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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05116202




Registration number
NCT05116202
Ethics application status
Date submitted
22/10/2021
Date registered
10/11/2021

Titles & IDs
Public title
A Study Evaluating the Efficacy and Safety of Multiple Treatment Combinations in Patients With Melanoma (Morpheus-Melanoma)
Scientific 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)
Secondary ID [1] 0 0
BO43328
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Melanoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Malignant melanoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Nivolumab
Treatment: Drugs - Ipilimumab
Treatment: Drugs - RO7247669 2100 mg
Treatment: Drugs - Atezolizumab
Treatment: Drugs - Tiragolumab
Treatment: Drugs - RO7247669 600 mg

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.


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

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

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

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

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

Treatment: Drugs: 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 code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Pathologic Response Rate (pRR) for Cohort 1 as Determined by Independent Pathologic Review
Timepoint [1] 0 0
Time of surgery (Week 7)
Primary outcome [2] 0 0
Objective Response Rate (ORR) for Cohort 2
Timepoint [2] 0 0
Enrollment/randomization up to approximately 5 years
Secondary outcome [1] 0 0
pRR for Cohort 1 as Determined by Local Pathologic Assessment
Timepoint [1] 0 0
Time of surgery (Week 7)
Secondary outcome [2] 0 0
Event-Free Survival (EFS) for Cohort 1
Timepoint [2] 0 0
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)
Secondary outcome [3] 0 0
Relapse-Free Survival (RFS) for Cohort 1
Timepoint [3] 0 0
Surgery to the first documented recurrence of disease or death from any cause (up to approximately 5 years)
Secondary outcome [4] 0 0
Overall Survival (OS) for Cohort 1
Timepoint [4] 0 0
Randomization to death from any cause (up to approximately 5 years)
Secondary outcome [5] 0 0
Objective Response Rate (ORR) for Cohort 1
Timepoint [5] 0 0
Prior to surgery (up to Week 6)
Secondary outcome [6] 0 0
Percentage of Participants With Adverse Events for Cohort 1
Timepoint [6] 0 0
Baseline through the end of the study (approximately 5 years)
Secondary outcome [7] 0 0
Percentage of Participants With Immune-Related Adverse Events for Cohort 1
Timepoint [7] 0 0
Baseline to Week 12
Secondary outcome [8] 0 0
Rate of Delayed Surgery Due to Treatment-Related Adverse Events for Cohort 1
Timepoint [8] 0 0
Week 8 to Week 9
Secondary outcome [9] 0 0
Duration of Delayed Surgery Due to Treatment-Related Adverse Events for Cohort 1
Timepoint [9] 0 0
Week 8 to Week 9
Secondary outcome [10] 0 0
Surgical Complication Rates for Cohort 1
Timepoint [10] 0 0
Week 7 through Follow-Up (up to approximately 6 months)
Secondary outcome [11] 0 0
Progression-Free Survival (PFS) for Cohort 2
Timepoint [11] 0 0
Randomization/enrollment to the first occurrence of disease progression or death from any cause (whichever occurs first)(up to approximately 5 years)
Secondary outcome [12] 0 0
Overall Survival (OS) for Cohort 2
Timepoint [12] 0 0
Randomization/enrollment to death from any cause (up to approximately 5 years)
Secondary outcome [13] 0 0
Overall Survival (OS) at Specific Timepoints for Cohort 2
Timepoint [13] 0 0
Randomization/enrollment to death from any cause at specific timepoints (up to approximately 5 years)
Secondary outcome [14] 0 0
Duration of Response (DOR) for Cohort 2
Timepoint [14] 0 0
First occurrence of a documented objective response to disease progression or death from any cause (whichever occurs first)(up to approximately 5 years)
Secondary outcome [15] 0 0
Disease Control for Cohort 2
Timepoint [15] 0 0
Randomization up to approximately 5 years
Secondary outcome [16] 0 0
Percentage of Participants With Adverse Events for Cohort 2
Timepoint [16] 0 0
Baseline through the end of the study (approximately 5 years)

Eligibility
Key inclusion 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
2/02/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
28/05/2024
Sample size
Target
Accrual to date
Final
110
Recruitment in Australia
Recruitment state(s)
NSW,WA
Recruitment hospital [1] 0 0
Melanoma Institute Australia - North Sydney
Recruitment hospital [2] 0 0
Linear Clinical Research Limited - Nedlands
Recruitment postcode(s) [1] 0 0
2060 - North Sydney
Recruitment postcode(s) [2] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Texas
Country [4] 0 0
France
State/province [4] 0 0
Marseille
Country [5] 0 0
France
State/province [5] 0 0
Paris
Country [6] 0 0
France
State/province [6] 0 0
Toulouse
Country [7] 0 0
France
State/province [7] 0 0
Villejuif
Country [8] 0 0
Italy
State/province [8] 0 0
Abruzzo
Country [9] 0 0
Italy
State/province [9] 0 0
Campania
Country [10] 0 0
Italy
State/province [10] 0 0
Lombardia
Country [11] 0 0
Italy
State/province [11] 0 0
Umbria
Country [12] 0 0
Netherlands
State/province [12] 0 0
Amsterdam
Country [13] 0 0
Netherlands
State/province [13] 0 0
Leiden
Country [14] 0 0
Spain
State/province [14] 0 0
Navarra
Country [15] 0 0
Spain
State/province [15] 0 0
Barcelona
Country [16] 0 0
Spain
State/province [16] 0 0
Madrid

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
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).
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT05116202