A Phase 3 Trial of Fianlimab (Anti-Lag-3) and Cemiplimab versus Pembrolizumab in the Adjuvant Setting in Patients with Completely Resected High-Risk Melanoma.

Key Inclusion Criteria

1. Age ≥12 years on the date of providing informed consent

2. 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 imAEs ≥ 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. Accrual of these patients is limited to

approximately 10% of the total population enrolled in each of the Phase 2 and

Phase 3 parts of the study.

2. Patients with acral and mucosal melanomas are eligible. Combined accrual will be

limited to 10% of the total population enrolled in the Phase 3 part of the study.

3. 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

4. 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)

5. 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 v-Raf murine sarcoma viral oncogene homolog B1 (BRAF) V600 mutation status as

described in the protocol

5. 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

6. 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.

7. 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.

8. Participants with a history of myocarditis.

9. 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