A Study Evaluating the Safety and Efficacy of Cobimetinib Plus Atezolizumab in BRAFV600 Wild-type Melanoma With Central Nervous System Metastases and Cobimetinib Plus Atezolizumab and Vemurafenib in BRAFV600 Mutation-positive Melanoma With Central Nervous System Metastases

NCT03625141 | Completed Phase 2 Results DMC

• 2 other identifiers: MO391362018-000759-41
• Study Type: interventional
• Target: 80
• Locations: 8 countries
• Sites: 22

Brief Summary

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.

Conditions

Metastatic Melanoma

Outcome Measures

Primary Outcomes (1)

• 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.

  Baseline up to cut of date (approximately 2.5 years)

Secondary Outcomes (10)

• Extracranial ORR

  Baseline up to cut of date (approximately 2.5 years)

• Overall ORR

  Baseline up to cut of date (approximately 2.5 years)

• Progression-Free Survival (PFS)

  Baseline up to cut of date (approximately 2.5 years)

• Duration of Response (DOR)

  Baseline up to cut of date (approximately 2.5 years)

• Disease Control Rate (DCR)

  At 16 weeks

Study Arms (2)

Cohort 1- cobimetinib and atezolizumab

EXPERIMENTAL

Participants with BRAFV600 wild-type disease will be administered cobimetinib on Days 1-21 of each 28-day cycle; and atezolizumab on Days 1 and 15 of each treatment cycle.

Drug: Cobimetinib; Drug: Atezolizumab

Cohort 2 - cobimetinib, atezolizumab and vemurafenib

EXPERIMENTAL

Participants with BRAFV600 mutation-positive disease will be administered cobimetinib, atezolizumab and vemurafenib in 28-day treatment cycles. Treatment includes a 28-day run-in period where participants will receive cobimetinib and vemurafenib only. Upon completion of the 28-day run-in period, atezolizumab will be added to their treatment regimen.

Drug: Cobimetinib; Drug: Atezolizumab; Drug: Vemurafenib

Interventions

Cobimetinib DRUG

60 mg (three tablets of 20 mg each) orally (PO) once a day (QD) on Days 1-21 of each 28-day cycle.

Also known as: Cotellic

Cohort 1- cobimetinib and atezolizumab; Cohort 2 - cobimetinib, atezolizumab and vemurafenib

Atezolizumab DRUG

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).

Also known as: Tecentriq

Cohort 1- cobimetinib and atezolizumab; Cohort 2 - cobimetinib, atezolizumab and vemurafenib

Vemurafenib DRUG

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.

Also known as: Zelboraf

Cohort 2 - cobimetinib, atezolizumab and vemurafenib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed melanoma with radiologically confirmed brain metastases
• Documented BRAFV600 mutation status of melanoma tumour tissue using a validated genetic test.
• Measurable brain metastases

You may not qualify if:

• Prior SRT or surgical therapy of ≤ 10 brain metastases is allowed but prior WBRT is not allowed
• Adverse effects of all prior systemic or local treatment must have either returned to baseline or become stable and manageable prior to initiation of study treatment.
• Age ≥18 years
• Able to comply with the study protocol, in the investigator's judgment
• ECOG Performance Status ≤ 2
• Life expectancy of \> 3 months
• Willing and able to complete health and quality of life questionnaires required by the protocol
• Adequate hematologic and end-organ function
• Female patients of childbearing potential and male patients with partners of childbearing potential must agree to always use two effective forms of contraception during the course of this study and for at least six months after completion of study therapy.
• Male patients must agree to refrain from donating sperm for at least six months after the last dose of cobimetinib
• Ocular melanoma
• Leptomeningeal involvement
• Uncontrolled tumour-related pain
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage more than once every 28 days.
• Prior WBRT treatment for CNS disease

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (22)

Instituto Nacional de Cancer - INCa; Oncologia

Rio de Janeiro, Rio de Janeiro, 20560-120, Brazil

Location

Oncosite - Centro de Pesquisa Clinica Em Oncologia Ltda

Ijuí, Rio Grande do Sul, 98700-000, Brazil

Location

Hospital das Clinicas - UFRGS

Porto Alegre, Rio Grande do Sul, 90035-903, Brazil

Location

CHU de Nantes; Cancéro-dermatologie

Nantes, 44093, France

Location

Institut Claudius Regaud; Departement Oncologie Medicale

Toulouse, 31059, France

Location

Institut Gustave Roussy; Dermatologie

Villejuif, 94805, France

Location

Universitätsklinikum "Carl Gustav Carus"; Klinik und Poliklinik fur Dermatologie

Dresden, 01307, Germany

Location

Orszagos Onkologiai Intezet; Borgyogyaszati Osztaly

Budapest, 1122, Hungary

Location

IRCCS Istituto Nazionale Tumori Fondazione Pascale; Oncologia Medica B

Napoli, Campania, 80131, Italy

Location

Istituto Dermopatico dell'Immacolata (IDI)-IRCCS; IV Divisione Oncologica e Dermatologia Oncologica

Rome, Lazio, 00167, Italy

Location

IRCCS Istituto Nazionale Per La Ricerca Sul Cancro (IST); Oncologia Medica A

Genoa, Liguria, 16132, Italy

Location

Irccs Istituto Europeo Di Oncologia (IEO); Oncologia Medica

Milan, Lombardy, 20141, Italy

Location

Azienda Ospedaliero - Universitaria Pisana U.O. Oncologia Medica 2 Universitaria ? Polo Oncologico

Pisa, Tuscany, 56126, Italy

Location

IOV - Istituto Oncologico Veneto IRCCS

Padua, Veneto, 35128, Italy

Location

Riga East Clinical University Hospital Latvian Oncology Centre

Riga, LV-1079, Latvia

Location

Onkologikoa - Instituto Oncológico de Donostia

Donostia / San Sebastian, Guipuzcoa, 20014, Spain

Location

Hospital Clínic i Provincial; Servicio de Hematología y Oncología

Barcelona, 08036, Spain

Location

Institut Catala d Oncologia Hospital Duran i Reynals

Barcelona, 08908, Spain

Location

Hospital General Universitario Gregorio Marañon; Servicio de Oncologia

Madrid, 28007, Spain

Location

Hospital Universitario Virgen Macarena; Servicio de Oncologia

Seville, 41009, Spain

Location

Hospital General Universitario de Valencia; Servicio de oncologia

Valencia, 46014, Spain

Location

Universitätsspital Zürich; USZ Flughafen / H13-7-609

Zurich, 8091, Switzerland

Location

Related Publications (2)

• Dummer R, Queirolo P, Gerard Duhard P, Hu Y, Wang D, de Azevedo SJ, Robert C, Ascierto PA, Chiarion-Sileni V, Pronzato P, Spagnolo F, Mujika Eizmendi K, Liszkay G, de la Cruz Merino L, Tawbi H. Atezolizumab, vemurafenib, and cobimetinib in patients with melanoma with CNS metastases (TRICOTEL): a multicentre, open-label, single-arm, phase 2 study. Lancet Oncol. 2023 Dec;24(12):e461-e471. doi: 10.1016/S1470-2045(23)00334-0. Epub 2023 Jul 14.

  PMID: 37459873 DERIVED

• Dummer R, Queirolo P, Abajo Guijarro AM, Hu Y, Wang D, de Azevedo SJ, Robert C, Ascierto PA, Chiarion-Sileni V, Pronzato P, Spagnolo F, Mujika Eizmendi K, Liszkay G, de la Cruz Merino L, Tawbi H. Atezolizumab, vemurafenib, and cobimetinib in patients with melanoma with CNS metastases (TRICOTEL): a multicentre, open-label, single-arm, phase 2 study. Lancet Oncol. 2022 Sep;23(9):1145-1155. doi: 10.1016/S1470-2045(22)00452-1. Epub 2022 Aug 5.

  PMID: 35940183 DERIVED

MeSH Terms

Conditions

Melanoma

Interventions

cobimetinib; atezolizumab; Vemurafenib

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Limitations and Caveats

The Sponsor decided to discontinue enrollment into Cohort 1, which was communicated in a Dear Investigator Letter dated 9 July 2019.

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800-821-8590

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 2, 2018
• First Posted: August 10, 2018
• Study Start: December 13, 2018
• Primary Completion: June 7, 2021
• Study Completion: April 13, 2023
• Last Updated: April 11, 2024
• Results First Posted: February 8, 2024

Record last verified: 2024-04

Locations

BR (3); HU (1); IT (6); LA (1); ES (6); FR (3); CH (1); DE (1)