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

Status: Active


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. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of tumor cells to grow and spread. Giving aldesleukin and pembrolizumab may work better in treating patients with kidney cancer.

Eligibility Criteria

Inclusion Criteria

  • 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
  • Have measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
  • Available tissue from an archival tissue sample or newly obtained core or excisional biopsy of a tumor lesion
  • 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 (patients >= 40 years old)
  • 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 3 and >= 40 years old)
  • 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

  • (Dose levels 1 and 2) - may have received one or more systemic treatments or regimens for metastatic RCC; (dose level 3) - cannot have received prior systemic treatment for RCC
  • Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways)
  • Has received prior therapy with IL-2 or other investigational systemic cytokine therapy signaling through a common gamma-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 or who has not recovered (i.e., =< grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier
  • Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study day 1 or who has not recovered (i.e., =< grade 1 or at baseline) from adverse events due to a previously administered agent * Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
  • 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

Locations & Contacts


Fred Hutch / University of Washington Cancer Consortium
Status: Active
Contact: Scott S. Tykodi
Phone: 206-288-7763

Trial Objectives and Outline


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) weekly on days 1-5 of courses 1 and 2 or aldesleukin IV on days 2-6 of courses 1 and 2. Treatment repeats every 3 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for every 3 months for up to 1 year.

Trial Phase & Type

Trial Phase

Phase I

Trial Type


Lead Organization

Lead Organization
Fred Hutch / University of Washington Cancer Consortium

Principal Investigator
Scott S. Tykodi

Trial IDs

Primary ID 9611
Secondary IDs NCI-2017-01416, RG1717068 ID NCT03260504