Autologous Dendritic Cell Vaccine in Kidney Cancer

Inclusion Criteria:

1. Histologically proven clear cell renal cancer that is non-metastatic and amenable tosurgical resection with no evidence of metastatic disease or lesions outside of thekidney.

2. 18 years or older (male or female) with an ECOG performance status of 0 or 1.

3. Have serotype HLA-A2+ if receiving vaccine.

4. Capable of understanding and complying with the protocol requirements and havesigned the informed consent document.

5. Adequate organ and marrow function, based upon meeting all of the followinglaboratory criteria within 14 days before first dose of study treatment:

6. Absolute neutrophil count (ANC) ≥ 1500/µL without granulocyte colony-stimulating factor support.

7. White blood cell count ≥ 2500/µL.

8. Platelets ≥ 100,000/µL without transfusion.

9. Hemoglobin ≥ 9 g/dL (≥ 90 g/L).

10. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkalinephosphatase (ALP) ≤ 3x upper limit of normal (ULN). ALP ≤ 5x ULN withdocumented bone metastases.

11. Total bilirubin ≤ 1.5x ULN (for subjects with Gilbert's disease ≤ 3x ULN).

12. Serum albumin ≥ 2.8 g/dl

13. (PT)/INR or partial thromboplastin time (PTT) test < 1.3x the laboratory ULN

14. Serum creatinine ≤ 2.0 ULN or calculated creatinine clearance ≥ 30 mL/min (≥ 0.5 mL/sec) using the Cockcroft-Gault equation: Males: (140 - age) x weight (kg)/(serum creatinine [mg/dL] × 72) Females: [(140 - age) x weight (kg)/(serumcreatinine [mg/dL] × 72)] × 0.85

15. Urine protein/creatinine ratio (UPCR) ≤ 1 mg/mg (≤ 113.2 mg/mmol), or 24-hurine protein ≤ 1

16. Sexually active fertile subjects and their partners must agree to use medicallyaccepted methods of contraception (e.g., barrier methods, including male condom,female condom, or diaphragm with spermicidal gel) during the course of the study andfor 4 months after the last dose of study treatment.

17. Female subjects of childbearing potential must not be pregnant at screening. Femalesubjects are considered to be of childbearing potential unless one of the followingcriteria are met: documented permanent sterilization (hysterectomy, bilateralsalpingectomy, or bilateral oophorectomy) or documented postmenopausal status (defined as 12 months of amenorrhea in a woman > 45 years-of-age in the absence ofother biological or physiological causes. In addition, females < 55 years-of-agemust have a serum follicle stimulating (FSH) level > 40 mIU/mL to confirmmenopause). Note: Documentation may include review of medical records, medicalexaminations, or medical history interview by study site.

Exclusion Criteria:

1. Current (within the preceding 6 weeks) treatment with systemic immunosuppressiveagents including steroids except when they are administered as replacement therapyfor endocrine dysfunction and do not exceed 10 mg prednisone or equivalent daily.

2. Known or suspected metastatic disease.

3. Active Hepatitis B or Hepatitis C infection or any other active infection requiringintravenous therapy.

4. Blood transfusion within two weeks prior to leukapheresis.

5. Prior treatment with cabozantinib.

6. Receipt of any type of small molecule kinase inhibitor (including investigationalkinase inhibitor) within two weeks before first dose of study treatment.

7. Receipt of any type of cytotoxic, biologic or other systemic anticancer therapy (including investigational) within four weeks before first dose of study treatment.

8. Radiation therapy for bone metastasis within 2 weeks or any other radiation therapywithin 4 weeks before first dose of study treatment. Systemic treatment withradionuclides within 6 weeks before first dose of study treatment. Subjects withclinically relevant ongoing complications from prior radiation therapy are noteligible.

