Optimization of Immunotherapy Treatment for Advanced Melanoma in the Context of the Public Brazilian Health System (OTIMAS)

Prior treatment

• Uncontrolled Central Nervous System (CNS) metastases: active symptomatic disease in the central nervous system, requiring doses of corticosteroids greater than the equivalent of 10 mg/day of prednisone. Patients previously submitted to local treatment, such as radiotherapy, will be eligible if they have demonstrated clinical stability in the 2 weeks prior to the start of treatment;
• More than one line of prior systemic therapy in the context of metastatic or advanced disease or prior use of polychemotherapy;
• Prior use of anti-PD-1 in the (neo)adjuvant setting;
• Concomitant active malignant neoplasia;
• Use of corticosteroids in a dose equivalent to greater than 10 mg/d of prednisone on a continuous basis.

Other illness

• Leptomeningeal disease
• Uncontrolled associated disease;
• Known active hepatitis B and C;
• HIV with detectable viral load or CD4\<350;
• Active autoimmune disease with use of immunosuppressive therapy or history of autoimmune disease whose risk of recurrence is considered high by the investigator;
• History of malignant neoplasia in the last 5 years, with the exception of squamous cell carcinoma, basal cell carcinoma of the skin, in situ tumors, prostate adenocarcinoma gleason \<=6;
• Infection with systemic involvement in the last 2 weeks;
• History of solid organ transplantation under immunosuppression.

Age

• Pregnancy; effective contraceptive methods should be recommended to women of childbearing age;

Other

• Diagnosis of uveal or mucosal melanoma;
• Diagnosis of acral melanoma;

• Patients with malignant melanoma (with confirmed histopathological diagnosis) stages III and IV not amenable to locoregional treatment or curative treatment
• Measurable disease by RECIST 1.1
• Eastern Cooperative Oncology Group (ECOG) 0, 1 or 2
• Up to 1 (one) line of prior treatment with palliative chemotherapy (monotherapy), with documented progression and no residual toxicities greater than grade 1 according to CTCAE
• Estimated life expectancy greater than 12 weeks
• Adequate renal function, defined as creatinine clearance estimated by the Cockcroft-Gault equation equal to or greater than 30 mL/min;
• Adequate liver function, defined as alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels equal to or less than 2.0 times the upper limit of normal and total bilirubin less than 2 times the upper limit of normal;
• Hemoglobin greater than or equal to 8 g/dL; neutrophil count equal to or greater than 1,000/mm3; platelet count equal to or greater than 100,000/mm3;
• Ability to understand and adhere to study procedures;
• Age over 18 years;
• Absence of active treatment for the underlying disease, with the exception of the use of bisphosphonates;