Agnostic Therapy in Rare Solid Tumors

Inclusion criteria

• Age 18 years or older.
• Patients with immunohistochemistry for PD-L1 with a combined positive score (CPS) of 10 or higher.
• Patients with progression or intolerance to already approved and accessible treatments for the specific neoplasm and population.
• Documented disease progression radiologically after the last routine treatment.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Measurable lesion per RECIST v1.1. Lesions previously treated with radiotherapy can only be used as target lesions if they are confirmed to be progressing by imaging before enrollment.
• Male participants must meet at least one of the following conditions:
• Considered infertile;
• No fertile partner;
• Has a fertile partner who agrees to follow contraceptive guidance throughout the study period and for at least 6 months after the last dose of Nivolumab;
• and
• Agrees to abstain from sperm donation throughout the study period and for at least 6 months after the last dose of Nivolumab.
• Female participants must meet at least one of the following conditions:
• Considered infertile;
• Agrees to follow contraceptive guidance throughout the study period and for at least 6 months after the last dose of Nivolumab;
• Estimated life expectancy greater than 12 weeks, as determined by the investigator or delegated sub-investigator.
• Preserved organ functions defined by:
• Absolute neutrophil count ≥ 1,000;
• Hemoglobin ≥ 8.0 g/dL (patients may receive transfusions to reach this level);
• Platelet count ≥ 100,000;
• Total bilirubin ≤ 1.5 × Upper Limit of Normal (ULN), or ≤ 3.0 × ULN for patients with Gilbert's syndrome;
• Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) ≤ 2.5 × ULN (≤ 5 × ULN in the presence of liver metastases);
• Creatinine clearance \> 30 mL/min (estimated by Cockcroft-Gault).
• Diagnosis of rare cancer (List I) confirmed by histopathological examination, with the possibility of including other types of rare tumors (incidence of less than 6 in every 100,000) after careful evaluation and approval by the study board.
• List I:
• Urachal adenocarcinoma
• Parathyroid carcinoma
• Nasopharyngeal epithelial tumors
• Fibrolamellar carcinoma of any primary site
• Angiosarcoma of any primary site
• Secretory breast carcinoma
• Anal cancer
• Metaplastic breast carcinoma
• Chromophobe renal carcinoma, Microphthalmia-associated Transcription Factor (MiT) family translocation renal carcinoma; renal carcinoma with Fumarate Hydratase (FH) or Succinate Dehydrogenase (SDH) deficiency
• Carcinosarcoma of any primary site
• Small intestine cancer
• Cholangiocarcinoma
• Sertoli-Leydig cell tumors
• Cervical cancer of non-epidermoid histology
• Tracheal epithelial tumors
• Non-cystadenoma salivary gland tumors
• Mesothelioma of any site
• Neuroblastoma
• Adrenal cancer
• Penile cancer
• Apocrine carcinoma
• Fibrosarcoma of any primary site
• Cancer of unknown primary site
• Hemangioblastoma of any primary site
• Thyroid cancer
• Hepatoblastoma
• Fallopian tube cancer
• Leiomyosarcoma of any primary site
• Vaginal cancer
• Neurofibrosarcoma of any primary site
• Gallbladder cancer
• Osteosarcoma of any primary site
• Bile duct cancer
• Clear cell endometrial carcinoma
• Yolk sac tumor of any primary site
• Non-epidermoid bladder cancer
• Vulvar cancer
• Kaposi's sarcoma
• Epithelial ovarian cancer
• Soft tissue sarcoma
• Urethral cancer
• Granulosa cell tumor of any primary site
• Cystadenoma carcinoma
• Primitive neuroectodermal tumor of any primary site
• Pure or mixed neuroendocrine tumors with neuroendocrine component
• Trophoblastic tumor

Exclusion criteria

• Previous treatment lines with immunotherapy (immune checkpoint inhibitors).
• Pregnant or breastfeeding individuals.
• Limiting comorbidity, in the opinion of the investigator.
• Active infection.
• Major surgery within the last 4 weeks.
• Functional class II or greater heart failure.
• Myocardial infarction or stroke within the last 6 months.
• History of pulmonary fibrosis or pneumonitis.
• Autoimmune diseases, except for patients with vitiligo and/or controlled thyroid/hypothyroidism without the use of immunosuppressors.
• Second invasive primary tumor diagnosed in the last 3 years and/or with active disease, except for localized skin tumors (non-melanoma) that have been treated with curative intent.
• Patients with prolonged QT interval.
• Uncontrolled Central Nervous System (CNS) metastases. Patients who have previously received local treatment, such as radiotherapy, will be eligible if clinical and radiological stability is demonstrated in the 2 weeks prior to the start of treatment. Patients must not be using corticosteroids for managing CNS disease.
• Presence of meningeal carcinomatosis.
• Worsening renal and liver function in the 14 days prior to enrollment.
• History of solid organ transplantation with or without immunosuppression.
• Patients with untreated acquired immunodeficiency. Immunocompromised patients may be included as long as they do not have active opportunistic disease and/or active infection, after thorough clinical evaluation by the investigator or sub-investigator. HIV-positive patients must have documented undetectable viral load prior to inclusion.
• Chronic use of corticosteroids at doses greater than 10 mg/day of prednisone or equivalent. Patients with adrenal insufficiency of non-autoimmune etiology (e.g., previous bilateral adrenalectomy) may be included if they are clinically compensated with 10 mg/day of prednisone or equivalent or less.