Metastatic Soft-tissue SarcomaPhase 1NCT06968988
Zanzalintinib in Combination With Ipilimumab and Nivolumab in Patients With Metastatic Soft Tissue Sarcoma
A Phase 1 study testing Zanzalintinib, Ipilimumab and Nivolumab in people with Metastatic Soft-tissue Sarcoma, run by Washington University School of Medicine at 1 site in United States.
Trial summary
The investigators hypothesize that zanzalintinib in combination with ipilimumab and nivolumab will be well tolerated and serve as a potential therapeutic strategy in metastatic soft tissue sarcoma (mSTS) including myxofibrosarcoma, undifferentiated pleomorphic sarcoma, dedifferentiated liposarcoma, cutaneous… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Soft-tissue Sarcoma
- What is being tested?
- Zanzalintinib, Ipilimumab and Nivolumab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteUnited States
- Study dates
- 5 Jan 2026to 31 Jan 2034
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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
- Histologically or cytologically confirmed soft tissue sarcoma that is metastatic or unresectable.
- Must have received at least one but no more than 3 lines of therapy in the metastatic setting. Neoadjuvant or adjuvant therapy completed more than one year prior does not count towards as a line of therapy in the metastatic. Individuals with alveolar soft part sarcoma may enroll without being refractory to at least one line of therapy.
- Measurable disease per RECIST 1.1.
- At least 18 years of age.
- ECOG performance status ≤ 1.
- Adequate bone marrow and organ function as defined below:
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- Absolute neutrophil count (ANC) ≥ 1.5 K/cumm without granulocyte colony-stimulating factor support within 2 weeks prior to screening laboratory collection
- Platelets ≥ 100 K/cumm without transfusion within 2 weeks prior to screening laboratory collection
- Hemoglobin ≥ 9.0 g/dL without transfusion within 2 weeks prior to screening laboratory collection
- INR ≤ 1.5 and aPTT ≤ 1.2 x IULN. For subjects on Factor Xa inhibitors, criteria does not apply.
- Total bilirubin ≤ 1.5 x IULN (for subjects with Gilbert's disease ≤ 3 x IULN)
- AST(SGOT), ALT(SGPT), and alkaline phosphatase (ALP) ≤ 3.0 x IULN. For subjects with documented bone metastasis, ALP ≤ 5.0 x IULN.
- Serum albumin ≥ 2.8 g/dL.
- Calculated creatinine clearance ≥ 40 mL/min by Cockcroft-Gault.
- UPCR ≤ 1 mg/mg (≤ 113.2 mg/mmol) creatinine.
- Recovery to baseline or ≤ grade 1 from AEs, including immune-related AEs related to any prior treatments, unless AEs are clinically nonsignificant and/or stable on supportive therapy (e.g., physiological replacement of corticosteroid). Low-grade or controlled toxicities such as alopecia, ≤ grade 2 hypomagnesemia, ≤ grade 2 neuropathy are permitted.
- Sexually active fertile subjects and their partners must agree to use highly effective method of contraception during the course of the study and for the following durations after the last dose of treatment (whichever is later). An additional contraceptive method, such as a barrier method (eg, condom), is required. In addition, men must agree not to donate sperm and women must agree not to donate eggs (ova, oocyte) for the purpose of reproduction during these same periods:
- 186 days after last dose of zanzalintinib (for women) or 96 days after last dose of zanzalintinib (for men).
- 5 months after the last dose of nivolumab or 3 months after the last dose of ipilimumab.
- Female subjects of childbearing potential must not be pregnant at screening. Female subjects are considered to be of childbearing potential unless one of the following criteria is met: permanent sterilization (hysterectomy, bilateral salpingectomy, or bilateral oophorectomy) or documented postmenopausal status (defined as 12 months of amenorrhea in a woman > 45 years-of-age in the absence of other biological or physiological causes. In addition, females < 55 years-of-age must have a serum follicle stimulating hormone [FSH] level > 40 mIU/mL to confirm menopause). Note: Documentation may include review of medical records, medical examination, or medical history interview by study site staff.
- Ability to understand and willingness to sign an IRB approved written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants.
Who cannot join
- Translocation-driven sarcoma except for ASPS.
- Prior treatment with zanzalintinib, cabozantinib, PD-1 inhibitor (eg, cemiplimab, nivolumab, pembrolizumab), PD-L1 inhibitor (eg, atezolizumab, avelumab, durvalumab), or CTLA-4 inhibitor (eg, ipilimumab).
- Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 2 weeks before first dose of study treatment.
- Receipt of any type of cytotoxic, biologic, or other systemic anticancer therapy (including investigational) within 4 weeks before first dose of study treatment.
- Radiation therapy for bone metastasis within 2 weeks before first dose of study treatment; any other radiation therapy within 4 weeks before first dose of study treatment. Systemic treatment with radionuclides within 6 weeks before first dose of study treatment. Subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible.
- Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 4 weeks before first dose of study treatment. Note: Eligible subjects must be neurologically asymptomatic and without corticosteroid treatment at the time of enrollment. Note: Base of skull lesions without definitive evidence of dural or brain parenchymal involvement are allowed.
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- A history of allergic reactions attributed to compounds of similar chemical or biologic composition to zanzalintinib, ipilimumab, nivolumab, or other agents used in the study.
- Concomitant anticoagulation with warfarin or other vitamin-K antagonists, direct thrombin inhibitors, or antiplatelet agents (e.g. 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 (e.g. herbal supplements or traditional Chinese medicines) to treat the disease under study within 2 weeks before first dose of study treatment.
- Uncontrolled, significant intercurrent or recent illness including, but not limited to:
- Unstable or deteriorating cardiovascular disorders:
- Congestive heart failure NYHA Class 3 or 4, or Class 2 or higher unstable angina pectoris, new-onset angina, serious cardiac arrhythmias (e.g. ventricular flutter, ventricular fibrillation, Torsades de pointes).
- Uncontrolled hypertension defined as sustained blood pressure > 140 mmHg systolic or > 90 mmHg diastolic despite optimal antihypertensive treatment.
- Stroke (including transient ischemic attack), myocardial infarction, or other clinically significant arterial thrombotic and/or ischemic event within 6 months before first dose of study treatment.
- Pulmonary embolism or deep vein thrombosis 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 PI.
- Prior history of myocarditis.
- Gastrointestinal 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 (e.g. pulmonary hemorrhage) within 12 weeks before first dose of study treatment.
- Symptomatic cavitating pulmonary lesion(s) or endobronchial disease (asymptomatic or radiated lesions allowed).
- Lesions invading major blood vessel including, but not limited to, inferior vena cava, pulmonary artery, or aorta. Note: subjects with intravascular tumor extension (e.g. tumor thrombus in renal vein on inferior vena cava) may be eligible following PI approval.
- Other clinically significant disorders that would preclude safe study participation, in the opinion of the investigator. Specific conditions are noted below:
- Active infection requiring systemic treatment. Note: prophylactic antimicrobial treatments (antibiotics, antimycotics, antivirals) are allowed.
- Known infection with acute or chronic hepatitis B or C, known HIV or AIDS-related illness except for subjects meeting all of the following criteria:
- On stable anti-retroviral therapy
- CD4+ T cell count ≥ 200/μL
- Undetectable viral load. Note: HIV testing will be performed at screening if and as required by local regulation. Note: to be eligible, participants taking CYP inhibitors (e.g. zidovudine, ritonavir, cobicistat, didanosine) orCYP3 inducers (efavirenz) must change to a different regimen not including these drugs 7 days prior to initiation of study treatment. Anti-retroviral therapies 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 provider.
- 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.
- Major surgery (e.g. GI surgery, removal or biopsy of brain metastasis) within 8 weeks prior to first dose of study treatment. Prior laparoscopic surgeries (e.g. nephrectomy) within 4 weeks prior to first dose of study treatment. Minor surgery (e.g. 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 ECG before first dose of study treatment. Note: triplicate ECG evaluations will be performed and the average of these 3 consecutive results for QTcF will be used to determine eligibility.
- History of psychiatric illness likely to interfere with ability to comply with protocol requirements or give informed consent.
- Pregnant and/or breastfeeding. Women of childbearing potential must have a negative serum pregnancy test within 14 days of study entry.
- Inability to swallow tablets or ingest a suspension either orally or by a NG or 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 study treatment, 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
- Any active, known, or suspected autoimmune disease. 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, or 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Washington University School of Medicine
St Louis, Missouri, 63110
About this study
Official title: Phase I Study With Expansion Cohort of Zanzalintinib in Combination With Ipilimumab and Nivolumab in Patients With Metastatic Soft Tissue Sarcoma
The investigators hypothesize that zanzalintinib in combination with ipilimumab and nivolumab will be well tolerated and serve as a potential therapeutic strategy in metastatic soft tissue sarcoma (mSTS) including myxofibrosarcoma, undifferentiated pleomorphic sarcoma, dedifferentiated liposarcoma, cutaneous angiosarcoma, and undifferentiated sarcoma histologies.
