A Phase Ib/II Trial of Interleukin-2 in Combination with Pembrolizumab for Patients with Unresectable or Metastatic Melanoma

Inclusion Criteria
Histologic or cytologic diagnosis of cutaneous melanoma, mucosal melanoma, or melanoma of unknown primary that is considered unresectable (Stage III) or metastatic (Stage IV).
Have measurable disease
Patients must have a brain MRI or CT (with and without contrast) that is free of
active metastases
Normal cardiac function
Normal lung function
Demonstrate adequate organ function
Female subject of childbearing potential should 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.
Female subjects of childbearing potential must 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.
Subject meets institutional requirements for IL-2 therapy
Exclusion Criteria
Has primary ocular melanoma.
Is 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 immunodeficiency or is receiving systemic immunosuppressive steroid therapy or any other form of systemic immunosuppressive therapy within 7 days prior to the first dose of trial treatment. Exception: Physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency is not considered systemic immunosuppressive steroid therapy.
Has received previous high dose IL-2 therapy
Has a history of significant congestive heart failure or significant pulmonary disease
Has a known history of active TB (Bacillus Tuberculosis)
Hypersensitivity to pembrolizumab or any of its excipients, or a known history of hypersensitivity to IL-2 or any component of the formulation
Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study
Day 1 or who has not recovered 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 from adverse events due to a previously administered agent.
Has a 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.
Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
Has a history of inflammatory bowel disease.
Has active autoimmune disease that has required systemic treatment in the 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.
Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis
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., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
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.