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Patients with a renal mass consistent with a clinical stage >= T3Nx or TanyN+ or deemed unresectable by surgeon |
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Renal cell carcinoma with clear cell component on pre-treatment biopsy of the primary tumor |
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The participant (or legally acceptable representative if applicable) provides written informed consent and the willingness and ability to comply with all aspects of the protocol |
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Have an Eastern Cooperative Oncology Group (ECOG) performance status =< 1 |
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Absolute neutrophil count (ANC) >= 1500/uL (specimens must be collected within 72 hours prior to the start of study treatment) |
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Platelets >= 100 000/uL (specimens must be collected within 72 hours prior to the start of study treatment) |
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Hemoglobin >= 9.0 g/dL (specimens must be collected within 72 hours prior to the start of study treatment) or ≥5.6 mmol/La |
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Renal |
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Creatinine =≤1.5 × ULN OR Measured or calculatedb creatinine clearance (GFR can also be |
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used in place of creatinine or CrCl)=≥30 mL/min for participant with creatinine levels >1.5 |
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× institutional ULN |
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Creatinine clearance (CrCl) calculated per the Cockcroft and Gault formula |
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Hepatic |
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Total bilirubin=≤1.5 ×ULN OR direct bilirubin ≤ULN for participants with total bilirubin |
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levels >1.5 × ULN AST (SGOT) and ALT (SGPT)=≤2.5 × ULN (≤5 × ULN for participants with |
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liver metastases) |
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Coagulation |
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International normalized ratio (INR) OR prothrombin time (PT) Activated partial |
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thromboplastin time (aPTT)=≤1.5 × ULN unless participant is receiving anticoagulant therapy |
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as long as PT or aPTT is within therapeutic range of intended use of anticoagulants |
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ALT (SGPT)=alanine aminotransferase (serum glutamic pyruvic transaminase); AST |
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(SGOT)=aspartate aminotransferase (serum glutamic oxaloacetic transaminase); GFR=glomerular |
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filtration rate; ULN=upper limit of normal |
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Criteria must be met without erythropoietin dependency and without packed red blood |
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cell (pRBC) transfusion within last 2 weeks |
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Creatinine clearance (CrCl) should be calculated per institutional standard |
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International normalized ratio (INR) OR prothrombin time (PT) =< 1.5 x upper |
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limit of normal (ULN) unless participant is receiving anticoagulant therapy as |
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long as PT or activated partial thromboplastin time (aPTT) is within therapeutic |
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range of intended use of anticoagulants (specimens must be collected within 72 |
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hours prior to the start of study treatment) |
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Activated partial thromboplastin time (aPTT) =< 1.5 x ULN unless participant is |
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receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range |
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of intended use of anticoagulants (specimens must be collected within 72 hours |
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prior to the start of study treatment) |
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Serum creatinine =< 1.5 x ULN OR measured or calculated creatinine clearance |
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(glomerular filtration rate [GFR] can also be used in place of creatinine or |
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creatinine clearance [CrCl]) >= 40 mL/min (>= 0.67 mL/sec) for participant with |
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creatinine levels > 1.5 x institutional ULN (specimens must be collected within |
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hours prior to the start of study treatment) |
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Total bilirubin =< 1.5 x ULN OR direct bilirubin =< ULN for participants with |
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total bilirubin levels > 1.5 x ULN (specimens must be collected within 72 hours |
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prior to the start of study treatment) |
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Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3 x ULN |
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(=< 5 x ULN for participants with liver metastases) (specimens must be collected |
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within 72 hours prior to the start of study treatment) |
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All females must have a negative serum or urine pregnancy test (minimum |
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sensitivity 25 IU/L or equivalent units of beta-human chorionic gonadotropin |
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[beta-hCG]) at the screening visit and the baseline visit. A pregnancy test needs |
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to be performed within 72 hours of the first dose of study drug. Women of |
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childbearing potential (WOCBP) must agree to use a highly effective method of |
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contraception for the entire study period and for 120 days after study |
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discontinuation |
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Male subjects who are partners of women of childbearing potential must use a |
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condom and their female partners of childbearing potential must use a highly |
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effective method of contraception beginning at least 1 menstrual cycle prior to |
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starting study drugs, throughout the entire study period, and for 120 days after |
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the last dose of study drug, unless the male subjects are totally sexually |
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abstinent or have undergone a successful vasectomy with confirmed azoospermia or |
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unless the female partners have been sterilized surgically or are otherwise |
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proven sterile |
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Evidence of metastatic disease on pre-treatment imaging
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Cardiovascular disorders
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Serious non-healing wound/ulcer/bone fracture
