Clinical Study of Fianlimab in Combination With Cemiplimab Versus Pembrolizumab in Adolescent and Adult Patients With Previously Untreated Unresectable Locally Advanced or Metastatic 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 priorsystemic therapy for advanced unresectable disease

3. Patients who received adjuvant and/or neoadjuvant systemic therapies areeligible if they did not have evidence of progression or recurrence of diseaseand/or discontinued due to occurrence of unmanageable imAEs ≥ grade 3 (with theexclusion of endocrinopathies which are fully controlled by hormonereplacement) while on such therapies. Also, patients must have had atreatment-free and disease-free interval of >6 months. Accrual of thesepatients is limited to approximately 10% of the total population enrolled.

4. Patients with acral and mucosal melanomas are eligible. Accrual will be limitedto 10% of the total population.

5. Measurable disease per RECIST v1.1

6. Previously irradiated lesions can only be counted as target lesions if theyhave been demonstrated to progress and no other target lesion is available

7. Cutaneous lesions should be evaluated as non-target lesions

8. Performance status:

9. For adult patients: Eastern Cooperative Oncology Group (ECOG) performancestatus (PS) 0 or 1

10. For pediatric patients: Karnofsky performance status ≥70 (patients ≥16 years)or Lansky performance status ≥70 (patients ≤16 years)

11. 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 requiredsystemic treatment with immunosuppressive agents. The following arenon-exclusionary: vitiligo, childhood asthma that has resolved, residualhypothyroidism that requires only hormone replacement, psoriasis not requiringsystemic treatment.

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

4. Unknown BRAF V600 mutation status as described in the protocol

5. Systemic immune suppression:

6. Use of immunosuppressive doses of corticosteroids (>10mg of prednisone per dayor equivalent) within 14 days of the first dose of study medication.Physiologic replacement doses are allowed up to and including 10mg ofprednisone/day or equivalent. Inhaled or topical steroids are permitted, ifthey are not for treatment of an autoimmune disorder.

7. Other clinically relevant forms of systemic immune suppression

8. Treatment with other anti-cancer therapy including immuno- therapy, chemotherapy,major surgery or biological therapy within 21 days prior to the first dose of trialtreatment. Adjuvant hormonotherapy used for breast cancer or other hormone-sensitivecancers in long term remission is allowed.

9. History or current evidence of significant (CTCAE Grade ≥2) local or systemicinfection (e. g., cellulitis, pneumonia, septicemia) requiring systemic antibiotictreatment within 14 days prior to the first dose of trial medication.

10. Active or untreated brain metastases or spinal cord compression. Patients withleptomeningeal disease are excluded. Patients with known brain metastases areeligible if they:

11. Received radiotherapy or another appropriate standard therapy for the brainmetastases,

12. Have neurologically returned to baseline (except for residual signs andsymptoms related to the CNS treatment) for at least 14 days prior to enrollment

13. Did not require immunosuppressive doses of corticosteroids therapy (>10mg ofprednisone per day or equivalent) in the 14 days prior to enrollment

14. Are asymptomatic with a single untreated brain metastasis <10 mm in size

15. Participants with a history of myocarditis.

Note: Other protocol-defined Inclusion/ Exclusion criteria apply