose of pembrolizumab, whichever date is later...
- Capable of understanding and complying with the protocol requirements and must have signed the informed consent document.
- Consent to MD Anderson companion laboratory protocol 2014-0938 for correlative analyses of biopsies obtained in this trial.
What rules you out
- 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...
- 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...
- 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 people without known brain metastases who are on a stable dose of the anticoagulant for at least 1 week...
- 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...
- 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: people with a diagnosis of DVT within 6 months are allowed...
- 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...
- 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...
- 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: people with intravascular tumor extension (eg, tumor thrombus in renal vein or inferior vena cava)...
- 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...
- 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...
- 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...
- 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...
- 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...
- Suspected autoimmune disease, or active or prior documented autoimmune disease within the last 2 years. Note: people with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such...
- 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...
- Free thyroxine (FT4) outside the laboratory normal reference range. Asymptomatic people 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...
- 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.
The study team makes the final eligibility decision.
Where it's taking place
- Houston, Texas, United States
Compensation & support
A stipend or compensation may be offered.
Compensation mentioned.
ClinicalTrials.gov doesn't provide a reliable structured field for payment or travel support - confirm details with the study team.
Questions & answers
Do participants get paid in this trial?
This study's listing includes signals that participants may be compensated or receive a stipend. Amounts vary and are set by the study team - confirm the details with them.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 18 years and older. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include Houston, Texas, United States. Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from ClinicalTrials.gov; the study team decides eligibility.