Nivolumab, BMS-936558 in Combination With Relatlimab, BMS-986016 in Patients With Metastatic Melanoma Naïve to Prior Immunotherapy in the Metastatic Setting

This study will evaluate the antitumor activity of anti-LAG3 monoclonal antibody relatlimab
and the anti-PD1 monoclonal antibody nivolumab in combination in subjects with unresectable
or metastatic melanoma who have not received prior treatment with immunotherapy. The trial is
designed with a lead-in phase of 2 cycles (4 week) treatment of either nivolumab, relatlimab,
or the combination of nivolumab/relatlimab, followed by a combination phase of
nivolumab/relatlimab treatment in all subjects. This lead-in design with accompanying tumor
biopsies and peripheral blood analyses will enable mechanistic analyses of the effect of LAG3
and PD1 blockade alone and in combination to enhance understanding of mechanisms of response
and resistance. Duration of response, progression free survival, and safety will be assessed
as secondary objectives.

Inclusion Criteria:

• Men or women 18 years of age or older meeting AJCC 8th edition criteria for unresectable
stage IIIB, stage IIIC, stage IIID, or stage IV melanoma who have not received treatment
with immunotherapy in the metastatic setting

Exclusion Criteria:

- Known or suspected CNS metastases, with the following exceptions:

- Subjects with controlled brain metastases will be allowed to enroll. Controlled
brain metastases are defined as no radiographic progression for at least 4 weeks
following radiation and/or surgical treatment at the time of consent. Subjects
must be off steroids for at least 2 weeks prior to randomization.

- Subjects with signs or symptoms of brain metastases are not eligible unless brain
metastases are ruled out by computed tomography or magnetic resonance imaging.

- Active autoimmune disease requiring treatment, with the exception of type 1 diabetes
mellitus, vitiligo, resolved childhood asthma/atopy, controlled hyper/hypothyroidism,
hypoadrenalism or hypopituitarism.

- Prior systemic treatment in the metastatic setting, including anti-PD1, anti-PDL1,
anti-PDL2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting
T-cell costimulation or immune checkpoint pathways; or chemotherapy.

- Prior adjuvant treatment with anti-PD1, anti-PDL1, and/or anti-LAG3 antibody. Note
that prior adjuvant treatment with targeted therapy (e.g. BRAF/MEK inhibition),
anti-CTLA4, or treatment not otherwise specified above would be permitted.

- Ocular melanoma