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.