This study will evaluate the efficacy and safety of cobimetinib plus atezolizumab in participants with BRAFV600 wild-type melanoma with central nervous system (CNS) metastases and of cobimetinib plus atezolizumab and vemurafenib in BRAFV600 mutation-positive melanoma patients with CNS metastases.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
80
60 mg (three tablets of 20 mg each) orally (PO) once a day (QD) on Days 1-21 of each 28-day cycle.
Atezolizumab will be given at a fixed dose of 840 mg by intravenous (IV) infusion on Days 1 and 15 of each 28-day cycle. Only for cohort 2, no dose of atezolizumab will be given during the run-in period (cycle 1).
Participants will receive vemurafenib 960 mg (four 240 mg tablets) orally (PO) twice daily (BID) on days 1-21 of the run-in period (cycle 1); thereafter, they will receive vemurafenib 720 mg dose (three 240 mg tablets) PO BID on days 22-28 of cycle 1 and on days 1-28 of all subsequent cycles.
Instituto Nacional de Cancer - INCa; Oncologia
Rio de Janeiro, Rio de Janeiro, Brazil
Oncosite - Centro de Pesquisa Clinica Em Oncologia Ltda
Ijuí, Rio Grande do Sul, Brazil
Hospital das Clinicas - UFRGS
Porto Alegre, Rio Grande do Sul, Brazil
CHU de Nantes; Cancéro-dermatologie
Nantes, France
Institut Claudius Regaud; Departement Oncologie Medicale
Toulouse, France
Institut Gustave Roussy; Dermatologie
Villejuif, France
Universitätsklinikum "Carl Gustav Carus"; Klinik und Poliklinik fur Dermatologie
Dresden, Germany
Orszagos Onkologiai Intezet; Borgyogyaszati Osztaly
Budapest, Hungary
IRCCS Istituto Nazionale Tumori Fondazione Pascale; Oncologia Medica B
Naples, Campania, Italy
Istituto Dermopatico dell'Immacolata (IDI)-IRCCS; IV Divisione Oncologica e Dermatologia Oncologica
Rome, Lazio, Italy
...and 12 more locations
Intracranial Objective Response Rate (ORR)
Intracranial ORR is defined as the percentage of participants with either a complete response (CR) or a partial response (PR) in their intracranial disease based on two consecutive assessments \>= 4 weeks apart. Disease status for this endpoint will be determined by an Independent Review Committee (IRC) in accordance with Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) with modified measurability definition for intracranial lesions (\>= 0.5 cm by MRI) and allowing up to five intracranial target lesions. CR is defined as disappearance of all lesions. PR is defined as \>=30% decrease in tumor burden, in the absence of CR. The primary endpoint is analyzed on the BRAFV600 mutation positive (Cohort 2) only as the Sponsor had discontinued enrolment into Cohort 1. Data for Cohort 1 was not collected nor analyzed for this outcome measure.
Time frame: Baseline up to cut of date (approximately 2.5 years)
Extracranial ORR
Extracranial ORR, defined as the percentage of participants with either a CR or PR in their extracranial disease based on two consecutive assessments \>=4 weeks apart, as determined by the investigator according to RECIST v1.1.
Time frame: Baseline up to cut of date (approximately 2.5 years)
Overall ORR
Overall ORR, defined as the percentage of participants with either a CR or PR in their overall disease (i.e. including intracranial and extracranial disease) based on two consecutive assessments \>= 4 weeks apart, as determined by the investigator according to RECIST v1.1. CR was defined as disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker levels. PR was defined as at least a 30 percent (%) decrease in sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR.
Time frame: Baseline up to cut of date (approximately 2.5 years)
Progression-Free Survival (PFS)
Intracranial, extracranial and overall PFS defined as the time from study treatment initiation 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.
Time frame: Baseline up to cut of date (approximately 2.5 years)
Duration of Response (DOR)
Intracranial, extracranial and overall DOR, defined as the time from the first occurrence of a documented objective response based on two consecutive assessments ≥ 4 weeks apart to disease progression or death from any cause (whichever occurs first), as determined by the investigator according to RECIST v1.1. This endpoint is analyzed on the BRAFV600 mutation positive (Cohort 2) only as the Sponsor had discontinued enrolment into Cohort 1. Data for Cohort 1 was not collected nor analyzed for this outcome measure.
Time frame: Baseline up to cut of date (approximately 2.5 years)
Disease Control Rate (DCR)
Intracranial, extracranial and overall DCR, defined as the percentage of participants with a CR or PR or stable disease (SD) at 16 weeks from study treatment initiation, as determined by the investigator according to RECIST v1.1. CR was defined as disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker levels. PR was defined as at least a 30 percent (%) decrease in sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. SD is defined as neither sufficient shrinkage to qualify for CR or PR nor sufficient increase to qualify for disease progression. Disease progression is defined as \>=20% increase in tumor burden. This endpoint is analyzed on the BRAFV600 mutation positive (Cohort 2) only as the Sponsor had discontinued enrolment into Cohort 1. Data for Cohort 1 was not collected nor analyzed for this outcome measure.
Time frame: At 16 weeks
Overall Survival (OS)
OS is defined as the time from study treatment initiation to death from any cause.
Time frame: Baseline up to 4 years, 4 months
Time to Cognitive Symptom Deterioration
Time from study treatment initiation to cognitive symptom deterioration, defined as a change (\>= 10 points on a 0-100 scale) on selected scales of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-BN20) (visual disorder, motor dysfunction, communication deficit, headaches, seizures and drowsiness).
Time frame: Up to 48 months
Time to Symptom and Function Deterioration
Time from study treatment initiation to symptom and function deterioration defined as a change (\>= 10 points on a 0-100 scale) in fatigue, physical functioning, cognitive functioning, or role functioning as measured by the Fatigue, Physical, Cognitive, Role Functioning scales of the EORTC QLQ-C30.
Time frame: Up to 48 months
Duration of Stable/Improved Health-related Quality of Life (HRQoL) Scores
Duration of Stable/Improved HRQoL scores as assessed through use of the two-item Global Health Status (GHS)/HRQoL subscale (Questions 29 and 30) of the EORTC QLQ-C30.
Time frame: Baseline up to cut of date (approximately 2.5 years)
Percentage of Participants With Adverse Events
The safety profile of Cobimetinib plus Atezolizumab and Cobimetinib plus Atezolizumab plus Vemurafenib is evaluated in terms of occurrence and severity of AEs. Severity will be determined according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0)
Time frame: Baseline up to 4 years, 4 months
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.