High Dose IL-2 and Nivolumab in Treating Patients with Stage III-IV Melanoma or Kidney Cancer
- Patient has the ability to understand and the willingness to sign a written informed 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
- Total bilirubin =< 1.5 x 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.) (within 28 days prior to registration)
- Aspartate aminotransferase (AST) =< 2.5 x ULN or =< 5 x ULN for subjects with known hepatic metastases (within 28 days prior to registration)
- Alanine aminotransferase (ALT) =< 2.5 x ULN or =< 5 x ULN for subjects with known hepatic metastases (within 28 days prior to registration)
- Serum creatinine =< 1.5 mg/dL OR if serum creatinine > 1.5 mg/dL, estimated glomerular filtration rate (GFR) >= 50 mL/min (within 28 days prior to registration)
- Hemoglobin >= 9.0 g/dL (within 28 days prior to registration)
- Absolute neutrophil count (ANC) >= 1000/L without the support of filgrastim (within 28 days prior to registration)
- White blood cells (WBC) >= 3000/L (within 28 days prior to registration)
- Platelet count >= 100 x 10^9/L (within 28 days prior to registration)
- International normalized ratio (INR) < 1.5 x ULN OR for subjects receiving warfarin or low molecular weight heparin (LMWH), the subjects must, in the investigator’s opinion, be clinically stable with no evidence of active bleeding while receiving anticoagulant therapy (within 28 days prior to registration). The INR for these subjects may exceed 1.5 x 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 (condoms)
- Subject’s toxicities from prior treatments must have recovered to a grade 1 or less (except for toxicities such as alopecia or vitiligo)
- Active infection requiring systemic therapy
- Women who are pregnant or breastfeeding
- Second active malignancy within the past 5 years with the exception of localized basal or squamous cell skin cancer, in situ cervical or bladder cancer, or localized prostate cancer under active surveillance
- Active symptomatic central nervous system (CNS) metastases. Prior treated metastases or asymptomatic metastases are allowed. Patient can receive radiation between treatments if deemed medically necessary
- Surgery within 4 weeks prior to study treatment except for minor procedures
- Uncontrolled or poorly-controlled hypertension (> 160 mmHg systolic or > 100 mmHg diastolic for > 4 weeks) despite standard medical management
- Serious or non-healing wounds, ulcers, or bone fractures within 28 days prior to initiation of study treatment
- Any arterial thromboembolic events, including but not limited to myocardial infarction, transient ischemic attack, cerebrovascular accident, or unstable angina, within 6 months prior to initiation of study treatment
- Has any condition that, in the opinion of the investigator, might jeopardize the safety of the patient or interfere with protocol compliance
- Has any mental or medical condition that prevents the patient from giving informed consent or participating in the trial
- Known hypersensitivity to nivolumab or IL-2 or any of their components
- Known history of active tuberculosis
- Concurrent systemic steroid therapy with doses above physiologic level (more than 10 mg of prednisone daily)
- Active autoimmune disease, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with anti-phospholipid syndrome, granulomatosis with polyangiitis, Sjogren’s syndrome, Guillain-Barre syndrome, multiple sclerosis, vasculitis, or glomerulonephritis requiring treatment. Patients cannot be on immunosuppressive medications other than physiologic replacement doses of prednisone (less than 10 mg per day at enrollment) or equivalent steroid. Asymptomatic patients or those stable on non-immunosuppressive medications are eligible
- Treatment with any investigational agent within 21 days prior to initiation of study treatment and the subject must have recovered from the acute toxic effects of the regimen with the exception of prior anti-PD-1
I. To determine the overall response rate (complete response and partial response) for patients receiving anti-PD-1 (nivolumab) and high dose aldesleukin (IL-2) (HD IL-2) in subjects with metastatic melanoma or renal cell carcinoma who have previously progressed on anti-PD-1 therapy.
I. Characterize safety, tolerability and adverse effects (AE) profile of nivolumab with HD IL-2 in subjects with metastatic malignant melanoma or renal cell carcinoma.
II. Measure progression-free survival (PFS) using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 after completion of at least one course of therapy (2 doses of nivolumab, 2 cycles of HD IL-2) for subjects enrolled in the study.
I. Correlate PD-L1 expression and tumor mutational burden (TMB) in archived diagnostic tumor tissue with best clinical response for subjects with metastatic melanoma and renal cell carcinoma.
II. Correlate myeloid-derived suppressor cells and T-cell subsets in peripheral blood during therapy with best clinical response (revised RECIST criteria) and treatment outcome in subjects with stage IV malignant melanoma.
Patients receive nivolumab intravenously (IV) over 30 minutes on days 1 and 35 and aldesleukin IV over 15 minutes every 8 hours on days 8-12 for up to 14 doses and 22-26 for up to 14 doses. Treatment repeats every 35 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3-6 months.
Trial Phase Phase II
Trial Type Treatment
University of California San Diego
- Primary ID 181398
- Secondary IDs NCI-2019-03876, NCT03889782
- Clinicaltrials.gov ID NCT03991130