Cabozantinib and Dostarlimab in Recurrent Gynecologic Carcinosarcoma

Exclusion Criteria

• •1. Prior treatment with cabozantinib.
• •2. Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 2 weeks or 5 half-lives (whichever is longer) before first dose of study treatment.
• •3. Receipt of any type of cytotoxic, biologic, or other systemic anticancer therapy (including investigational) within 4 weeks before first dose of study treatment.
• •5. 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. Eligible patients must be neurologically asymptomatic and without corticosteroid treatment at the time of first dose of study treatment.
• •6. Concomitant anticoagulation with coumarin agents (e.g., warfarin), direct thrombin inhibitors (e.g., dabigatran), direct factor Xa inhibitor betrixabin, or platelet inhibitors (e.g., clopidogrel). Allowed anticoagulants are the following:
• •1. Prophylactic use of low-dose aspirin for cardio-protection (per local applicable guidelines) and low-dose low molecular weight heparins (LMWH).
• •2. 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 or the tumor.
• •7. The patient has prothrombin time (PT)/INR or partial thromboplastin time (PTT) test ≥ 1.3 X the laboratory ULN within 7 days before the first dose of study treatment.
• •8. The patient has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
• •a. Cardiovascular disorders: i. Congestive heart failure New York Heart Association Class 3 or 4, unstable angina pectoris, serious cardiac arrhythmias.
• •ii. Uncontrolled hypertension defined as sustained blood pressure (BP) \> 140 mm Hg systolic or \> 90 mm Hg diastolic despite optimal antihypertensive treatment.
• •iii. Stroke (including transient ischemic attack \[TIA\]), myocardial infarction (MI), or other ischemic event, or thromboembolic event (e.g., deep venous thrombosis, pulmonary embolism) within 6 months before first dose.
• •b. Gastrointestinal (GI) disorders including those associated with a high risk of perforation or fistula formation: i. The patient has evidence of tumor invading the GI tract, active peptic ulcer disease, inflammatory bowel disease (e.g., Crohn's disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, acute pancreatitis, acute obstruction of the pancreatic duct or common bile duct, or gastric outlet obstruction.
• •ii. Abdominal fistula, GI 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.
• •c. 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.
• •d. Cavitating pulmonary lesion(s) or known endotracheal or endobronchial disease manifestation.
• •e. Lesions invading or encasing any major blood vessels. f. Other clinically significant disorders that would preclude safe study participation.
• •i. Serious non-healing wound/ulcer/bone fracture ii. Uncompensated/symptomatic hypothyroidism (i.e. inadequately treated hypothyroidism) iii. Moderate to severe hepatic impairment (Child-Pugh B or C)
• •10. Corrected QT interval calculated by the Fridericia formula (QTcF) \> 500 ms per electrocardiogram (ECG) within 28 days before first dose of study treatment \[add reference for Fridericia formula\].
• •Note: If a single ECG shows a QTcF with an absolute value \> 500 ms, two additional ECGs at intervals of approximately 3 min must be performed within 30 min after the initial ECG, and the average of these three consecutive results for QTcF will be used to determine eligibility.
• •11. Inability to swallow tablets.
• •12. Previously identified allergy or hypersensitivity to components of the study treatment formulations.
• •13. Diagnosis of another malignancy 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.
• •14. Patients with concurrent cytotoxic chemotherapy or radiation therapy are excluded.
• •15. Patients with a serious chronic or acute illness, such as cardiac disease (NYHA class III or IV), hepatic disease, or other illness considered by the Principal Investigator as unwarranted high risk for investigational drug treatment.
• •16. Patients with a medical or psychological impediment to probable compliance with the protocol should be excluded.
• •17. Presence of a known active acute or chronic infection including: a urinary tract infection, HIV or viral hepatitis; however, it is acceptable to treat an acute infection and then re-screen or re-evaluate eligibility.
• •18. Administration of a live, attenuated vaccine within 30 days prior to first dose of study treatment
• •19. Other clinically significant disorders:
• •1. History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan.
• •2. Active, known, or suspected autoimmune disease (exceptions: type 1 diabetes mellitus, hypothyroidism, skin disorders, conditions not expected to recur in the absence of an external trigger)
• •3. Malabsorption syndrome
• •4. Requirement for hemodialysis or peritoneal dialysis
• •5. History of solid organ or allogenic stem cell transplant