Trial of Nivolumab in Combination With Ipilimumab in Subjects With Previously Untreated Metastatic Uveal Melanoma (GEM1402)

This is an interventional treatment trial for Uveal Melanoma focused on measuring melanoma Read More

Inclusion Criteria:

1. Written informed consent must be provided;
2. Patients must have a histological diagnosis of uveal melanoma;
3. Progressive metastatic disease at baseline. Progressive disease is defined as new or progressive lesions on cross-sectional imaging;
4. Age>18 years;
5. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 to 1;
6. Measurable disease by CT or MRI per RECIST 1.1 criteria;

Exclusion Criteria:

1. Prior systemic treatment for metastatic uveal melanoma.
2. Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of cervix or breast, or incidental prostate cancer.
3. Autoimmune disease: Patients with a history of inflammatory bowel disease, including ulcerative colitis and Crohn's Disease, are excluded from this study, as are patients with a history of symptomatic disease (eg, rheumatoid arthritis, systemic progressive sclerosis [scleroderma], systemic lupus erythematosus, autoimmune vasculitis [eg, Wegener's Granulomatosis]); motor neuropathy considered of autoimmune origin (e.g. Guillain-Barre Syndrome and Myasthenia Gravis). Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
4. Any underlying medical or psychiatric condition, which in the opinion of the investigator will make the administration of nivolumab and ipilimumab hazardous or obscure the interpretation of Advers Events (AEs), such as a condition associated with frequent diarrhea.
5. Any non-oncology vaccine therapy used for prevention of infectious diseases (for up to 1 month before or after any dose of nivolumab and ipilimumab).
6. A history of prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA4 antibody, or any other antibody or drug specifically targeting T-cell costimulation or immune checkpoint pathways.
7. Concomitant therapy with any of the following: Interleukin (IL) -2, interferon, or other non-study immunotherapy regimens; cytotoxic chemotherapy; immunosuppressive agents; other investigation therapies; or chronic use of systemic corticosteroids, defined as >10mg daily prednisone equivalents. Inhaled or topical steroids, and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
8. Active brain metastases or leptomeningeal metastases. Subjects with brain metastases are eligible if these have been treated and there is no magnetic resonance imaging (MRI) evidence of progression for at least 8 weeks after treatment is complete and within 28 days prior to first dose of study drug administration. There must also be no requirement for immunosuppressive doses of systemic corticosteroids (> 10 mg/day prednisone equivalents) for at least 2 weeks prior to study drug administration.

9. Women of childbearing potential (WOCBP) as defined below, who:

   • are unwilling or unable to use an acceptable method of contraception to avoid pregnancy for their entire study period and for at least 8 weeks after cessation of study drug, or
   • have a positive pregnancy test at baseline, or
   • are pregnant or breastfeeding.