| Eligibility |
Inclusion Criteria:
1. Has the ability to understand and willingness to sign a written ICF before the
performance of any study-specific procedures on this protocol and 2022-0515
2. Age = 18 years
3. Has locally advanced or metastatic RCC with predominantly clear cell subtype
4. Has at least one measurable lesion as defined by RECIST version 1.1
5. Has an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-1
6. Has adequate organ function defined as follows:
a. Absolute neutrophil count = 1,500/µL, Hgb level = 9 g/dL and platelet count (Plt)
i. = 100,000/µL without transfusion or growth factor support within 2 weeks prior to
obtaining the hematology values at screening; b. Creatinine clearance = 40
mL/min/1.73m2 c. Transaminase levels (AST/ALT) = 3.0 × upper limit of normal (ULN);
total bilirubin i. (TBILI) = 1.5 mg/dL in the absence of Gilbert's disease
7. Women of child beariring potential must have a negative serum preganancy test within 7
days before first study drug administration
8. Female patients of child bearing potential, or a male patients with a female partner
of child-bearing potential (defined as all women physiologically capable of becoming
pregnant), must agree to use a highly effective method of contraception during
screening, during the period of drug administration and for 120 days after stopping
study drug administration. Highly effective contraception methods include the
following:
1. Total abstinence (defined as refraining from heterosexual intercourse during the
entire period outlined above),
2. Male or female sterilization, or
Use of at least one of the following:
Use of oral, injectable, transdermal, intravaginal, or implantable hormonal methods of
contraception i. Combined estrogen and progestogen containing hormonal contraception
associated with inhibition of ovulation ii. Progestogen-only hormonal contraception
associated with inhibition of ovulation c. Placement of an intrauterine device or
intrauterine system
9. Able to swallow oral medications
10. Able to provide tumor tissue sample (archival or recent acquisition)
11. Patients with brain metastases are eligible providing other measurable disease exists
and brain lesions are controlled for one month (requiring no therapy) and are not life
threatening.
Exclusion Criteria:
1. Has received treatment with any frontline systemic therapy for metastatic RCC
2. Has a history of leptomeningeal disease or spinal cord compression
3. Has a history of autoimmune disease requiring active therapy
4. Has a history of brain metastases except:
1. Patients may be enrolled if they have treated brain metastases with no evidence
of progression or hemorrhage after therapy for brain metastases (e.g. radiation
therapy, surgery, radiosurgery) AND
2. Patients may be enrolled if they do not require ongoing treatment with
dexamethasone or anti-epileptic drugs
5. Has had radiation therapy for bone metastases within 2 weeks, or any other external
radiation therapy (5 days or longer) to sites other than bone, within 4 weeks before
administration of the first dose of study treatment. Patients with clinically relevant
ongoing major complications from prior radiation therapy are not eligible.
6. Has uncontrolled or poorly controlled hypertension, as defined by a sustained blood
pressure (BP) > 140/90 with or without antihypertensive treatment
7. Has had any major cardiovascular event within 6 months prior to study drug
administration including but not limited to myocardial infarction, unstable angina,
cerebrovascular accident, transient ischemic attack, pulmonary embolism, clinically
significant ventricular arrhythmias (e.g. sustained ventricular tachycardia,
ventricular fibrillation, torsades de pointes) or New York Heart Association Class III
or IV heart failure
8. Has any other clinically significant cardiac, respiratory, or other medical or
psychiatric condition that might interfere with participation in the trial or
interfere with the interpretation of trial results, in the opinion of the investigator
or medical monitor
9. Has an active infection requiring systemic treatment
10. Is participating in another therapeutic clinical trial
11. Is receiving chronic concomitant treatment with strong CYP3A4 inducers or CYP3A4
inhibitors
12. Has manifestations of malabsorption due to prior gastrointestinal (GI) surgery or GI
disease
13. Has GI disorders including those associated with a high risk of perforation or fistula
formation:
1. Tumors invading the GI-tract, active peptic ulcer disease, inflammatory bowel
disease, diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis,
acute pancreatitis or acute obstruction of the pancreatic or biliary duct, or
gastric outlet obstruction
2. Abdominal fistula, GI perforation, bowel obstruction, or intra-abdominal abscess
within 6 months before administration of the first dose of study treatment. Note:
complete healing of an intra-abdominal abscess must be confirmed before
administration of the first dose of study treatment
14. Has tumor invading or encasing any major blood vessels
15. Has other clinically significant disorders such as:
1. Serious non-healing wound/ulcer/bone fracture
2. Moderate to severe hepatic impairment (Child-Pugh B or C).
3. Requirement for hemodialysis or peritoneal dialysis
4. History of solid organ transplantation
16. Has had major surgery (e.g., GI surgery, removal or biopsy of brain metastasis) within
2 months before the first study drug administration. Complete wound healing from major
surgery must have occurred 1 month before the first study drug administration and from
minor surgery (e.g., simple excision, tooth extraction) at least 10 days before the
first study drug administration. Patients with clinically relevant ongoing
complications from prior surgery are not eligible
17. Has a prior or concomitant invasive malignancy other than RCC with the exception of
adequately treated basal or squamous cell carcinoma of the skin, cervical carcinoma in
situ or any other malignancy from which the patient has remained disease free for more
than 2 years.
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