PROSECCO: A Phase 2, Single Arm, Neoadjuvant Study Evaluating Combination Cemiplimab, Fianlimab, And Ipilimumab In Patients With Surgically Resectable Melanoma

14. Primary uveal melanoma

15. Ongoing or recent (within 2 years) of active autoimmune disease that required systemic treatment with immunosuppressive agents. The following are non-exclusionary: vitiligo, childhood asthma that has resolved, residual hypothyroidism that requires only hormone replacement, and psoriasis not requiring systemic treatment.

16. Patients must not have received any prior systemic anti-cancer therapy for melanoma. Prior radiotherapy for melanoma is allowed if not given to a target lesion, or if given to a target lesion there is pathological evidence of disease progression in the same lesion.

17. Uncontrolled infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) infection; or diagnosis of immunodeficiency that is related to, or results in chronic infection.

Notes:

1. Patients with known HIV who have controlled infection (undetectable viral load and CD4 count above 350 either spontaneously or on a stable antiviral regimen) are permitted. For patients with controlled HIV infection, monitoring will be performed per local standards.

2. Patients with known hepatitis B (HepBsAg+) who have controlled infection (serum hepatitis B virus DNA PCR that is below the limit of detection AND receiving anti-viral therapy for hepatitis B) are permitted. Patients with controlled infections must undergo periodic monitoring of HBV DNA per local standards and must remain on anti-viral therapy for at least 6 months beyond the last dose of investigational study drug.

3. Patients who are known hepatitis C virus antibody positive (HCV Ab+) who have controlled infection (undetectable HCV RNA by PCR either spontaneously or in response to a successful prior course of anti-HCV therapy) are permitted.

4. Patients with HIV or hepatitis must be reviewed by a qualified specialist (eg, infectious disease or hepatologist) managing this disease prior to commencing and regularly throughout the duration of their participation in the trial.

18. Concurrent malignancy that is currently progressing or requiring active treatment within the past 2 years except for cancers will a negligible risk of metastasis or death (adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized early-stage prostate cancer or ductal carcinoma in situ of the breast).

19. Use of immunosuppressive dose of corticosteroids (≥ 10mg of prednisone or equivalent) within 14 days of the first dose of study medication. Inhaled or topical steroids are permitted, provided that they are not for treatment of an active autoimmune disorder.

20. Pregnant or breastfeeding women.

21. Received a live vaccine within 30 days of planned start of study medication.

a. Live or live attenuated vaccination with replicating potential. If a patient intends to receive a COVID-19 vaccine before the start of study drug, participation in the study should be delayed at least 1 week after any COVID-19 vaccination. During the treatment period, it is recommended to delay COVID-19 vaccination until patients are receiving and tolerating a steady dose of study drug. A vaccine dose should not be less than 48 hours before or after study drug dosing.

22. Participants with a history of myocarditis.

23. Troponin T (TnT) or troponin I (TnI) \> 2x institutional ULN at baseline.

a. Patients with TnT or TnI levels between \> 1 to 2x ULN are permitted if repeat levels within 24 hours are ≤ 1x ULN. If TnT or TnI levels are \> 1 to 2x ULN within 24 hours, the subject may undergo a cardiac evaluation and be considered for treatment by the investigator based on the medical judgement in the patient's best interest.

24. History or current evidence of significant (NCI-CTCAE grade ≥2) local or systemic infection (e.g., cellulitis, pneumonia, septicemia) requiring systemic antibiotic treatment within 2 weeks prior to the first dose of trial medication.

25. Active infection requiring therapy.

26. Known hypersensitivity to the active substances or to any of the excipients.

27. Presence of a severe concurrent illness or other condition (e.g., psychological, family, sociological, or geographical circumstances) that does not permit adequate follow-up and compliance with the protocol.

28. Prior allogeneic stem cell transplant or solid organ transplant.

29. Any medical condition that in the opinion of the investigator would make participation in the study not in the best interest of the patient.

What this study is about