Phase II Trial of Combination Anti-PD-1 and Aldesleukin for Metastatic Melanoma and Renal Cell Carcinoma

Inclusion criteria

• Participants must have histologically or cytologically confirmed cancer that falls into one of three cohorts: (1) metastatic melanoma or advanced locoregional melanoma not amenable to curative surgical resection and refractory to anti-PD-1 therapy; (2) metastatic renal cell carcinoma (clear cell histology) refractory to at least one line of PD1/PDL1 based therapy; (3) metastatic or advanced locoregional melanoma not amenable to curative surgical resection and naive to anti-PD-1 therapy.
• Participants must have measurable disease (per RECIST v1.1 criteria), metastatic melanoma or renal cell cancer.
• Age \>=18 years of age.
• Clinical performance status of ECOG 0 or 1.
• Willing to practice birth control from the time of enrollment on this study and for four months after treatment.
• Must have a negative pregnancy test because of the potentially dangerous effects of the treatment on the fetus.
• Seronegative for HIV antibody. (The experimental treatment being evaluated in this protocol depends on an intact immune system. Participants who are HIV seropositive may have decreased immune-competence and thus be less responsive to the experimental treatment and more susceptible to its toxicities.)
• Seronegative for hepatitis B antigen and for hepatitis C antibody. If hepatitis C antibody test is positive, then participant must be tested for the presence of antigen by RT-PCR and be HCV RNA negative.
• Participants must have adequate organ and marrow function as defined below:
• ANC \> 1000/mm\^3 without the support of filgrastim
• WBC \>= 3000/mm\^3
• Platelet count \>= 100,000/mm\^3
• Hemoglobin \> 8.0 g/d (Subject may be transfused to reach this cut-off)
• Serum ALT/AST \<= 5.0 x ULN
• Serum creatinine \<= 1.6 mg/dL
• Total bilirubin \<= 2.0 mg/dL, except in participants with Gilbert s Syndrome, who must have a total bilirubin \< 3.0 mg/dL.
• More than four weeks must have elapsed since completion of any prior systemic therapy at the time of enrollment. Note: Participant may have undergone minor surgical procedures or limited field radiotherapy within the four weeks prior to enrollment, as long as related major organ toxicities have recovered to \<= grade 1.
• Ability of subject to understand and the willingness to sign a written informed consent document.
• Willing to sign a Durable Power of Attorney Form.
• Subject must be co-enrolled on protocol 03-C-0277

Exclusion criteria

• Participant is nursing because of the potentially dangerous effects of the treatment on the fetus or infant.
• Concurrent systemic steroid therapy.
• Active systemic infections requiring anti-infective treatment, coagulation disorders, or any other active or uncompensated major medical illnesses.
• Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease and AIDS).
• History of major organ autoimmune disease.
• Grade 3 or 4 major organ irAEs following treatment with anti-PD-1/PD-L1 monotherapy, including but not limited to myocarditis, pneumonitis, colitis, and hepatotoxicity.
• Concurrent opportunistic infections (The experimental treatment being evaluated in this protocol depends on an intact immune system. Participants who have decreased immune-competence may be less responsive to the experimental treatment and more susceptible to its toxicities.)
• History of severe immediate hypersensitivity reaction to pembrolizumab or aldesleukin.
• History of coronary revascularization or ischemic symptoms.
• For select participants with a clinical history prompting cardiac evaluation: last known LVEF \<= 45%.
• For select participants with a clinical history prompting pulmonary evaluation: known FEV1 \<= 50%.
• Participant is receiving any other investigational agents.