Combining PD-1 Blockade, CD137 Agonism and Adoptive Cell Therapy for Metastatic Melanoma

Exclusion Criteria

• •Patients with active systemic infections requiring intravenous antibiotics, coagulation disorders, or other major medical illness of the cardiovascular, respiratory or immune system, which in the opinion of the PI or treating co-investigator is not acceptable risk for ACT, are excluded.
• •Patients who have received prior immunotherapy whose side effects have resulted in a requirement of immunosuppressive medications (\>10 mg of prednisone daily or equivalent daily steroid daily, or infliximab, cyclosporine or equivalent immunosuppressive medication) or who have other autoimmune conditions that require immunosuppressive medications as above at the time of screening are excluded.
• •Patients who test positive for Human Immunodeficiency Virus (HIV), Hepatitis B surface antigen, Hepatitis B core antibody, Hepatitis C antibody, Human T-lymphotropic Virus (HTLV) I or II antibody, or are both Rapid plasma reagin (RPR) and Fluorescent treponemal antibody (FTA) positive are excluded.
• •Patients who are pregnant or nursing are excluded.
• •Patients with a significant psychiatric disease, who in the opinion of the principal investigator or his designee, would prevent adequate informed consent or render immunotherapy unsafe will be excluded.
• •Patients with \> 3 untreated CNS metastases or evidence of peri-tumoral edema will be excluded, or patients with CNS metastases of any status who are taking prednisone \>10 mg or equivalent steroid daily will be excluded.
• •Patients with ≤ 3 untreated CNS metastases but with at least one lesion \>1 cm or peri-tumoral edema will be excluded, or patients with CNS metastases of any status who are taking prednisone \>10 mg or equivalent steroid daily will be excluded.
• •Patients with invasive malignancy other than melanoma at the time of enrollment and within 2 years of screening are excluded, except for: adequately treated (i.e. with curative intent) basal or squamous cell carcinoma, in situ carcinoma of the cervix, in situ ductal adenocarcinoma of the breast, in situ prostate cancer, or limited stage bladder cancer or other any other cancers from which the patient has been disease-free for at least 2 years.
• •Patients with treated CNS metastases \> 1 cm or \> 3 in number will be excluded if there is evidence of progressive CNS disease on brain imaging at least 90 days after treatment with surgery and/or radiation therapy, or patients with CNS metastases of any status who are taking prednisone \>10 mg or equivalent will be excluded.
• •Male patients with female partners of childbearing potential who do not agree to use two FDA-accepted forms of contraception during sexual intercourse with women of child-bearing potential from the start of PD-1 antibody therapy and up to at least 31 weeks from the last dose of nivolumab are excluded.
• •Females of childbearing potential who do not agree to use 2 FDA forms of contraception according to study guidelines
• •Prior systemic therapy with a PD-1 blocking antibody
• •Patients who are greater than age 50, or who have a history of coronary artery disease, will be required to undergo cardiac stress testing within 6 months of screening and will be excluded if there is evidence of reversible ischemia.
• •Patients who have a significant history of pulmonary disease that necessitates the use of supplemental oxygen, is associated with dyspnea on walking one block or less, or requires inhaler therapy more than once per week will be required to undergo pulmonary function testing within 6 months of screening and will be excluded if forced expiratory volume 1 (FEV1), forced vital capacity (FVC), or diffusion lung capacity for carbon monoxide (DLCO) is less than 65% of predicted.