Aldesleukin and Pembrolizumab in Treating Patients With Advanced or Metastatic Kidney Cancer

  • End date
    Dec 17, 2023
  • participants needed
  • sponsor
    University of Washington
Updated on 28 January 2021
ejection fraction
monoclonal antibodies
metastatic disease
serum pregnancy test
measurable disease
direct bilirubin
glomerular filtration rate
serum bilirubin
serum total bilirubin level
neutrophil count
liver metastasis
pet scan
tumor cells
monoclonal antibody therapy
programmed cell death 1 ligand 1
solid tumour
curative surgery
kidney cancer
metastatic renal cell carcinoma


This phase I trial studies the side effects and best dose of aldesleukin when given together with pembrolizumab in treating patients with kidney cancer that has spread to other parts of the body. Aldesleukin may stimulate white blood cells to kill kidney cancer cells. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to avoid recognition by immune cells. Giving aldesleukin and pembrolizumab may work better in treating patients with kidney cancer.



I. To evaluate the safety and tolerability of aldesleukin (IL-2) combined with pembrolizumab (MK-3475) in patients with metastatic clear cell renal cell carcinoma (RCC).


I. To assess preliminary antitumor activity of pembrolizumab in combination with IL-2.


I. To investigate the association of PD-L1 protein expression by pretreatment tumor with response to treatment.

II. To investigate the association of regulatory T cell (Treg) frequency and Treg to effector T cell (Teff) ratios in peripheral blood and tumor tissue with response to therapy.

III. To investigate the association of de novo serological and cellular responses against the ubiquitous RCC tumor antigen 5T4 with response to therapy.

IV. To investigate the association of tumor infiltrating lymphocyte (TIL) repertoire clonality with response to therapy and to assess the detection of dominant TIL clones within peripheral blood over time in responding patients.

V. To investigate the association of whole genome copy number alterations measured on pretreatment archived, formalin fixed, paraffin embedded (FFPE) tumor with response to therapy.

OUTLINE: This is a dose-escalation study of aldesleukin.

Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Patients also receive aldesleukin subcutaneously (SC) 5 days per week for 6 weeks; or aldesleukin IV on days 2-6 of pembrolizumab cycles 1 and 2. Pembrolizumab treatment repeats every 3 weeks for 4 cycles per treatment course in the absence of clinical disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up via surveillance scans for every 3 months for up to 1 year or until disease progression.

Condition Adenocarcinoma, Malignant neoplasm of kidney, Renal Cell Carcinoma, Stage IV Renal Cell Cancer, Stage III Renal Cell Cancer, Kidney Cancer, Malignant Adenoma, Renal Cell Cancer, Renal Cancer, clear cell renal cell carcinoma, stage iv kidney cancer
Treatment aldesleukin, Pembrolizumab
Clinical Study IdentifierNCT03260504
SponsorUniversity of Washington
Last Modified on28 January 2021


