Zanzalintinib Plus Cemiplimab for the Treatment of BRAF Wild-Type Anaplastic Thyroid Cancer

Starting soon · Phase 2

Conditions studied: Anaplastic Thyroid Cancer

In brief

The goal of the trial is to improve this OS by 4 months (to 9.9 months) using the zanzalintinib + cemiplimab treatment combination. Given an accrual period of 24 months and a maximum follow-up time of 36 months, at the significance level of 0.1, to achieve the power of 0.8, the sample size needed is 24 patients and the number of events required is 17. These results are based on a one-sided test with exponential assumption for survival time.

Key facts

Study ID

NCT07470489

Run by

M.D. Anderson Cancer Center

People needed

12

Starts

2026-09-30

Expected to finish

2032-09-01

Last updated by the study team

2026-07-29

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Male/female participants who are at least 18 years of age on the day of signing informed consent
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2. Evaluation of ECOG is to be performed within 7 days prior to the date of allocation/randomization.
• Pathologic findings supporting the clinical impression of anaplastic thyroid carcinoma. Diagnosis may include consistent with or suggestive of terminology associated with anaplastic thyroid carcinoma, undifferentiated carcinoma, squamous carcinoma; carcinoma with spindled, giant cell, or epithelial features; poorly differentiated carcinoma with pleomorphism, extensive necrosis with tumor cells present.
• Patients deemed to have unresectable locoregional disease (stage IVB) or metastatic disease (stage IVC). Patients who are unwilling to undergo surgery or external beam radiation are also eligible.
• Patients with BRAF-wild type ATC will be eligible for this study. Patients with a BRAFV600E mutation who are unable to receive the FDA approved drugs, dabrafenib/trametinib, are also eligible as long as this is documented.
• Unless clinically contraindicated, all patients with active neck disease who have not received prior neck radiation will be considered for palliative-dose EBRT to the neck (preferably 14 Gy, but 7 to 30 Gy is acceptable) within one month prior to the initiation of study drugs. All patients eligible for palliative neck EBRT who do not undergo radiation will need to be discussed with the PI for study eligibility. In patients with unstable airway, an intervention to stabilize the airway must be implemented prior to enrollment.
• Patients must have adequate organ and marrow function, based upon meeting all the following laboratory criteria within 14 days before first dose of study treatment:
• Absolute neutrophil count (ANC) ≥ 1500/mm3 (≥ 1.5 GI/L) without granulocyte colonystimulating factor support within 2 weeks of screening laboratory sample collection.
• Platelets ≥ 100,000/mm3 (≥ 100 GI/L) without transfusion within 2 weeks of screening laboratory sample collection.
• Hemoglobin ≥ 9 g/dL (≥ 90 g/L) without transfusion within 2 weeks prior to screening laboratory sample collection.
• International Normalized Ratio (INR) ≤ 1.5 and activated partial thromboplastin time (aPTT) ≤ 1.2 x upper limit of normal (ULN).
• Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) ≤ 3 x ULN. For subjects with documented bone metastasis ALP ≤ 5 x ULN. For subjects with concurrent liver metastases, AST/ALT ≤ 5 x ULN
• Total bilirubin ≤ 1.5 x ULN (for subjects with Gilbert's disease ≤ 3 x ULN).
• Serum creatinine ≤ 1.5 x ULN or calculated creatinine clearance ≥ 40 mL/min (≥ 0.67 mL/sec) using the Cockcroft Gault equation. Urine protein-to-creatinine ratio (UPCR) ≤ 1 mg/mg (≤ 113.2 mg/mmol) creatinine.
• Capable of understanding and complying with the protocol requirements and must have signed the informed consent document.
• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
• Patients 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 Functional Classification. To be eligible for this trial, patients should be < class II.
• Sexually active fertile subjects and their partners must agree to use highly effective method of contraception (defined in Appendix A) during the course of the study for 186 days after the last dose of zanzalintinib or 4 months after the last dose of cemiplimab, whichever is later. 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.
• Women of childbearing potential (WOCBP) must not be pregnant at screening. Female subjects are considered to be of childbearing potential unless one of the following criteria is met:
• Postmenopausal, i.e.no menses in greater than or equal to 12 consecutive months 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
• History of hysterectomy or bilateral salpingo-oophorectomy.
• Ovarian failure (Follicle Stimulating Hormone and Estradiol in menopausal range, who have received Whole Pelvic Radiation Therapy).
• History of bilateral tubal ligation or another surgical sterilization procedure.

You may not qualify if…

• Prior treatment with zanzalintinib or any other multikinase inhibitor (e.g. lenvatinib, sorafenib, vandetanib, cabozantinib).
• Prior treatment with cemiplimab or any other immune checkpoint inhibitor or immunotherapy (e.g. anti-CTLA4, anti-PD-1, anti-PD-L1, BITEs).
• Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 2 weeks or 5 half-lives before first dose of study treatment, whichever is longer.
• Receipt of any type of cytotoxic, biologic or other systemic anticancer therapy (including investigational) within 4 weeks before first dose of study treatment
• Subjects with clinically relevant ongoing complications from prior radiation therapy that have not completely resolved (eg, radiation esophagitis or other inflammation of the viscera).
• 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.
• Concomitant anticoagulation with oral anticoagulants (e.g, warfarin, direct thrombin inhibitors) and platelet inhibitors (eg, clopidogrel), except:
• 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 (eg, warfarin, direct thrombin inhibitors) 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.
• Electrolyte abnormalities that have not been corrected, with the exception of calcium if oral calcium and calcitriol are being titrated.
• Free thyroxine (FT4) outside the laboratory normal reference range. Asymptomatic subjects with FT4 abnormalities can be eligible after Principal Investigator approval
• Subjects having > 2+ proteinuria on urine dipstick testing unless a 24-hour urine collection for quantitative assessment indicates that the urine protein is <1 g/24 hours.
• 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, class 2 or higher, unstable angina pectoris, new-onset angina, serious cardiac arrhythmias (eg, ventricular flutter, ventricular fibrillation, Torsades 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 12 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.
• 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

Where it is running

• MD Anderson Cancer Center — Houston, Texas, United States

Full record on ClinicalTrials.gov

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