A Study Evaluating the Efficacy and Safety of Multiple Treatment Combinations in Patients With Melanoma (Morpheus-Melanoma)

Inclusion Criteria for Cohort 1:

* ECOG performance status (PS) of 0 or 1
* Histologically confirmed resectable Stage III melanoma according to AJCC-8 and no history of in-transit metastases within the last 6 months
* Fit and planned for CLND
* Measurable disease according to RECIST v1.1
* Availability of a representative tumor specimen
* Adequate hematologic and end-organ function
* For patients receiving therapeutic anticoagulation: stable anticoagulant regimen
* Negative HIV test, negative hepatitis B surface antibody (HBsAb), and negative total hepatitis B core antibody (HBcAb) test, and negative hepatitis C virus (HCV) at screening. Patients with a positive HIV test at screening are eligible provided they are stable on anti-retroviral therapy, have a CD4 count \>= 200/μL, and have an undetectable viral load.

Exclusion Criteria for Cohort 1:

* Mucosal, uveal and acral lentiginous melanoma
* Distantly metastasized melanoma
* History of in-transit metastases within the last 6 months
* Prior radiotherapy
* Prior immunotherapy, including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies, and other systemic therapy for melanoma
* Treatment with investigational therapy within 28 days prior to initiation of study treatment
* Treatment with systemic immunostimulatory agents within 4 weeks or 5 drug-elimination half-lives (whichever is longer) prior to initiation of study treatment
* Prior allogeneic stem cell or solid organ transplantation
* Known immunodeficiency or conditions requiring treatment with systemic immunosuppressive medication, or anticipation of need for systemic immunosuppressant medication during study treatment
* Active or history of autoimmune disease or immune deficiency

Inclusion Criteria for Cohort 2:

* ECOG PS of 0 or 1
* Life expectancy \>= 3 months, as determined by the investigator
* Histologically confirmed Stage IV (metastatic) cutaneous melanoma according to AJCC-8
* Disease progression during or following at least one but no more than two lines of treatment for metastatic disease
* Measurable disease according to RECIST v1.1
* Availability of a representative tumor specimen
* Adequate hematologic and end-organ function
* For patients receiving therapeutic anticoagulation: stable anticoagulant regimen
* Negative HIV test, negative hepatitis B surface antibody (HBsAb), and negative total hepatitis B core antibody (HBcAb) test, and negative hepatitis C virus (HCV) at screening. Patients with a positive HIV test at screening are eligible provided they are stable on anti-retroviral therapy, have a CD4 count \>= 200/μL, and have an undetectable viral load.

Exclusion Criteria for Cohort 2:

* Mucosal and uveal melanoma
* Treatment with investigational therapy within 28 days prior to initiation of study treatment
* Treatment with systemic immunostimulatory agents within 4 weeks or 5 drug-elimination half-lives (whichever is longer) prior to initiation of study treatment
* Prior allogeneic stem cell or solid organ transplantation
* Known immunodeficiency or conditions requiring treatment with systemic immunosuppressive medication, or anticipation of need for systemic immunosuppressant medication during study treatment
* Active or history of autoimmune disease or immune deficiency
* Symptomatic, untreated, or progressing CNS metastases
* Active or history of carcinomatous meningitis/leptomeningeal disease
* Uncontrolled tumor-related pain
* Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures
* Uncontrolled or symptomatic hypercalcemia