- Conditions
- Metastatic Soft-tissue Sarcoma
- Being tested
- Zanzalintinib, Ipilimumab, Nivolumab
- Keywords
- Soft Tissue Sarcoma, Zanzalintinib, Immunotherapy, Nivolumab, Ipilimumab
- Medical subject headings
- Sarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ZanzalintinibDrug
Also called XL092
Zanzalintinib will be supplied by Exelixis, Inc.
IpilimumabDrug
Also called Yervoy
Ipilimumab will be commercially sourced.
NivolumabDrug
Also called Opdivo
Nivolumab will be commercially sourced.
| Study group | Role | What they receive |
|---|---|---|
| Dose Escalation Dose Level 1 (starting dose): Zanzalintinib + Nivolumab + Ipilimumab | Experimental | Zanzalintinib 40 mg by mouth once per day is self administered daily, and nivolumab 3 mg/kg intravenously and ipilimumab 1 mg/kg intravenously are administered intravenously every 3 weeks for a total of 4 doses. After completion of the first 4 cycles, ipilimumab is discontinued while nivolumab 480 mg intravenously is continued every 4 weeks in combination with daily zanzalintinib. Receives: Drug: Zanzalintinib; Drug: Ipilimumab; Drug: Nivolumab |
| Dose Escalation Dose Level 2: Zanzalintinib + Nivolumab + Ipilimumab | Experimental | Zanzalintinib 60 mg by mouth once per day is self administered daily, and nivolumab 3 mg/kg intravenously and ipilimumab 1 mg/kg intravenously are administered intravenously every 3 weeks for a total of 4 doses. After completion of the first 4 cycles, ipilimumab is discontinued while nivolumab 480 mg intravenously is continued every 4 weeks in combination with daily zanzalintinib. Receives: Drug: Zanzalintinib; Drug: Ipilimumab; Drug: Nivolumab |
| Dose Escalation Dose Level -1: Zanzalintinib + Nivolumab + Ipilimumab | Experimental | Zanzalintinib 20 mg by mouth once per day is self administered daily, and nivolumab 3 mg/kg intravenously and ipilimumab 1 mg/kg intravenously are administered intravenously every 3 weeks for a total of 4 doses. After completion of the first 4 cycles, ipilimumab is discontinued while nivolumab 480 mg intravenously is continued every 4 weeks in combination with daily zanzalintinib. Receives: Drug: Zanzalintinib; Drug: Ipilimumab; Drug: Nivolumab |
| Expansion: Zanzalintinib + Nivolumab + Ipilimumab | Experimental | Zanzalintinib dose determined in Dose Escalation by mouth once per day is self administered daily, and nivolumab 3 mg/kg intravenously and ipilimumab 1 mg/kg intravenously are administered intravenously every 3 weeks for a total of 4 doses. After completion of the first 4 cycles, ipilimumab is discontinued while nivolumab 480 mg intravenously is continued every 4 weeks in combination with daily zanzalintinib. Receives: Drug: Zanzalintinib; Drug: Ipilimumab; Drug: Nivolumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Occurrence of dose-limiting toxicities (DLTs)
DLTs are defined in the protocol.
Measured: Through day 42
Secondary outcomes (5)
Frequency and grades of treatment-emergent adverse events (TEAEs)
Graded per CTCAE v5.0.
Measured: From start of treatment through 100 days after completion of treatment (estimated to be 24 months and 100 days)
Rate of treatment discontinuation due to treatment-emergent adverse events (TEAEs)
Measured: From start of treatment through completion of treatment (estimated to be 24 months)
Objective response rate (ORR) per RECIST 1.1 criteria
- Objective response (OR) is defined as number of participants with complete response (CR) or partial response (PR).
- Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Disappearance of all non-target lesions and normalization of tumor marker level.
- Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
Measured: Through completion of treatment (estimated to be 24 months)
Clinical benefit rate (CBR) per RECIST 1.1 criteria
- Clinical benefit is defined complete response (CR), partial response (PR) or stable disease (SD) for 6 weeks.
- Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Disappearance of all non-target lesions and normalization of tumor marker level.
- Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
- Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
Measured: Through completion of treatment (estimated to be 24 months)
Duration of response (DoR)
- DOR is time from treatment initiation to disease progression or death as a first event for patients who achieve a complete response (CR) or partial response (PR).
- Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Disappearance of all non-target lesions and normalization of tumor marker level.
- Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
Measured: Through completion of follow-up (estimated to be 60 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 May 2025
- Study start5 Jan 2026
- Primary completion12 Feb 2029 (estimated)
- Study completion31 Jan 2034 (estimated)
Why it stopped: Protocol amendment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Soft-tissue SarcomaStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 18 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- Exelixis
- Responsible party
- Sponsor
- Investigators
- Mia Weiss, M.D., Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06968988
- Sponsor's protocol ID
- 202507090
- Status last verified
- Sep 2026
- First submitted
- 5 May 2025
- Last updated
- 4 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Deidentified individual participant data (IPD) underlying the results reported in this article, including text, tables, figures, and appendices, will be made available. In addition, the study protocol, statistical analysis plan, and informed consent form will be available.
Study at a glance
From the registry record, last updated by the sponsor on 4 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study With Expansion Cohort of Zanzalintinib in Combination With Ipilimumab and Nivolumab in Patients With Metastatic Soft Tissue Sarcoma
- ClinicalTrials.gov ID
- NCT06968988
- Acronym / sponsor ID
- 202507090
- Conditions
- Metastatic Soft-tissue Sarcoma
- Keywords
- Soft Tissue Sarcoma, Zanzalintinib, Immunotherapy, Nivolumab, Ipilimumab
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- SuspendedReason stopped: Protocol amendment
- Enrolment
- 18 participants (estimated)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Collaborators
- Exelixis
- Study start
- 5 Jan 2026 (actual)
- Primary completion
- 12 Feb 2029 (estimated)
- Study completion
- 31 Jan 2034 (estimated)
- First posted
- 13 May 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The investigators hypothesize that zanzalintinib in combination with ipilimumab and nivolumab will be well tolerated and serve as a potential therapeutic strategy in metastatic soft tissue sarcoma (mSTS) including myxofibrosarcoma, undifferentiated pleomorphic sarcoma, dedifferentiated liposarcoma, cutaneous angiosarcoma, and undifferentiated sarcoma histologies.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Dose Escalation Dose Level 1 (starting dose): Zanzalintinib + Nivolumab + Ipilimumab | Experimental | Drug: Zanzalintinib, Drug: Ipilimumab, Drug: NivolumabZanzalintinib 40 mg by mouth once per day is self administered daily, and nivolumab 3 mg/kg intravenously and ipilimumab 1 mg/kg intravenously are administered intravenously every 3 weeks for a total of 4 doses. After completion of the first 4 cycles, ipilimumab is discontinued while nivolumab 480 mg intravenously is continued every 4 weeks in combination with daily zanzalintinib. |
| Dose Escalation Dose Level 2: Zanzalintinib + Nivolumab + Ipilimumab | Experimental | Drug: Zanzalintinib, Drug: Ipilimumab, Drug: NivolumabZanzalintinib 60 mg by mouth once per day is self administered daily, and nivolumab 3 mg/kg intravenously and ipilimumab 1 mg/kg intravenously are administered intravenously every 3 weeks for a total of 4 doses. After completion of the first 4 cycles, ipilimumab is discontinued while nivolumab 480 mg intravenously is continued every 4 weeks in combination with daily zanzalintinib. |
| Dose Escalation Dose Level -1: Zanzalintinib + Nivolumab + Ipilimumab | Experimental | Drug: Zanzalintinib, Drug: Ipilimumab, Drug: NivolumabZanzalintinib 20 mg by mouth once per day is self administered daily, and nivolumab 3 mg/kg intravenously and ipilimumab 1 mg/kg intravenously are administered intravenously every 3 weeks for a total of 4 doses. After completion of the first 4 cycles, ipilimumab is discontinued while nivolumab 480 mg intravenously is continued every 4 weeks in combination with daily zanzalintinib. |
| Expansion: Zanzalintinib + Nivolumab + Ipilimumab | Experimental | Drug: Zanzalintinib, Drug: Ipilimumab, Drug: NivolumabZanzalintinib dose determined in Dose Escalation by mouth once per day is self administered daily, and nivolumab 3 mg/kg intravenously and ipilimumab 1 mg/kg intravenously are administered intravenously every 3 weeks for a total of 4 doses. After completion of the first 4 cycles, ipilimumab is discontinued while nivolumab 480 mg intravenously is continued every 4 weeks in combination with daily zanzalintinib. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- Histologically or cytologically confirmed soft tissue sarcoma that is metastatic or unresectable.
