High Dose IL-2 in Combination With Anti-PD-1 to Overcome Anti-PD-1 Resistance in Metastatic Melanoma and Renal Cell Carcinoma

Inclusion Criteria

• •Patient has the ability to understand and the willingness to sign a written informed consent.
• •Age ≥ 18 years at the time of consent.
• •At least 6 weeks of prior anti-PD-1 therapy with documented clinical or radiographic progression. Last anti-PD-1 therapy must be within 6 months of enrollment.
• •Histologically-confirmed diagnosis of unresectable stage III or metastatic (stage IV) melanoma or renal cell carcinoma
• •Measurable disease, defined as at least 1 tumor that fulfills the criteria for a target lesion according to RECIST 1.1, and obtained by imaging within 28 days prior registration for protocol therapy.
• •Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 28 days prior to registration for protocol therapy.
• •Adequate hepatic function within 28 days prior to registration for protocol therapy defined as meeting all of the following criteria:
• •total bilirubin ≤ 1.5 × upper limit of normal (ULN) OR direct bilirubin ≤ ULN for subjects with total bilirubin levels \> 1.5 x ULN (except in patients with Gilbert's syndrome who must have a total bilirubin less than 3.0 mg/dl.)
• •* and aspartate aminotransferase (AST) ≤ 2.5 × ULN or ≤ 5 × ULN for subjects with known hepatic metastases
• •* and alanine aminotransferase (ALT) ≤ 2.5 × ULN or ≤ 5 × ULN for subjects with known hepatic metastases
• •Adequate renal function within 28 days prior to registration for protocol therapy defined by either of the following criteria:
• •* Serum creatinine ≤ 1.5 mg/dL
• •* OR if serum creatinine \> 1.5 mg/dL, estimated glomerular filtration rate (GFR) ≥ 50 mL/min
• •Adequate hematologic function within 28 days prior to registration for protocol therapy defined as meeting all of the following criteria:
• •* hemoglobin ≥ 9.0 g/dL
• •* and absolute neutrophil count (ANC) ≥ 1000/L without the support of filgrastim
• •* white blood cells (WBC) ≥ 3000/L
• •* and platelet count ≥ 100 × 109/L
• •Adequate coagulation functioning within 28 days prior to registration for protocol therapy defined by either of the following criteria:
• •* INR \< 1.5 × ULN
• •* OR for subjects receiving warfarin or LMWH, the subjects must, in the investigator's opinion, be clinically stable with no evidence of active bleeding while receiving anticoagulant therapy. The INR for these subjects may exceed 1.5 × ULN if that is the goal of anticoagulant therapy.
• •Adequate pulmonary and cardiac function for HD IL-2 (will be assessed clinically)
• •Female subjects of childbearing potential must have confirmed negative urine or serum pregnancy test prior to drug administration and be willing to use two methods of birth control.
• •Male subjects who are not surgically sterile (vasectomy) must agree to use an adequate method of contraception.
• •Subject's toxicities from prior treatments must have recovered to a grade 1 or less (except for toxicities such as alopecia or vitiligo)