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