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

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ClinicalTrials.gov Identifier: NCT05116202
Recruitment Status : Recruiting
First Posted : November 10, 2021
Last Update Posted : November 13, 2023
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Study Description
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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.

Condition or disease Intervention/treatment Phase
Melanoma Drug: Nivolumab Drug: Ipilimumab Drug: RO7247669 2100 mg Drug: Atezolizumab Drug: Tiragolumab Drug: RO7247669 600 mg Phase 1 Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 336 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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)
Actual Study Start Date : February 2, 2022
Estimated Primary Completion Date : January 19, 2025
Estimated Study Completion Date : July 19, 2025

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Melanoma
MedlinePlus related topics: Melanoma

Arms and Interventions
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Arm Intervention/treatment
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.
 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.
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.
 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.
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.
 Drug: Atezolizumab
Atezolizumab will be administered at a dose of 1200 mg IV on Day 1 of each 21 day cycle.
Other Name: Tecentriq, RO5541267

Drug: Tiragolumab
Tiragolumab will be administered at a dose of 600 mg IV on Day 1 of each 21 day cycle.
Other Name: RO7092284
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.
 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: Tiragolumab
Tiragolumab will be administered at a dose of 600 mg IV on Day 1 of each 21 day cycle.
Other Name: RO7092284
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.
 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: Tiragolumab
Tiragolumab will be administered at a dose of 600 mg IV on Day 1 of each 21 day cycle.
Other Name: RO7092284
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.
 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.
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.
 Drug: Tiragolumab
Tiragolumab will be administered at a dose of 600 mg IV on Day 1 of each 21 day cycle.
Other Name: RO7092284

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.


Outcome Measures
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Primary Outcome Measures :
  1. Pathologic Response Rate (pRR) for Cohort 1 as Determined by Independent Pathologic Review [ Time Frame: Time of surgery (Week 7) ]
    pRR is defined as the proportion of participants with pathologic complete response (pCR), pathologic near complete response (pnCR), and pathologic partial response (pPR) at time of surgery, as determined by independent pathologic review.

  2. Objective Response Rate (ORR) for Cohort 2 [ Time Frame: Enrollment/randomization up to approximately 5 years ]
    ORR is defined as the proportion 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 RECIST v1.1.


Secondary Outcome Measures :
  1. pRR for Cohort 1 as Determined by Local Pathologic Assessment [ Time Frame: Time of surgery (Week 7) ]
    pRR is defined as the proportion of participants with pCR, pnCR, and pPR at time of surgery, as determined by local pathologic assessment.

  2. Event-Free Survival (EFS) for Cohort 1 [ Time Frame: Randomization to disease progression that precludes surgery; local, regional or distant disease recurrence; or death from any cause (whichever occurs first) (up to approximately 5 years) ]
    EFS is defined as the time from randomization to any of the following events (whichever occurs first): Disease progression that precludes surgery, as assessed by the investigator according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1); local, regional or distant disease recurrence; or death from any cause.

  3. Relapse-Free Survival (RFS) for Cohort 1 [ Time Frame: Surgery to the first documented recurrence of disease or death from any cause (up to approximately 5 years) ]
    RFS is defined as the time from surgery to the first documented recurrence of disease or death from any cause.

  4. Overall Survival (OS) for Cohort 1 [ Time Frame: Randomization to death from any cause (up to approximately 5 years) ]
    OS is defined as the time from randomization to death from any cause.

  5. Objective Response Rate (ORR) for Cohort 1 [ Time Frame: Prior to surgery (up to Week 6) ]
    ORR is defined as the proportion of participants with a complete response (CR) or partial response (PR) as determined by the investigator according to RECIST v1.1, prior to surgery.

  6. Percentage of Participants With Adverse Events for Cohort 1 [ Time Frame: Baseline through the end of the study (approximately 5 years) ]
  7. Percentage of Participants With Immune-Related Adverse Events for Cohort 1 [ Time Frame: Baseline to Week 12 ]
    Percentage of participants with immune-related adverse events Grade >= 3 during the first 12 weeks.

  8. Rate of Delayed Surgery Due to Treatment-Related Adverse Events for Cohort 1 [ Time Frame: Week 8 to Week 9 ]
  9. Duration of Delayed Surgery Due to Treatment-Related Adverse Events for Cohort 1 [ Time Frame: Week 8 to Week 9 ]
  10. Surgical Complication Rates for Cohort 1 [ Time Frame: Week 7 through Follow-Up (up to approximately 6 months) ]
    Surgical complication rates according to Clavien-Dindo surgical classification after completion lymph node dissection (CLND).

  11. Progression-Free Survival (PFS) for Cohort 2 [ Time Frame: Randomization/enrollment to the first occurrence of disease progression or death from any cause (whichever occurs first)(up to approximately 5 years) ]
    PFS after randomization/enrollment, defined as the time from randomization/enrollment to the first occurrence of disease progression or death from any cause (whichever occurs first), as determined by the investigator according to RECIST v1.1.

  12. Overall Survival (OS) for Cohort 2 [ Time Frame: Randomization/enrollment to death from any cause (up to approximately 5 years) ]
    OS after randomization/enrollment, defined as the time from randomization/enrollment to death from any cause.

  13. Overall Survival (OS) at Specific Timepoints for Cohort 2 [ Time Frame: Randomization/enrollment to death from any cause at specific timepoints (up to approximately 5 years) ]
    OS after randomization/enrollment, defined as the time from randomization/enrollment to death from any cause.

  14. Duration of Response (DOR) for Cohort 2 [ Time Frame: First occurrence of a documented objective response to disease progression or death from any cause (whichever occurs first)(up to approximately 5 years) ]
    DOR is defined as the time from the first occurrence of a documented objective response to disease progression or death from any cause (whichever occurs first), as determined by the investigator according to RECIST v1.1.

  15. Disease Control for Cohort 2 [ Time Frame: Randomization up to approximately 5 years ]
    Disease control is defined as stable disease for >= 12 weeks or a CR or PR, as determined by the investigator according to RECIST v1.1.

  16. Percentage of Participants With Adverse Events for Cohort 2 [ Time Frame: Baseline through the end of the study (approximately 5 years) ]

Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05116202


Contacts
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Contact: Reference Study ID Number: BO43328 https://forpatients.roche.com/ 888-662-6728 (U.S. and Canada) global.rochegenentechtrials@roche.com

Locations
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Sponsors and Collaborators
Hoffmann-La Roche
Investigators
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Study Director: Clinical Trials Hoffmann-La Roche
More Information
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Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT05116202    
Other Study ID Numbers: BO43328
First Posted: November 10, 2021    Key Record Dates
Last Update Posted: November 13, 2023
Last Verified: November 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: 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).

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
 Nivolumab
Ipilimumab
Atezolizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immune Checkpoint Inhibitors
Molecular Mechanisms of Pharmacological Action