- Must have received at least one but no more than 3 lines of therapy in the metastatic setting. Neoadjuvant or adjuvant therapy completed more than one year prior does not count towards as a line of therapy in the metastatic. Individuals with alveolar soft part sarcoma may enroll without being refractory to at least one line of therapy.
- Measurable disease per RECIST 1.1.
- At least 18 years of age.
- ECOG performance status ≤ 1.
Key exclusion criteria (52 listed)
- Translocation-driven sarcoma except for ASPS.
- Prior treatment with zanzalintinib, cabozantinib, PD-1 inhibitor (eg, cemiplimab, nivolumab, pembrolizumab), PD-L1 inhibitor (eg, atezolizumab, avelumab, durvalumab), or CTLA-4 inhibitor (eg, ipilimumab).
- Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 2 weeks before first dose of study treatment.
- Receipt of any type of cytotoxic, biologic, or other systemic anticancer therapy (including investigational) within 4 weeks before first dose of study treatment.
- Radiation therapy for bone metastasis within 2 weeks before first dose of study treatment; any other radiation therapy within 4 weeks before first dose of study treatment. Systemic treatment with radionuclides within 6 weeks before first dose of study treatment. Subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ZanzalintinibAlso: XL092Zanzalintinib will be supplied by Exelixis, Inc. | Drug | Dose Escalation Dose Level -1: Zanzalintinib + Nivolumab + Ipilimumab, Dose Escalation Dose Level 1 (starting dose): Zanzalintinib + Nivolumab + Ipilimumab, Dose Escalation Dose Level 2: Zanzalintinib + Nivolumab + Ipilimumab, Expansion: Zanzalintinib + Nivolumab + Ipilimumab |
| IpilimumabAlso: YervoyIpilimumab will be commercially sourced. | Drug | Dose Escalation Dose Level -1: Zanzalintinib + Nivolumab + Ipilimumab, Dose Escalation Dose Level 1 (starting dose): Zanzalintinib + Nivolumab + Ipilimumab, Dose Escalation Dose Level 2: Zanzalintinib + Nivolumab + Ipilimumab, Expansion: Zanzalintinib + Nivolumab + Ipilimumab |
| NivolumabAlso: OpdivoNivolumab will be commercially sourced. | Drug | Dose Escalation Dose Level -1: Zanzalintinib + Nivolumab + Ipilimumab, Dose Escalation Dose Level 1 (starting dose): Zanzalintinib + Nivolumab + Ipilimumab, Dose Escalation Dose Level 2: Zanzalintinib + Nivolumab + Ipilimumab, Expansion: Zanzalintinib + Nivolumab + Ipilimumab |
Primary outcome
Occurrence of dose-limiting toxicities (DLTs)
Time frame: Through day 42
DLTs are defined in the protocol.
5 secondary outcomes
Frequency and grades of treatment-emergent adverse events (TEAEs)
Time frame: From start of treatment through 100 days after completion of treatment (estimated to be 24 months and 100 days)
Rate of treatment discontinuation due to treatment-emergent adverse events (TEAEs)
Time frame: From start of treatment through completion of treatment (estimated to be 24 months)
Objective response rate (ORR) per RECIST 1.1 criteria
Time frame: Through completion of treatment (estimated to be 24 months)
Clinical benefit rate (CBR) per RECIST 1.1 criteria
Time frame: Through completion of treatment (estimated to be 24 months)
Duration of response (DoR)
Time frame: Through completion of follow-up (estimated to be 60 months)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Sep 2026.
- Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of MedicineLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Deidentified individual participant data (IPD) underlying the results reported in this article, including text, tables, figures, and appendices, will be made available. In addition, the study protocol, statistical analysis plan, and informed consent form will be available.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mia Weiss, M.D. principal investigator
Washington University School of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Zanzalintinib, Ipilimumab and Nivolumab in people with Metastatic Soft-tissue Sarcoma, run by Washington University School of Medicine 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 21 inclusion and 52 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: paused, as of the sponsor's last update on 4 Sep 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Occurrence of dose-limiting toxicities (DLTs) (time frame: Through day 42). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 4 Sep 2026.