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

Melanoma Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05116202
• Other study ID #: BO43328
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: February 2, 2022
• Est. completion date: March 27, 2024

Study information

• Verified date: April 2024
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 110
• Est. completion date: March 27, 2024
• Est. primary completion date: September 22, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Melanoma

Intervention

Drug:
• Nivolumab
Nivolumab will be administered at a dose of 3 mg/kg IV on Day 1 of each 21 day cycle.
• Ipilimumab
Ipilimumab will be administered at a dose of 1 mg/kg by IV on Day 1 of each 21 day cycle.
• RO7247669 2100 mg
RO7247669 will be administered at a dose of 2100 mg by IV infusion on Day 1 of each 21 day cycle.
• Atezolizumab
Atezolizumab will be administered at a dose of 1200 mg IV on Day 1 of each 21 day cycle.
• Tiragolumab
Tiragolumab will be administered at a dose of 600 mg IV on Day 1 of each 21 day cycle.
• RO7247669 600 mg
RO7247669 will be administered at a dose of 600 mg by IV infusion on Day 1 of each 21 day cycle.

Locations

Country	Name	City	State
Australia	Linear Clinical Research Limited	Nedlands	Western Australia
Australia	Melanoma Institute Australia	North Sydney	New South Wales
France	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
Italy	Istituto Europeo Di Oncologia	Milano	Lombardia
Italy	Istituto Nazionale Tumori Fondazione G. Pascale	Napoli	Campania
Italy	Ospedale S.Maria della Misericordia	Perugia	Umbria
Italy	Azienda Ospedaliera Universitaria Senese	Siena	Abruzzo
Netherlands	Antoni van Leeuwenhoek Ziekenhuis	Amsterdam
Netherlands	Leids Universitair Medisch Centrum	Leiden
Spain	Hospital Universitario Vall d Hebron	Barcelona
Spain	Clinica Universidad de Navarra ; Servicio de Farmacia	Madrid
Spain	Hospital Universitario HM Sanchinarro-CIOCC	Madrid
Spain	Clinica Universidad de Navarra	Pamplona	Navarra
United States	City of Hope	Duarte	California
United States	MD Anderson Cancer Center	Houston	Texas
United States	The Angeles Clinic and Research Institute - W LA Office	Los Angeles	California
United States	Providence St Johns Health Center	Santa Monica	California
United States	Moffitt Cancer Center	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Australia,  France,  Italy,  Netherlands,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pathologic Response Rate (pRR) for Cohort 1 as Determined by Independent Pathologic Review	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.	Time of surgery (Week 7)
Primary	Objective Response Rate (ORR) for Cohort 2	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.	Enrollment/randomization up to approximately 5 years
Secondary	pRR for Cohort 1 as Determined by Local Pathologic Assessment	pRR is defined as the proportion of participants with pCR, pnCR, and pPR at time of surgery, as determined by local pathologic assessment.	Time of surgery (Week 7)
Secondary	Event-Free Survival (EFS) for Cohort 1	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.	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	Relapse-Free Survival (RFS) for Cohort 1	RFS is defined as the time from surgery to the first documented recurrence of disease or death from any cause.	Surgery to the first documented recurrence of disease or death from any cause (up to approximately 5 years)
Secondary	Overall Survival (OS) for Cohort 1	OS is defined as the time from randomization to death from any cause.	Randomization to death from any cause (up to approximately 5 years)
Secondary	Objective Response Rate (ORR) for Cohort 1	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.	Prior to surgery (up to Week 6)
Secondary	Percentage of Participants With Adverse Events for Cohort 1		Baseline through the end of the study (approximately 5 years)
Secondary	Percentage of Participants With Immune-Related Adverse Events for Cohort 1	Percentage of participants with immune-related adverse events Grade >= 3 during the first 12 weeks.	Baseline to Week 12
Secondary	Rate of Delayed Surgery Due to Treatment-Related Adverse Events for Cohort 1		Week 8 to Week 9
Secondary	Duration of Delayed Surgery Due to Treatment-Related Adverse Events for Cohort 1		Week 8 to Week 9
Secondary	Surgical Complication Rates for Cohort 1	Surgical complication rates according to Clavien-Dindo surgical classification after completion lymph node dissection (CLND).	Week 7 through Follow-Up (up to approximately 6 months)
Secondary	Progression-Free Survival (PFS) for Cohort 2	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.	Randomization/enrollment to the first occurrence of disease progression or death from any cause (whichever occurs first)(up to approximately 5 years)
Secondary	Overall Survival (OS) for Cohort 2	OS after randomization/enrollment, defined as the time from randomization/enrollment to death from any cause.	Randomization/enrollment to death from any cause (up to approximately 5 years)
Secondary	Overall Survival (OS) at Specific Timepoints for Cohort 2	OS after randomization/enrollment, defined as the time from randomization/enrollment to death from any cause.	Randomization/enrollment to death from any cause at specific timepoints (up to approximately 5 years)
Secondary	Duration of Response (DOR) for Cohort 2	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.	First occurrence of a documented objective response to disease progression or death from any cause (whichever occurs first)(up to approximately 5 years)
Secondary	Disease Control for Cohort 2	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.	Randomization up to approximately 5 years
Secondary	Percentage of Participants With Adverse Events for Cohort 2		Baseline through the end of the study (approximately 5 years)