Clinical Trial Finder

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

Arms

Active Comparator: Cohort 1: Nivolumab + Ipilimumab

Cohort 1 participants in the nivolumab plus ipilimumab arm will receive treatment for 2 cycles (6 weeks) on Day 1 of each cycle (cycle length 21 days) until surgery, or until unacceptable toxicity or loss of clinical benefit, whichever occurs first.

Experimental: Cohort 1: RO7247669 2100 mg

Cohort 1 participants in the RO7247669 arm will receive treatment for 2 cycles (6 weeks) until surgery, or until unacceptable toxicity or loss of clinical benefit, whichever occurs first.

Experimental: Cohort 1: + Atezolizumab + Tiragolumab

Cohort 1 participants in the atezolizumab plus tiragolumab arm will receive treatment for 2 cycles (6 weeks) until surgery, or until unacceptable toxicity or loss of clinical benefit, whichever occurs first.

Experimental: Cohort 1: RO7247669 2100 mg + Tiragolumab

Cohort 1 participants in the RO7247669 plus tiragolumab arm will receive treatment for 2 cycles (6 weeks) until surgery, or until unacceptable toxicity or loss of clinical benefit, whichever occurs first.

Experimental: Cohort 2: RO7247669 2100 mg + Tiragolumab

Cohort 2 participants in RO7247669 plus tiragolumab arm will receive treatment until unacceptable toxicity or loss of clinical benefit as determined by the investigator after an integrated assessment of radiographic and biochemical data, local biopsy results (if available), and clinical status.

Experimental: Cohort 1: RO7247669 600 mg

Cohort 1 participants in the RO7247669 arm will receive treatment for 2 cycles (6 weeks) until surgery, or until unacceptable toxicity or loss of clinical benefit, whichever occurs first.

Experimental: Cohort 1: RO7247669 600 mg + Tiragolumab

Cohort 1 participants in the RO7247669 plus tiragolumab arm will receive treatment for 2 cycles (6 weeks) until surgery, or until unacceptable toxicity or loss of clinical benefit, whichever occurs first.

Interventions

Drug: - Nivolumab

Nivolumab will be administered at a dose of 3 mg/kg IV on Day 1 of each 21 day cycle.

Drug: - Ipilimumab

Ipilimumab will be administered at a dose of 1 mg/kg by IV on Day 1 of each 21 day cycle.

Drug: - RO7247669 2100 mg

RO7247669 will be administered at a dose of 2100 mg by IV infusion on Day 1 of each 21 day cycle.

Drug: - Atezolizumab

Atezolizumab will be administered at a dose of 1200 mg IV on Day 1 of each 21 day cycle.

Drug: - Tiragolumab

Tiragolumab will be administered at a dose of 600 mg IV on Day 1 of each 21 day cycle.

Drug: - RO7247669 600 mg

RO7247669 will be administered at a dose of 600 mg by IV infusion on Day 1 of each 21 day cycle.