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

NCT ID: NCT05116202

Last Updated: 2025-07-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 110 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-02-02
• Study Completion Date: 2024-05-28

Brief Summary

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.

Conditions

Melanoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

Nivolumab

Intervention Type: DRUG

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

Ipilimumab

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

RO7247669 2100 mg

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

Atezolizumab

Intervention Type: DRUG

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

Tiragolumab

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

RO7247669 2100 mg

Intervention Type: DRUG

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

Tiragolumab

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

RO7247669 2100 mg

Intervention Type: DRUG

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

Tiragolumab

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

RO7247669 600 mg

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

Tiragolumab

Intervention Type: DRUG

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

RO7247669 600 mg

Intervention Type: DRUG

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

Interventions

Nivolumab

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

Intervention Type: DRUG

Ipilimumab

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

Intervention Type: 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.

Intervention Type: DRUG

Atezolizumab

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

Intervention Type: DRUG

Tiragolumab

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

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

Tecentriq, RO5541267; RO7092284

Eligibility Criteria

Inclusion Criteria

• 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.

• 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

• 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

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

City of Hope

Duarte, California, United States

The Angeles Clinic and Research Institute - W LA Office

Los Angeles, California, United States

Moffitt Cancer Center

Tampa, Florida, United States

MD Anderson Cancer Center

Houston, Texas, United States

Melanoma Institute Australia

North Sydney, New South Wales, Australia

Hopital de la Timone

Marseille, , France

APHP - Hospital Saint Louis

Paris, , France

Institut Universitaire du Cancer de Toulouse-Oncopole

Toulouse, , France

Institut Gustave Roussy

Villejuif, , France

Azienda Ospedaliera Universitaria Senese

Siena, Abruzzo, Italy

Istituto Nazionale Tumori Fondazione G. Pascale

Napoli, Campania, Italy

Istituto Europeo Di Oncologia

Milan, Lombardy, Italy

Ospedale S.Maria della Misericordia

Perugia, Umbria, Italy

Hospital Universitario Vall d Hebron

Barcelona, , Spain

Countries

United States; Australia; France; Italy; Spain

References

Long GV, Nair N, Marbach D, Scolyer RA, Wilson S, Cotting D, Staedler N, Amaria RN, Ascierto PA, Tarhini AA, Robert C, Hamid O, Gaudy-Marqueste C, Lebbe C, Munoz-Couselo E, Menzies AM, Pages C, Curigliano G, Mandala M, Jessop N, Bader U, Perdicchio M, Teichgraber V, Muecke M, Markert C, Blank C. Neoadjuvant PD-1 and LAG-3-targeting bispecific antibody and other immune checkpoint inhibitor combinations in resectable melanoma: the randomized phase 1b/2 Morpheus-Melanoma trial. Nat Med. 2025 Sep 24. doi: 10.1038/s41591-025-03967-2. Online ahead of print.

Reference Type: DERIVED

PMID: 40993242 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

BO43328

Identifier Type: -

Identifier Source: org_study_id