A Study to Evaluate the Safety and Activity of Belvarafenib as a Single Agent and in Combination With Either Cobimetinib or Cobimetinib Plus Nivolumab in Patients With NRAS-mutant Advanced Melanoma.
NCT ID: NCT04835805
Last Updated: 2025-12-31
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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ACTIVE_NOT_RECRUITING
PHASE1
65 participants
INTERVENTIONAL
2021-05-13
2025-12-31
Brief Summary
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Detailed Description
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Conditions
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Study Design
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NON_RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Belvarafenib Monotherapy
Twice daily (BID), continuous dosing.
Belvarafenib
Twice daily (BID), continuous dosing
Belvarafenib Plus Cobimetinib
Recommended dose (RD) and schedule of belvarafenib and cobimetinib selected based on the safety data, tolerability, pharmacokinetics, and anti-tumor activity tested in dose-finding phase followed by an expansion phase.
Cobimetinib
Once daily (QD) or three times weekly (TIW) for 21 days, 7 days off
Belvarafenib Plus Cobimetinib Plus Nivolumab
Recommended dose (RD) and schedule of belvarafenib and cobimetinib plus nivolumab IV infusion every 4 weeks (Q4W) in a run-in phase followed by an expansion phase
Nivolumab
Once every 4 weeks (Q4W)
Interventions
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Belvarafenib
Twice daily (BID), continuous dosing
Cobimetinib
Once daily (QD) or three times weekly (TIW) for 21 days, 7 days off
Nivolumab
Once every 4 weeks (Q4W)
Eligibility Criteria
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Inclusion Criteria
* Histologically confirmed, metastatic (recurrent or de novo Stage IV) or unresectable locally advanced (Stage III) cutaneous melanoma, that has progressed on or after treatment with anti-PD-1 or anti-PD-L1 therapy. Patients may have received up to two lines of systemic cancer therapy. Treatment with anti-PD-1/PD-L1 in the adjuvant setting is acceptable. Patients must have progressed disease at study entry
* Documentation of NRAS mutation-positive within 5 years prior to screening
* Tumor specimen availability
* Adequate hematologic and end-organ function
* Measurable disease per RECIST v1.1
Exclusion Criteria
* Treatment with systemic immunotherapy agents (e.g., anti-CTLA4, anti-PD(L)1, cytokine therapy, investigational therapy, etc.) within 28 days prior to C1D1
* Symptomatic, untreated, or actively progressing CNS metastases
* History or signs/symptoms of clinically significant cardiovascular disease
* Known clinically significant liver disease
* History of autoimmune disease or immune deficiency
* Prior treatment with a MEK inhibitor (cobimetinib arm)
* History of or evidence of retinal pathology on ophthalmologic examination (cobimetinib arm)
* History of immune-related AE attributed to prior anti-PD(L)1 therapy that resulted in permanent discontinuation of anti-PD(L)1 therapy (nivolumab arm)
18 Years
ALL
No
Sponsors
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Genentech, Inc.
INDUSTRY
Responsible Party
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Principal Investigators
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Clinical Trials
Role: STUDY_DIRECTOR
Hoffmann-La Roche
Locations
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California Pacific Medical Center Research Institute
San Francisco, California, United States
UCSF Helen Diller Family CCC
San Francisco, California, United States
University of Colorado Cancer Center
Aurora, Colorado, United States
Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
Baltimore, Maryland, United States
Washington University School of Medicine
St Louis, Missouri, United States
Memorial Sloan Kettering
New York, New York, United States
Calvary Mater Newcastle
Waratah, New South Wales, Australia
Peter MacCallum Cancer Centre-East Melbourne
Melbourne, Victoria, Australia
Linear Clinical Research Ltd
Nedlands, Western Australia, Australia
Ottawa Hospital Regional Cancer Centre
Ottawa, Ontario, Canada
Princess Margaret Hospital
Toronto, Ontario, Canada
Charité - Universitätsmedizin Berlin
Berlin, , Germany
Universitätsklinikum Hamburg-Eppendorf
Hamburg, , Germany
Klinikum Mannheim GmbH Universitätsklinikum
Mannheim, , Germany
Universitatsklinikum Tubingen
Tübingen, , Germany
Universitätsklinikum Würzburg
Würzburg, , Germany
Asan Medical Center - PPDS
Seoul, , South Korea
Countries
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References
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Moschos SJ. War against NRAS-Mutant Melanoma Using Targeted Therapies Remains Challenging. Clin Cancer Res. 2022 Jul 15;28(14):2977-2979. doi: 10.1158/1078-0432.CCR-22-1256.
Other Identifiers
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2020-003674-41
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
GO42273
Identifier Type: -
Identifier Source: org_study_id