Low-dose Interleukin-2 and Pembrolizumab in Melanoma and Renal Cell Cancer

Main Inclusion Criteria

Stage IV or unresectable stage III malignant melanoma or renal cell carcinoma.

Melanoma

Patients must have failed anti-PD-1/PD-L1 antibody therapy.
Patients must have failed ipilimumab or be intolerant of ipilimumab and therefore unable to receive ipilimumab.
Patients may, but are not obligated, to have failed high- dose IL2.
BRAF status must be known or unable to be performed. If the melanoma expresses a BRAF mutation of V600E, V600K, or V600R patient must have received and progressed through a BRAF inhibitor or have failed that therapy due to toxicity.

Renal Cell Carcinoma

Patients must have failed anti-PD-1/PD-L1 antibody therapy.
Patients must have failed a VEGF pathway inhibitor and a second tyrosine kinase inhibitor.
Patients may, but are not obligated, to have failed high- dose IL2.
Measurable disease based upon RECIST 1.1.
Subjects with brain metastases will be eligible if the following are true:

Subjects with ≤ 3 brain metastases

All metastases are ≤ 3 cm
All metastases have been treated and are asymptomatic
Steroids are not required for management of the brain metastases
All metastases have been stable for 1 month following treatment

Subjects with > 3 brain metastases

All metastases are ≤ 3 cm
All metastases have been treated and are asymptomatic
Steroids are not required for management of the brain metastases
All metastases have been stable for 6 months following treatment
Performance status: ECOG 0-1.
Adequate organ function.
Ability to provide informed consent.

Main Exclusion Criteria:

Pregnancy
Currently participating and 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.
Has a diagnosis of primary or secondary immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 3 weeks prior to the first dose of trial treatment. Replacement doses of steroids are permitted.
Known history of active TB (Bacillus Tuberculosis)
Hypersensitivity to pembrolizumab or any of its excipients.
Known additional malignancies (exceptions DCIS or LCIS, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy).
Prior anti-cancer monoclonal antibody (mAb) within 3 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 3 weeks earlier.
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.
Known carcinomatous meningitis.
Active autoimmune disease that has required systemic treatment in the past 2 years. Patients may be eligible if they have the following autoimmune diseases: thyroiditis or hypothyroidism, mild arthritis, diabetes, resolved hypophysitis, ulcerative colitis after total abdominal colectomy.
Active infection requiring systemic therapy.
Known psychiatric or substance abuse disorders.
Known history of Human Immunodeficiency Virus (HIV).
Known active Hepatitis B virus (HBV) or Hepatitis C virus (HCV).
Has received a live vaccine within 30 days of planned start of study therapy.
Severe chronic pulmonary disease.
Congestive heart failure, angina, or symptomatic cardiac arrhythmia or is classified according to the New York Heart Association classification as having Class III or IV heart disease.
History of (non-infectious) pneumonitis that required steroids or current pneumonitis.