A Study Evaluating the Efficacy and Safety of Multiple Treatment Combinations in Patients With Melanoma (Morpheus-Melanoma)
A Phase Ib/II, Open-Label, Multicenter, Randomized Umbrella Study Evaluating the Efficacy and Safety of Multiple Treatment Combinations in Patients With Melanoma (Morpheus-Melanoma)
1 other identifier
interventional
110
5 countries
14
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Feb 2022
Typical duration for phase_1
14 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 22, 2021
CompletedFirst Posted
Study publicly available on registry
November 10, 2021
CompletedStudy Start
First participant enrolled
February 2, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 22, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
May 28, 2024
CompletedResults Posted
Study results publicly available
July 18, 2025
CompletedJuly 18, 2025
June 1, 2025
1.6 years
October 22, 2021
May 21, 2025
June 30, 2025
Conditions
Outcome Measures
Primary Outcomes (2)
Pathologic Response Rate (pRR) for Cohort 1 as Determined by Independent Pathologic Review
pRR was defined as the percentage of participants with pathologic complete response (pCR), pathologic near complete response (pnCR), and pathologic partial response (pPR) as determined by an independent pathologic review. pCR was defined as a complete absence of viable tumor cells, pnCR as \> 0 to ≤ 10% of viable tumor cells, and pPR was defined as \> 10 to ≤ 50% of viable tumor cells in the dissected lymph node. Participants with missing or no pathologic response assessment, including participants who did not proceed to complete lymph node dissection (CLND), were classified as non-responders. pRR was calculated for each arm along with 95% confidence intervals (CIs) using Clopper-Pearson method. The difference in pRR between the experimental arms and the control arm was calculated, along with 95% CIs using the Wald method with continuity correction.
Time of surgery (scheduled at Week 7)
Objective Response Rate (ORR) for Cohort 2 as Determined by the Investigator
ORR was defined as the percentage of participants with a complete response (CR) or partial response (PR) on two consecutive occasions ≥4 weeks apart, as determined by the investigator according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1). CR was defined as the disappearance of all target lesions or any pathological lymph nodes (whether target or non-target) having a reduction in the short axis to \<10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. Participants with missing or no response assessments were classified as non-responders. ORR was calculated for each arm, along with 95% CIs using Clopper-Pearson method.
From randomization up to approximately 3.6 months
Secondary Outcomes (16)
pRR for Cohort 1 as Determined by Local Pathologic Assessment
Time of surgery ( scheduled at Week 7)
Event-free Survival (EFS) for Cohort 1
From randomization to disease progression, disease recurrence or death or last tumor assessment (up to 22.51 months)
Relapse-free Survival (RFS) for Cohort 1
From surgery (scheduled at Week 7) to first documented disease recurrence or death or last tumor assessment (up to 20.9 months)
Overall Survival (OS) for Cohort 1
From randomization to death from any cause or last known to be alive (Up to 25 months)
ORR for Cohort 1
Prior to surgery (up to Week 6)
- +11 more secondary outcomes
Study Arms (7)
Cohort 1: Nivolumab + Ipilimumab
ACTIVE COMPARATORCohort 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.
Cohort 1: RO7247669 2100 mg
EXPERIMENTALCohort 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.
Cohort 1: + Atezolizumab + Tiragolumab
EXPERIMENTALCohort 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.
Cohort 1: RO7247669 2100 mg + Tiragolumab
EXPERIMENTALCohort 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.
Cohort 2: RO7247669 2100 mg + Tiragolumab
EXPERIMENTALCohort 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.
Cohort 1: RO7247669 600 mg
EXPERIMENTALCohort 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.
Cohort 1: RO7247669 600 mg + Tiragolumab
EXPERIMENTALCohort 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
Nivolumab will be administered at a dose of 3 mg/kg IV on Day 1 of each 21 day cycle.
Ipilimumab will be administered at a dose of 1 mg/kg by IV on Day 1 of each 21 day cycle.
RO7247669 will be administered at a dose of 2100 mg by IV infusion on Day 1 of each 21 day cycle.
Atezolizumab will be administered at a dose of 1200 mg IV on Day 1 of each 21 day cycle.
Tiragolumab will be administered at a dose of 600 mg IV on Day 1 of each 21 day cycle.
RO7247669 will be administered at a dose of 600 mg by IV infusion on Day 1 of each 21 day cycle.
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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
- 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
- +15 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (14)
City of Hope
Duarte, California, 91010, United States
The Angeles Clinic and Research Institute - W LA Office
Los Angeles, California, 90025, United States
Moffitt Cancer Center
Tampa, Florida, 33612, United States
MD Anderson Cancer Center
Houston, Texas, 77030, United States
Melanoma Institute Australia
North Sydney, New South Wales, 2060, Australia
Hopital de la Timone
Marseille, 13005, France
APHP - Hospital Saint Louis
Paris, 75475, France
Institut Universitaire du Cancer de Toulouse-Oncopole
Toulouse, 31059, France
Institut Gustave Roussy
Villejuif, 94805, France
Azienda Ospedaliera Universitaria Senese
Siena, Abruzzo, 53100, Italy
Istituto Nazionale Tumori Fondazione G. Pascale
Napoli, Campania, 80131, Italy
Istituto Europeo Di Oncologia
Milan, Lombardy, 20141, Italy
Ospedale S.Maria della Misericordia
Perugia, Umbria, 06132, Italy
Hospital Universitario Vall d Hebron
Barcelona, 08035, Spain
Related Publications (1)
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 Nov;31(11):3700-3712. doi: 10.1038/s41591-025-03967-2. Epub 2025 Sep 24.
PMID: 40993242DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Medical Communications
- Organization
- Hoffmann-La Roche
Study Officials
- STUDY DIRECTOR
Clinical Trials
Hoffmann-La Roche
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 22, 2021
First Posted
November 10, 2021
Study Start
February 2, 2022
Primary Completion
September 22, 2023
Study Completion
May 28, 2024
Last Updated
July 18, 2025
Results First Posted
July 18, 2025
Record last verified: 2025-06
Data Sharing
- IPD Sharing
- Will share
Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here ( https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research\_and\_development/who\_we\_are\_how\_we\_work/clinical\_trials/our\_commitment\_to\_data\_sharing.htm).