A Trial to Learn if Fianlimab and Cemiplimab Are Safe and Work Better Than Anti-PD1 Alone in Adult Participants With Resectable Stage 3 or 4 Melanoma

Key Inclusion Criteria:

1. All patients must be either stage III (IIIB, IIIC, IIID) or stage IV (M1a, M1b, M1c)per American Joint Committee on Cancer (AJCC) 8th edition (Amin 2017) and havehistologically confirmed cutaneous melanoma that is deemed completely surgicallyresectable in order to be eligible as described in the protocol.

2. Patients with stage III melanoma must have clinically detectable disease that isconfirmed as malignant on the pathology report. The pathology report must bereviewed, signed and dated by the investigator; this process will be confirmedduring the interactive voice response system (IVRS) process as described in theprotocol.

3. Patients must be candidates for full resection with curative intent and must be ableto be surgically rendered free of disease with negative margins on resectedspecimens at surgery. The treatment plan including date of surgery must bedocumented by the investigator prior to randomization.

4. All patients must undergo full disease staging through a complete physicalexamination and imaging studies within 4 weeks prior to randomization. Imaging mustinclude a computer tomography (CT) scan of the chest, abdomen, pelvis (if theprimary tumor is on the head/neck then include a CT scan of head/neck), and allknown sites of previously resected disease (if applicable) and brain magneticresonance imaging (MRI) (or brain CT with contrast allowed if MRI iscontraindicated).

5. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1

Key Exclusion Criteria:

Medical conditions:

1. Primary 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. 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, ifgiven to a target lesion, there is pathological evidence of disease progression inthe same lesion.

4. 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 as described in the protocol. Prior/concomitant therapy:

5. Use of immunosuppressive doses of corticosteroids (≥10mg of prednisone per day orequivalent) within 14 days of the first dose of study medication as described in theprotocol.

6. Treatment with any anti-cancer therapy for malignancies other than melanoma,including immuno- therapy, chemotherapy, radiotherapy, or biological therapy in the 5 years prior to randomization as described in the protocol. Other comorbidities:

7. Participants with a history of myocarditis.

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

Note: Other protocol-defined inclusion/ exclusion criteria apply