EAY191-A6 ComboMATCH Treatment Trial: FOLFOX in Combination with Binimetinib as 2nd Line Therapy for Patients with Advanced Biliary Tract Cancers with MAPK Pathway Alterations

This phase II ComboMATCH treatment trial compares the usual treatment of modified leucovorin, fluorouracil and oxaliplatin (mFOLFOX6) chemotherapy to using binimetinib plus mFOLFOX6 chemotherapy to shrink tumors in patients with biliary tract cancers that have spread to other places in the body (advanced) and had progression of cancer after previous treatments (2nd line setting). Fluorouracil is in a class of medications called antimetabolites. It works by slowing or stopping the growth of cancer cells in the body. Oxaliplatin is in a class of medications called platinum-containing antineoplastic agents. It works by killing tumor cells. Leucovorin may help the other drugs in the mFOLFOX6 chemotherapy regimen work better by making tumor cells more sensitive to the drugs. Binimetinib is in a class of medications called kinase inhibitors. It works by blocking the action of the abnormal protein that signals tumor cells to multiply. This helps to stop or slow the spread of tumor cells. Giving binimetinib in combination with mFOLFOX6 chemotherapy may be effective in shrinking or stabilizing advanced biliary tract cancers in the 2nd line setting.

This study has public funding from the National Cancer Institute (NCI), part of the National Institutes of Health (NIH) in the United States Department of Health and Human Services.

Inova Schar Cancer Institute
A division of Inova Fairfax Hospital
8081 Innovation Park Drive 
Fairfax, VA 22031

• Patient must have enrolled onto EAY191 and must have been given a treatment assignment to ComboMATCH to EAY191-A6 based on the presence of an actionable mutation as defined in EAY191
• Patients must be registered to the ComboMATCH Registration Protocol (EAY191)
• Patients must have RAS/RAF/MEK/ERK mutations as determined by the ComboMATCH screening assessment
• Patients must have disease that can be safely biopsied and agree to a pre-treatment biopsy or have archival tissue available from within 12 months prior to registration
• Please note the current actionable marker of interest (aMOI)/actionable alteration list for this treatment trial can be found on the Cancer Trials Support Unit (CTSU) website: www.ctsu.org (final uniform resource locator [URL] pending).
  Please note novel/Dynamic aMOI can be submitted for review per the process described in the ComboMATCH Registration Protocol
• Participants must have histologically confirmed BTC (intrahepatic cholangiocarcinoma [IHC], extrahepatic cholangiocarcinoma [EHC] or gallbladder cancer [GBC]) that is unresectable or recurrent with a confirmed RAS/RAF/MEK/ERK pathway mutation via any Clinical Laboratory Improvement Act (CLIA)-certified method. BRAFV600E mutations are not eligible due to other ongoing/upcoming studies in this disease cohort
  Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 Of note, in the case when a baseline biopsy is done after scans are obtained, a lesion separate from one that is biopsied needs to be measurable per RECIST 1.1. All radiologic studies must be performed within 28 days prior to randomization

Each ComboMATCH Treatment Trial contains specific eligibility criteria. If patient is found to not be eligible for the assigned ComboMATCH Treatment Trial, indication of ineligibility will trigger re-evaluation and potential assignment to another Treatment Trial

For more information, visit:

https://clinicaltrials.gov/study/NCT05564403?term=EAY191-A6&rank=2#participation-criteria