9. Concomitant anticoagulation with coumarin agents (e.g., warfarin), direct thrombininhibitors (e.g., dabigatran), direct factor Xa inhibitor betrixaban, or plateletinhibitors (e.g., clopidogrel). Allowed anticoagulants are the following:

10. Prophylactic use of low-dose aspirin for cardio-protection (per localapplicable guidelines) and low-dose low molecular weight heparins (LMWH).

11. Therapeutic doses of LMWH or anticoagulation with direct factor Xa inhibitorsrivaroxaban, edoxaban, or apixaban in subjects without known brain metastaseswho are on a stable dose of the anticoagulant for at least 1 week before firstdose of study treatment without clinically significant hemorrhagiccomplications from the anticoagulation regimen or the tumor.

12. Prothrombin time (PT/INR) or partial thromboplastin time (PTT) test ≥ 1.3 X thelaboratory ULN within 7 days before the first dose of study treatment.

13. The subject 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 AssociationClass 3 or 4, unstable angina pectoris, serious cardiac arrhythmias. ii. Uncontrolled hypertension defined as sustained blood pressure (BP) > 140 mm Hgsystolic 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 of study treatment.

14. Subjects with a diagnosis of incidental, subsegmental PE or DVT within 6 monthsare allowed if stable, asymptomatic, and treated with a stable dose ofpermitted anticoagulation (see exclusion criterion #6) for at least 1 weekbefore first dose of study treatment.

15. Gastrointestinal disorders: i. The subject has evidence of tumor invading the GI tract, active peptic ulcerdisease, inflammatory bowel disease (e.g., Crohn's disease), diverticulitis,cholecystitis, symptomatic cholangitis or appendicitis, acute pancreatitis, acuteobstruction of the pancreatic duct or common bile duct, or gastric outletobstruction. ii. Abdominal fistula, GI perforation, bowel obstruction, or intra-abdominal abscesswithin 6 months before first dose of study treatment. iii. Note: Complete healing of an intra-abdominal abscess must be confirmed beforefirst dose of study treatment.

16. Clinically significant hematuria, hematemesis, or hemoptysis of > 0.5 teaspoon (2.5ml) of red blood, or other history of significant bleeding (e.g., pulmonaryhemorrhage) within 12 weeks before first dose of study treatment.

17. Cavitating pulmonary lesion(s) or known endotracheal or endobronchial diseasemanifestation.

18. Lesions invading or encasing any major blood vessels.

19. Other clinically significant disorders that would preclude safe study participation.

20. Serious non-healing wound/ulcer/bone fracture.

21. Uncompensated/symptomatic hypothyroidism.

22. Moderate to severe hepatic impairment (Child-Pugh B or C).

23. Major surgery (e.g., laparoscopic nephrectomy, GI surgery, removal or biopsy ofbrain metastasis) within 2 weeks before first dose of study treatment. Minorsurgeries within 10 days before first dose of study treatment. Subjects must havecomplete wound healing from major surgery or minor surgery before first dose ofstudy treatment. Subjects with clinically relevant ongoing complications from priorsurgery are not eligible.

24. Corrected QT interval calculated by the Fridericia formula (QTcF) > 500 ms perelectrocardiogram (ECG) within 14 days before first dose of study treatment [addreference for Fridericia formula]. Note: If a single ECG shows a QTcF with an absolute value > 500 ms, two additionalECGs at intervals of approximately 3 min must be performed within 30 min after theinitial ECG, and the average of these three consecutive results for QTcF will beused to determine eligibility.

25. Pregnant or lactating females.

26. Inability to swallow tablets.

27. Previously identified allergy or hypersensitivity to components of the studytreatment formulations.

28. Any other active malignancy at time of first dose of study treatment or diagnosis ofanother malignancy within 3 years prior to first dose of study treatment thatrequires active treatment, except for locally curable cancers that have beenapparently cured, such as basal or squamous cell skin cancer, superficial bladdercancer, or carcinoma in situ of the prostate, cervix, or breast.

29. Any other conditions considered as unacceptable risk by the treating physician.