Clinical Trial 18536

Cancer Type:
Interventions:IL-2 (Interleukin-2); Pembrolizumab (Keytruda)

Study Type: Treatment
Phase of Study: Phase II

  • Mayer Fishman


Study Title

Coordinated High Dose Interleukin-2 (aldesleukin, Proleukin) and Pembrolizumab (anti-PD1, Keytruda) for Therapy of Metastatic Kidney Cancer


The main purpose of this study is to evaluate the effects of the interleukin-2 given in combination with pembrolizumab. Interleukin-2 (IL-2) is also called aldesleukin, or Proleukin¿. Pembrolizumab is also called Keytruda¿, or anti-PD-1 antibody.


Primary Objective & Hypothesis - Objective: Estimate the frequencies of disease response so as to be a basis to commit to more development of this schedule. Note that this is framed broadly, with the understanding that the decision to commit to further development of the schedule includes a variety of feasibility endpoints. The ORR will be defined as the CR + PR patients, with confirmation of the response status (numerator), among those receiving at least the first IL-2 dose, of cycle B2 (denominator). Hypothesis: H0: ORR is 45%. Thus, a 45% ORR (CR + PR) would be considered of definite interest for further development, contingent on the feasibility assessment as well as part of the decision. This is the hypothesis technically driving the sample size: With N= 21, and the exact binomial one-sided á = .0431 and the power = .8029. (The actual testing will be computed using the actual enrollment, by the study statistician.). Secondary Objectives & Hypotheses - Objective: Feasible improvement of CR rate. Hypothesis: The study is not powered for a definitive assessment, but >15% CR would be of interest. Objective: This is an exploratory safety objective: OS will be not demonstrably inferior to contemporary subjects with matched clinical risk features from PROCLAIM database observed OS (using p > .05). Hypothesis: H0: OS[1-year] is more than 20% lower than matched controls HA: ORR is same or better (using p > .05).

Inclusion Criteria

  • Age 18 years or older
  • Diagnosis/Condition for Entry into the Trial: Metastatic kidney cancer. Clear cell histology component from primary or metastatic lesion.
  • Willing and able to provide written informed consent for the trial.
  • Age over 18 on day of signing informed consent.
  • Have measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
  • Willing to provide tissue from a newly obtained or archival tissue, if available.
  • Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
  • Demonstrate adequate organ function, as outlined in study documentation.
  • Females of childbearing potential must have a negative urine or serum pregnancy 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.
  • Females of childbearing potential must agree 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.
  • Males must 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.
  • Cardiac testing with either exercise stress test or thallium stress test, within 3 months of start of the first treatment day. Atrial fibrillation that is rate controlled is allowed. Note - the first treatment day is about 9 weeks before the first IL-2 treatment day. If a cardiologist's evaluation determines that this is superfluous based on other assessments, then this may be omitted.
  • Pulmonary function test is required, within 3 months of start.

  • Exclusion Criteria

  • Receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
  • Diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
  • Known history of active Bacillus Tuberculosis (TB).
  • Hypersensitivity to pembrolizumab or any of its excipients.
  • The number of prior therapies is restricted: (a) Zero or one prior therapies during the preceding year. (b) No prior PD-1 or PD-L1 antibody therapies. (c) Prior IL-2 is allowed, if it finished more than 1 year prior. (d) Not counted as medical therapies: nephrectomy, radiation therapy, other energy-ablative techniques, or metastasectomy.
  • Prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered > 4 weeks earlier.
  • Prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or has not recovered from adverse events due to a previously administered agent. NOTE: Patients with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study. NOTE: If received major surgery, must have recovered adequately from toxicity and/or complications from the intervention prior to starting therapy.
  • Known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
  • Known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Patients with previously treated brain metastases may participate provided they are stable, have no evidence of new or enlarging brain metastases, and not using steroids for at least 7 days prior to trial treatment. Carcinomatous meningitis is excluded regardless of clinical stability.
  • Active autoimmune disease that has required systemic treatment in past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment that would be exclusionary.
  • Known history of, or any evidence of active, non-infectious pneumonitis.
  • An active infection requiring systemic therapy.
  • History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with participation for the full duration of the trial, or is not in the best interest of the patient to participate.
  • Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  • 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 received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
  • Known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
  • Known active Hepatitis B or Hepatitis C.
  • Has received a live vaccine within 30 days of planned start of study therapy. 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.
  • Myocardial infarction, stroke, coronary artery bypass surgery, coronary stent, or unstable angina within 1 year.