A Study Evaluating the Efficacy and Safety of Multiple Treatment Combinations in Patients With Melanoma (Morpheus-Melanoma)
- Conditions
- Melanoma
- Interventions
- Drug: RO7247669 600 mgDrug: RO7247669 2100 mg
- Registration Number
- NCT05116202
- Lead Sponsor
- Hoffmann-La Roche
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 110
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cohort 1: RO7247669 600 mg 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. Cohort 1: RO7247669 600 mg + Tiragolumab RO7247669 600 mg 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. Cohort 1: RO7247669 2100 mg + Tiragolumab RO7247669 2100 mg 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. Cohort 2: RO7247669 2100 mg + Tiragolumab RO7247669 2100 mg 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. Cohort 1: Nivolumab + Ipilimumab 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. Cohort 1: RO7247669 2100 mg + Tiragolumab 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. Cohort 2: RO7247669 2100 mg + Tiragolumab 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. Cohort 1: + Atezolizumab + Tiragolumab Atezolizumab 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. Cohort 1: + Atezolizumab + Tiragolumab 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. Cohort 1: Nivolumab + Ipilimumab Nivolumab 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. Cohort 1: RO7247669 2100 mg 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. Cohort 1: RO7247669 600 mg + Tiragolumab 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.
- Primary Outcome Measures
Name Time Method Objective Response Rate (ORR) for Cohort 2 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.
Pathologic Response Rate (pRR) for Cohort 1 as Determined by Independent Pathologic Review 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.
- Secondary Outcome Measures
Name Time Method Event-Free Survival (EFS) for Cohort 1 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.
pRR for Cohort 1 as Determined by Local Pathologic Assessment 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.
Percentage of Participants With Adverse Events for Cohort 1 Baseline through the end of the study (approximately 5 years) Percentage of Participants With Immune-Related Adverse Events for Cohort 1 Baseline to Week 12 Percentage of participants with immune-related adverse events Grade \>= 3 during the first 12 weeks.
Objective Response Rate (ORR) for Cohort 1 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.
Rate of Delayed Surgery Due to Treatment-Related Adverse Events for Cohort 1 Week 8 to Week 9 Relapse-Free Survival (RFS) for Cohort 1 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.
Overall Survival (OS) for Cohort 1 Randomization to death from any cause (up to approximately 5 years) OS is defined as the time from randomization to death from any cause.
Surgical Complication Rates for Cohort 1 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).
Progression-Free Survival (PFS) for Cohort 2 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.
Overall Survival (OS) for Cohort 2 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.
Duration of Response (DOR) for Cohort 2 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.
Percentage of Participants With Adverse Events for Cohort 2 Baseline through the end of the study (approximately 5 years) Duration of Delayed Surgery Due to Treatment-Related Adverse Events for Cohort 1 Week 8 to Week 9 Disease Control for Cohort 2 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.
Overall Survival (OS) at Specific Timepoints for Cohort 2 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.
Trial Locations
- Locations (21)
Melanoma Institute Australia
🇦🇺North Sydney, New South Wales, Australia
The Angeles Clinic and Research Institute - W LA Office
🇺🇸Los Angeles, California, United States
Ospedale S.Maria della Misericordia
🇮🇹Perugia, Umbria, Italy
Institut Gustave Roussy
🇫🇷Villejuif, France
Leids Universitair Medisch Centrum
🇳🇱Leiden, Netherlands
APHP - Hospital Saint Louis
🇫🇷Paris, France
Hopital de la Timone
🇫🇷Marseille, France
Linear Clinical Research Limited
🇦🇺Nedlands, Western Australia, Australia
Hospital Universitario HM Sanchinarro-CIOCC
🇪🇸Madrid, Spain
Clinica Universidad de Navarra ; Servicio de Farmacia
🇪🇸Madrid, Spain
Moffitt Cancer Center
🇺🇸Tampa, Florida, United States
MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Providence St Johns Health Center
🇺🇸Santa Monica, California, United States
City of Hope
🇺🇸Duarte, California, United States
Istituto Nazionale Tumori Fondazione G. Pascale
🇮🇹Napoli, Campania, Italy
Institut Universitaire du Cancer de Toulouse-Oncopole
🇫🇷Toulouse, France
Istituto Europeo Di Oncologia
🇮🇹Milano, Lombardia, Italy
Clinica Universidad de Navarra
🇪🇸Pamplona, Navarra, Spain
Hospital Universitario Vall d Hebron
🇪🇸Barcelona, Spain
Azienda Ospedaliera Universitaria Senese
🇮🇹Siena, Abruzzo, Italy
Antoni van Leeuwenhoek Ziekenhuis
🇳🇱Amsterdam, Netherlands