Yes No Not Sure

Inclusion Criteria

Is your age greater than or equal to 18 yrs?
Gender: Male or Female
Do you have any of these conditions: Renal Cell Cancer or Kidney Cancer or Malignant neoplasm of kidney or Malignant Adenoma or Stage IV Renal Cell Cancer or Renal Cancer or Adenocarcinom...?
Do you have any of these conditions: stage iv kidney cancer or Malignant Adenoma or Stage III Renal Cell Cancer or Adenocarcinoma or clear cell renal cell carcinoma or Malignant neoplasm ...?
Do you have any of these conditions: Malignant neoplasm of kidney or Renal Cell Cancer or Malignant Adenoma or stage iv kidney cancer or Kidney Cancer or Renal Cell Carcinoma or Adenocarc...?
Do you have any of these conditions: clear cell renal cell carcinoma or Renal Cell Cancer or stage iv kidney cancer or Stage III Renal Cell Cancer or Renal Cell Carcinoma or Malignant neo...?
Be willing and able to provide written informed consent for the trial
Have histologic confirmation of RCC with a clear cell component
Have advanced (not amenable to potentially curative surgery) or metastatic RCC
Available tissue from an archival tissue sample or newly obtained core or excisional biopsy of a tumor lesion
May have received previous systemic treatments or regimens for metastatic RCC. Prior therapy can include checkpoint blocking antibodies targeting PD-1, PD-L1, or cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) and/or targeted agents including TKIs, mTOR inhibitors, or bevacizumab. Patients may choose to receive study treatment as their initial therapy
Previously treated patients must have documented disease progression after their last line of therapy
Have measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale
Absolute neutrophil count (ANC) >= 1,500 /mcL (within 14 days of treatment initiation)
Platelets >= 100,000/mcL (within 14 days of treatment initiation)
Hemoglobin >= 9 g/dL or >= 5.6 mmol/L (within 14 days of treatment initiation)
Serum creatinine =< 1.5 X upper limit of normal (ULN) OR measured or calculated creatinine clearance (glomerular filtration rate [GFR] can also be used in place of creatinine or CrCl) >= 40 mL/min for subject with creatinine levels > 1.5 X institutional ULN; creatinine clearance should be calculated by Cockcroft-Gault (within 14 days of treatment initiation)
Serum total bilirubin =< 1.5 X ULN OR direct bilirubin =< ULN for subjects with total bilirubin levels > 1.5 ULN (within 14 days of treatment initiation)
Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =< 2.5 X ULN OR =< 5 X ULN for subjects with liver metastases (within 14 days of treatment initiation)
International normalized ratio (INR) or prothrombin time (PT) =< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants (within 14 days of treatment initiation)
Activated partial thromboplastin time (aPTT) =< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants (within 14 days of treatment initiation)
Forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) >= 65% of predicted (dose level 2 and 3)
Left ventricular ejection fraction (LVEF) >= 50% measured by multigated acquisition (MUGA) scan, echo, or stress test study with myocardial perfusion imaging
Normal/negative cardiac stress testing with myocardial perfusion imaging OR cardiac catheterization with non-significant angiogram findings reviewed by a cardiology consultant (dose level 2 and 3)
Female subject of childbearing potential should have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication; if the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication; subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year
Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy

Exclusion Criteria

Has received prior therapy with IL-2 or other investigational systemic cytokine therapy signaling through a common -chain cytokine receptor including IL-7, IL-15 or IL-21
Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of treatment
Has had a prior monoclonal antibody within 4 weeks prior to study day 1. Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study day 1
Adverse events due to prior treatment must be resolved to < grade 1
Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
For patients previously treated with checkpoint blocking antibodies, no history of myocarditis, pneumonitis or nephritis of any grade associated with the prior treatment
Has had autoimmune toxicity associated with prior checkpoint blocking antibodies requiring more than one drug class of immune suppressive therapy to resolve (e.g. steroid-refractory toxicity requiring infliximab, mycophenolate mofetil, tacrolimus or other immune suppressive agent) or requiring continuous immune suppression > 12 weeks, or having a severity judged to be life threatening by the investigator
Has a known additional malignancy that is progressing or requires active treatment; exceptions include locally curable cancers such as basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, or carcinoma in situ of the cervix or breast that has undergone potentially curative therapy
Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
(Dose level 1) subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment
(Dose Level 2 and 3) subjects may not have any history of or current CNS metastases; baseline imaging of the brain is required within 28 days prior to the start of study treatments
Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment
Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents; subjects with vitiligo or resolved childhood asthma/atopy would be an exception to this rule; subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study; subjects with hypothyroidism stable on hormone replacement or Sjorgen's syndrome will not be excluded from the study
Has history of (non-infectious) pneumonitis that required steroids or active, non-infectious pneumonitis
Ongoing symptomatic cardiac dysrhythmias, uncontrolled atrial fibrillation, or prolongation of the corrected QT interval defined as > 450 msec for males and > 470 msec for female
History of any of the following cardiovascular conditions within 6 months of enrollment: cardiac angioplasty or stenting, myocardial infarction, unstable angina, coronary artery bypass graft surgery, class III or IV congestive heart failure as defined by the New York Heart Association, symptomatic peripheral vascular disease, cerebrovascular accident, or transient ischemic attack
Has an active infection requiring systemic therapy
Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment
Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)
Has known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected)
Has received a live vaccine within 30 days prior to the first dose of trial treatment; Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist) are live attenuated vaccines, and are not allowed
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