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

Roche

Status and phase: Completed; Phase 2; Phase 1

Conditions: Melanoma

Treatments: Drug: Ipilimumab; Drug: RO7247669 600 mg; Drug: Atezolizumab; Drug: Tiragolumab; Drug: RO7247669 2100 mg; Drug: Nivolumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT05116202

BO43328

Details and patient eligibility

About

This study will evaluate the efficacy, safety, and pharmacokinetics of treatment combinations in cancer immunotherapy (CIT)-naive participants with resectable Stage III melanoma (Cohort 1) and in participants with Stage IV melanoma (Cohort 2). The study is designed with the flexibility to open new treatment arms as new treatments become available, close existing treatment arms that demonstrate minimal clinical activity or unacceptable toxicity, and modify the participant population.

Enrollment: 110 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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110 participants in 7 patient groups

Cohort 1: Nivolumab + Ipilimumab

Active Comparator group

Description:

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.

Treatment:

Drug: Nivolumab

Drug: Ipilimumab

Cohort 1: RO7247669 2100 mg

Experimental group

Description:

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.

Treatment:

Drug: RO7247669 2100 mg

Cohort 1: + Atezolizumab + Tiragolumab

Experimental group

Description:

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.

Treatment:

Drug: Tiragolumab

Drug: Atezolizumab

Cohort 1: RO7247669 2100 mg + Tiragolumab

Experimental group

Description:

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.

Treatment:

Drug: RO7247669 2100 mg

Drug: Tiragolumab

Cohort 2: RO7247669 2100 mg + Tiragolumab

Experimental group

Description:

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.

Treatment:

Drug: RO7247669 2100 mg

Drug: Tiragolumab

Cohort 1: RO7247669 600 mg

Experimental group

Description:

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.

Treatment:

Drug: RO7247669 600 mg

Cohort 1: RO7247669 600 mg + Tiragolumab

Experimental group

Description:

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.

Treatment:

Drug: Tiragolumab

Drug: RO7247669 600 mg