Clinical trial NCT05116202: A Study Evaluating the Efficacy and Safety of Multiple Treatment Combinations in Patients With Melanoma (Morpheus-Melanoma)
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Melanoma
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2021-11-10
Enrollment: 110
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Pathologic Response Rate (pRR) for Cohort 1 as Determined by Independent Pathologic Review
timeFrame: Time of surgery (Week 7)
measure: Objective Response Rate (ORR) for Cohort 2
timeFrame: Enrollment/randomization up to approximately 5 years
Secondary outcomes:
measure: pRR for Cohort 1 as Determined by Local Pathologic Assessment
timeFrame: Time of surgery (Week 7)
measure: Event-Free Survival (EFS) for Cohort 1
timeFrame: 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)
measure: Relapse-Free Survival (RFS) for Cohort 1
timeFrame: Surgery to the first documented recurrence of disease or death from any cause (up to approximately 5 years)
measure: Overall Survival (OS) for Cohort 1
timeFrame: Randomization to death from any cause (up to approximately 5 years)
measure: Objective Response Rate (ORR) for Cohort 1
timeFrame: Prior to surgery (up to Week 6)
measure: Percentage of Participants With Adverse Events for Cohort 1
timeFrame: Baseline through the end of the study (approximately 5 years)
measure: Percentage of Participants With Immune-Related Adverse Events for Cohort 1
timeFrame: Baseline to Week 12
measure: Rate of Delayed Surgery Due to Treatment-Related Adverse Events for Cohort 1
timeFrame: Week 8 to Week 9
measure: Duration of Delayed Surgery Due to Treatment-Related Adverse Events for Cohort 1
timeFrame: Week 8 to Week 9
measure: Surgical Complication Rates for Cohort 1
timeFrame: Week 7 through Follow-Up (up to approximately 6 months)
measure: Progression-Free Survival (PFS) for Cohort 2
timeFrame: Randomization/enrollment to the first occurrence of disease progression or death from any cause (whichever occurs first)(up to approximately 5 years)
measure: Overall Survival (OS) for Cohort 2
timeFrame: Randomization/enrollment to death from any cause (up to approximately 5 years)
measure: Overall Survival (OS) at Specific Timepoints for Cohort 2
timeFrame: Randomization/enrollment to death from any cause at specific timepoints (up to approximately 5 years)
measure: Duration of Response (DOR) for Cohort 2
timeFrame: First occurrence of a documented objective response to disease progression or death from any cause (whichever occurs first)(up to approximately 5 years)
measure: Disease Control for Cohort 2
timeFrame: Randomization up to approximately 5 years
measure: Percentage of Participants With Adverse Events for Cohort 2
timeFrame: Baseline through the end of the study (approximately 5 years)
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope
state: California
city: Los Angeles
country: United States
facility: The Angeles Clinic and Research Institute - W LA Office
state: California
city: Santa Monica
country: United States
facility: Providence St Johns Health Center
state: California
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: North Sydney
country: Australia
facility: Melanoma Institute Australia
state: New South Wales
city: Nedlands
country: Australia
facility: Linear Clinical Research Limited
state: Western Australia
city: Marseille
country: France
facility: Hopital de la Timone
city: Paris
country: France
facility: APHP - Hospital Saint Louis
city: Toulouse
country: France
facility: Institut Universitaire du Cancer de Toulouse-Oncopole
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Siena
country: Italy
facility: Azienda Ospedaliera Universitaria Senese
state: Abruzzo
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori Fondazione G. Pascale
state: Campania
city: Milano
country: Italy
facility: Istituto Europeo Di Oncologia
state: Lombardia
city: Perugia
country: Italy
facility: Ospedale S.Maria della Misericordia
state: Umbria
city: Amsterdam
country: Netherlands
facility: Antoni van Leeuwenhoek Ziekenhuis
city: Leiden
country: Netherlands
facility: Leids Universitair Medisch Centrum
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra
state: Navarra
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d Hebron
city: Madrid
country: Spain
facility: Clinica Universidad de Navarra ; Servicio de Farmacia
city: Madrid
country: Spain
facility: Hospital Universitario HM Sanchinarro-CIOCC
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: