Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Symptoms and General Pathology

Nervous System Diseases

Rare Diseases

Melanoma

Neoplasm Metastasis

Melanoma, Cutaneous Malignant

Brain Neoplasms

Skin Neoplasms

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Diseases

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Neuroendocrine Tumor

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Bevacizumab

Atezolizumab

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Immunoglobulin G

Endothelial Growth Factors

Mitogens

Immunoglobulins, Intravenous

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

Immunologic Factors

Immune Checkpoint Inhibitors

Participants receive atezolizumab IV over 30-60 minutes and bevacizumab IV over 30-90 minutes on day 1. Cycles repeat every 14 days in the absence of disease progression or unacceptable toxicity.

Patients receive atezolizumab IV over 30-60 minutes and bevacizumab IV over 30-90 minutes on day 1. Cycles with atezolizumab and bevacizumab repeat every 14 days in the absence of disease progression or unacceptable toxicity. Patients also receive cobimetinib PO TID on days 1-21. Cycles with cobimetinib repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Cobimetinib

Quality-of-Life Assessment

Hussein A Tawbi

This phase II trial studies how well bevacizumab and atezolizumab with or without cobimetinib work in treating patients with untreated melanoma that has spread to the brain (brain metastases). Monoclonal antibodies, such as bevacizumab and atezolizumab, may interfere with the ability of tumor cells to grow and spread. Cobimetinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known if giving bevacizumab and atezolizumab with or without cobimetinib will work better in treating patients with melanoma brain metastases.

PRIMARY OBJECTIVES:

I. To determine the objective intracranial response rate of the combination of bevacizumab and atezolizumab in patients with active melanoma brain metastases (MBM) as measured by a modified immunotherapy Response Assessment in Neuro-oncology (iRANO) criteria measured by magnetic resonance imaging (MRI) of the brain.

II. To assess the safety, tolerability, and preliminary efficacy of the triplet combination of atezolizumab (Tencentriq), bevacizumab (Avastin), and cobimetinib (Cotellic). (TACo)

SECONDARY OBJECTIVES:

I. Safety and tolerability of bevacizumab + atezolizumab. II. Safety and tolerability of the combination of atezolizumab + bevacizumab + cobimetinib in patients with BRAFV600 wild-type metastatic melanoma to the brain who've experienced prior progression on anti-PD1.

III. Overall response rates (intracranial + extracranial) using a modified version of iRANO and compared to modified Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and Response Assessment in Neuro-oncology - Brain Metastases (RANO-BM).

IV. Duration of response intracranially and extracranially. V. Progression-free survival. VI. Overall survival. VII. Immune modulation. VIII. Changes in circulating cell free deoxyribonucleic acid (cfDNA) as determinants of response and markers of early progression.

IX. Changes in relative apparent diffusion coefficient as measured by MRI as early predictor of response.

X. Changes in neurocognitive function and health-related quality of life. XI. Molecular and immunological changes demonstrated in extracranial lesions.

OUTLINE: Patients are assigned to 1 of 2 arms.

ARM I: Patients receive atezolizumab intravenously (IV) over 30-60 minutes and bevacizumab IV over 30-90 minutes on day 1. Cycles repeat every 14 days in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive atezolizumab IV over 30-60 minutes and bevacizumab IV over 30-90 minutes on day 1. Cycles with atezolizumab and bevacizumab repeat every 14 days in the absence of disease progression or unacceptable toxicity. Patients also receive cobimetinib orally (PO) thrice daily (TID) on days 1-21. Cycles with cobimetinib repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 90 days and then every 3 months thereafter.

Bevacizumab and Atezolizumab With or Without Cobimetinib in Treating Patients With Untreated Melanoma Brain Metastases

Phase II Study of BEvacizumab (Avastin) in Combination With Atezolizumab or Atezolizumab (Tencentriq) and Cobimetinib (Cotellic) in Patients With Untreated Melanoma Brain Metastases (TACo-BEAT-MBM)

Each response rate measure will be summarized using frequencies and percentages overall and by cohort. In addition, 90% exact confidence intervals will be presented for each response rate measure, for all patients and by cohort.

Safety assessments will consist of monitoring and reporting adverse events (AEs) and serious adverse events (SAEs) that are considered related to atezolizumab. Bevacizumab and cobimetinib, all events of death, and any study-specific issue of concern summaries of AEs and SAEs with respect to incidence, severity, and causality will be provided for all patients and by cohort. In addition, discontinuation due to AEs, SAEs and deaths will be summarized. Patients will also be evaluated for dose-limiting toxicities through the first cycle.

The safety and tolerability of the combination of atezolizumab, bevacizumab, cobimetinib in patients with BRAFV600 wild-type metastatic melanoma to the brain who've experienced prior progression on anti-PD1 will be assessed.

Each response rate measure will be summarized using frequencies and percentages overall and by cohort. In addition, 90% exact confidence intervals will be presented for each response rate measure, for all patients and by cohort. Associations between response and clinical measures of interest (e.g., changes in circulating cell free deoxyribonucleic acid \[cfDNA\]) will be determined by logistic regression models.

Duration of response is defined as the duration of time from date of first response to date of disease progression. DOR will be assessed using the Kaplan-Meier method overall and by cohort.

PFS is defined as the duration from treatment start date to date of disease progression or death. PFS will be assessed using the Kaplan-Meier method overall and by cohort.

Overall survival is defined as the time from treatment start date to death. OS will be assessed using the Kaplan-Meier method overall and by cohort.

National Cancer Institute (NCI)

M.D. Anderson Cancer Center

Spots Global Cancer Trial Database for intracranial melanoma