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Has an active infection requiring systemic therapy
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The subject has received of any type of cytotoxic, biologic or other systemic
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anticancer therapy for kidney cancer
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The subject has received any other type of investigational agent within 28 days before
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the first dose of study treatment
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Excluding the primary tumor leading to enrollment in this study, any other active
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malignancy (except for localized prostate cancer, definitively treated melanoma
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in-situ, basal or squamous cell carcinoma of the skin, or carcinoma in-situ of the
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bladder or cervix) within the past 24 months
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Prior treatment with lenvatinib or any agent directed against PD-1, PD-L1 or PD-L2, or
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another stimulatory or co inhibitory T-cell receptor (e.g. CTLA-4, OX 40, CD137)
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Is pregnant or breastfeeding, or expecting to conceive or father children within the
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projected duration of the study, starting with the screening visit through 120 days
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after the last dose of trial treatment
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Subjects having > 1+ proteinuria on urinalysis will undergo 24-hour urine collection
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for quantitative assessment of proteinuria. Subjects with urine protein >= 1 g/24-hour
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will be ineligible
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Gastrointestinal malabsorption, gastrointestinal anastomosis, or any other condition
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that might affect the absorption of lenvatinib
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The subject has uncontrolled, significant intercurrent or recent illness including
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but not limited to, the following conditions
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New York Heart Association congestive heart failure of grade II or above
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unstable angina, myocardial infarction within the past 6 months, or serious
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cardiac arrhythmia associated with significant cardiovascular impairment
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within the past 6 months
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Uncontrolled hypertension defined as sustained blood pressure (BP) > 150 mm
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Hg systolic or > 90 mm Hg diastolic despite optimal antihypertensive
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treatment
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Prolongation of corrected QT (QTc) interval to > 480 msec per
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electrocardiogram (ECG) within 28 days before first dose of study treatment
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Clinically significant hematemesis, or hemoptysis of > 0.5 teaspoon (2.5 ml) of
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red blood, or other history of significant bleeding (e.g. pulmonary hemorrhage)
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within 3 weeks prior to the first dose of study drug
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History of organ allograft (subject has had an allogenic tissue/solid organ
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transplant)
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Biologic response modifiers (e.g. granulocyte colony-stimulating factor) within 4
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weeks before study entry. Chronic erythropoietin therapy is permitted provided that no
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dose adjustments were made within 2 months before first dose of study treatment
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Subjects must have recovered adequately from any toxicity and/or complications from
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major surgery prior to starting therapy
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Has received a live or live-attenuated vaccine within 30 days prior to the first dose
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of study drug. Examples of live vaccines include, but are not limited to, the
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following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever
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rabies, Bacillus Calmette-Guerin (BCG), and typhoid vaccine. Seasonal influenza
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vaccines for injection are generally killed virus vaccines and are allowed; however
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intranasal influenza vaccines (e.g. FluMist are live attenuated vaccines and are not
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allowed
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Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
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(in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of
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immunosuppressive therapy within 7 days prior to the first dose of study drug
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Has active autoimmune disease that has required systemic treatment in the past 2 years
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(i.e. with use of disease modifying agents, corticosteroids or immunosuppressive
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drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid
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replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a
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form of systemic treatment
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Has a history of (non-infectious) pneumonitis/interstitial lung disease that required
|
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steroids or has current pneumonitis/interstitial lung disease
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Has a known history of active Hepatitis B (e.g., hepatitis B surface antigen [HBsAg])
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or hepatitis C (e.g., HCV RNA qualitative is detected)
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Has uncontrolled HIV defined by a CD4+ count < 350 cells/uL, an AIDS-defining
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opportunistic infection within the last 12 months prior to study enrollment or
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|
documented multidrug resistance that prevents effective HIV therapy
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Has a history or current evidence of any condition, therapy, or laboratory abnormality
|
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|
|
that might confound the results of the study, interfere with the subject's
|
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|
participation for the full duration of the study, or is not in the best interest of
|
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the subject to participate, in the opinion of the treating investigator
|
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