A Study to Compare the Administration of Encorafenib + Binimetinib + Nivolumab Versus Ipilimumab + Nivolumab in BRAF-V600 Mutant Melanoma With Brain Metastases
This phase II trial compares the effect of encorafenib, binimetinib, and nivolumab versus ipilimumab and nivolumab in treating patients with BRAF- V600 mutant melanoma that has spread to the brain (brain metastases). Encorafenib and binimetinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Ipilimumab and nivolumab are monoclonal antibodies that may interfere with the ability of tumor cells to grow and spread. This trial aims to find out which approach is more effective in shrinking and controlling brain metastases from melanoma.
Eligibility criteria
This trial does not accept healthy volunteers
Qualifiers
Participants must have histologically and pathologically confirmed melanoma that has metastasized to the brain
Any primary (cutaneous, acral/mucosal, etc) or unknown origin are permitted, except that participants with uveal primary are not eligible
Participants must have BRAF-V600 mutant melanoma documented by a Clinical Laboratory Improvement Act (CLIA)-certified laboratory
All participants must have an magnetic resonance imaging (MRI) of the brain within 28 days prior to registration and must have central nervous system metastases with at least one measurable brain metastasis >= 0.5 cm in size (per modified RECIST 1.1) that has not been irradiated, or progressed (in the opinion of the treating physician) after prior radiation therapy. Participating sites MUST use MRI slice thickness of =< 1.5 mm and are recommended to adhere to the 'minimum' Brain Tumor Imaging Protocol for Clinical Trials in Brain Metastases (BTIP-BM) compliant MRI acquisition protocol. Computed tomography (CT) of the head cannot substitute for brain MRI. (NOTE: All central nervous system [CNS] disease must be documented on BOTH the Brain Metastases Baseline Tumor Assessment Form, using modified RECIST, and the Baseline Tumor Assessment Form [RECIST 1.1] using RECIST 1.1.)
Disqualifiers
Participants must not have received prior systemic therapy for metastatic disease. Prior systemic therapy received only in the neoadjuvant and/or adjuvant setting (e.g., BRAF/MEK inhibitor therapy, anti-PD-1 therapy or anti-CTLA4 therapy, alfa-interferon, etc.) is permitted. If patients received prior neoadjuvant/adjuvant therapy, they must have had eventual disease relapse prior to randomization
Participants must not have had prior radiation therapy within 7 days prior to randomization
Participants must not be planning to require any additional form of systemic anti-tumor therapy for melanoma while on protocol treatment
Participants must not be planning to use hormonal contraceptives
Trial design
Design model
Parallel
Treatments tested in this trial
Binimetinib
Drug
Given PO
Encorafenib
Drug
Given PO
Ipilimumab
Biological/Vaccine
Given IV
Nivolumab
Biological/Vaccine
Given IV
Treatment groups
112 Participants
are divided into 2 treatment groups
Group A: Arm I (encorafenib, binimetinib, nivolumab)Experimental treatment 3 interventions
Group B: Arm II (nivolumab, ipilimumab)Experimental treatment 2 interventions
Trial outcomes
Primary outcomes
1
Progression-free survival
Will be assessed by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
Time frame
From date of registration to date of first documentation of progression, or symptomatic deterioration, or death due to any cause, assessed up to 3 years after randomization
Secondary outcomes
1
Overall survival (OS)
Will be assessed by Immunotherapy Response Assessment Criteria for Intracranial Metastases (RANO-BM). Will construct Kaplan-Meier plots and estimate the median OS and construct 95% Brookmeyer-Crowley Confidence intervals.
Time frame
From date of registration to date of death due to any cause, assessed up to 3 years after randomization
2
Intracranial response rate (ICRR)
The ICRR is defined as the best response when applying modified (m)RECIST criteria. Will compare intracranial response based on assessments per mRECIST, RANO-BM and immunotherapy (i)RANO criteria based on a review of the banked images. For each of these methods, the best response to treatment will be summarized by treatment arm, the percent agreement between each pair of methods will be reported along with a 95% confidence interval, and a p-value based on a two-sided McNemar's test will be calculated.
Time frame
Up to 3 years after randomization
3
Objective response rate
Will be assessed by RECIST 1.1.
Time frame
Up to 3 years after randomization
4
Duration of response
Time frame
Up to 3 years after randomization
Other outcomes
Sponsors and contacts
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