Clinical Study of Fianlimab in Combination With Cemiplimab in Adolescent and Adult Patients With Previously Untreated Unresectable Locally Advanced or Metastatic Melanoma

Key Inclusion Criteria:

Age ≥12 years on the date of providing informed consent

Patients with histologically confirmed unresectable Stage III and Stage IV (metastatic) melanoma (AJCC, 8th revised edition) who have not received prior systemic therapy for advanced unresectable disease

1. Patients who received adjuvant and/or neoadjuvant systemic therapies are eligible if they did not have evidence of progression or recurrence of disease and/or discontinued due to occurrence of unmanageable irAEs ≥ grade 3 (with the exclusion of endocrinopathies which are fully controlled by hormone replacement) while on such therapies. Also, patients must have had a treatment-free and disease-free interval of >6 months.
2. Patients with acral and mucosal melanomas are eligible. Accrual will be limited to 10% of the total population.

Measurable disease per RECIST v1.1

1. Previously irradiated lesions can only be counted as target lesions if they have been demonstrated to progress and no other target lesion is available
2. Cutaneous lesions should be evaluated as non-target lesions

Performance status:

1. For adult patients: Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
2. For pediatric patients: Karnofsky performance status ≥70 (patients ≥16 years) or Lansky performance status ≥70 (patients ≤16 years)
3. Anticipated life expectancy of at least 3 months

Key Exclusion Criteria:

1. Uveal melanoma
2. Ongoing or recent (within 2 years) evidence of an 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, psoriasis not requiring systemic treatment.
3. Uncontrolled infection with human immunodeficiency virus (HIV), hepatitis B (HBV) or hepatitis C virus (HCV) infection; or diagnosis of immunodeficiency that is related to, or results in chronic infection
4. Unknown BRAF V600 mutation status as described in the protocol

Systemic immune suppression:

1. Use of immunosuppressive doses of corticosteroids (≤10mg of prednisone per day or equivalent) within 14 days of the first dose of study medication. Physiologic replacement doses are allowed up to and including 10mg of prednisone/day or equivalent. Inhaled or topical steroids are permitted, if they are not for treatment of an autoimmune disorder.
2. Other clinically relevant forms of systemic immune suppression
3. Treatment with other anti-cancer therapy including immuno- therapy, chemotherapy, major surgery or biological therapy within 21 days prior to the first dose of trial treatment. Adjuvant hormonotherapy used for breast cancer or other hormone-sensitive cancers in long term remission is allowed.
4. History or current evidence of significant (CTCAE Grade ≥2) local or systemic infection (e. g., cellulitis, pneumonia, septicemia) requiring systemic antibiotic treatment within 14 days prior to the first dose of trial medication.

Active or untreated brain metastases or spinal cord compression. Patients with leptomeningeal disease are excluded. Patients with known brain metastases are eligible if they:

1. Received radiotherapy or another appropriate standard therapy for the brain metastases,
2. Have neurologically returned to baseline (except for residual signs and symptoms related to the CNS treatment) for at least 14 days prior to enrollment
3. Did not require immunosuppressive doses of corticosteroids therapy (>10mg of prednisone per day or equivalent) in the 14 days prior to enrollment
4. Are asymptomatic with a single untreated brain metastasis <10 mm in size

Note: Other protocol-defined Inclusion/ Exclusion criteria apply