Randomized Phase II Trial of Encorafenib and Cetuximab With or Without Nivolumab (NSC #748726) for Patients With Previously Treated, Microsatellite Stable, BRAFV600E Metastatic and/or Unresectable Colorectal Cancer
This phase II trial tests whether adding nivolumab to the usual treatment (encorafenib and
cetuximab) works better than the usual treatment alone to shrink tumors in patients with
colorectal cancer that has spread to other places in the body (metastatic) or that cannot be
removed by surgery (unresectable) and whose tumor has a mutation in a gene called BRAF.
Encorafenib is in a class of medications called kinase inhibitors. It is used in patients
whose cancer has a certain mutation (change) in the BRAF gene. It works by blocking the
action of mutated BRAF that signals cancer cells to multiply. This helps to stop or slow the
spread of cancer cells. Cetuximab is in a class of medications called monoclonal antibodies.
It binds to a protein called EGFR, which is found on some types of cancer cells. This may
help keep cancer cells from growing. Immunotherapy with monoclonal antibodies, such as
nivolumab, may help the body's immune system attack the cancer, and may interfere with the
ability of tumor cells to grow and spread. Giving nivolumab in combination with encorafenib
and cetuximab may be more effective than encorafenib and cetuximab alone at stopping tumor
growth and spreading in patients with metastatic or unresectable BRAF-mutant colorectal
I. To compare progression-free survival (PFS) per Response Evaluation Criteria in Solid
Tumors (RECIST) 1.1 in patients with microsatellite stable (MSS), BRAF^V600E metastatic
and/or unresectable colorectal cancer (CRC) randomized to treatment with nivolumab +
encorafenib + cetuximab compared to encorafenib + cetuximab.
I. To compare overall response rate (ORR), including confirmed and unconfirmed, complete and
partial response, according to RECIST 1.1 criteria between the two arms.
II. To compare overall survival (OS) between the two arms. III. To compare duration of
response between the two arms. IV. To compare safety and tolerability between the two arms.
V. To assess immune-related PFS using modified response criteria adapted for immunotherapy
(irRC-PFS) in patients treated with nivolumab + encorafenib + cetuximab.
I. To bank tissue and blood specimens for future correlative studies.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I: Patients receive encorafenib orally (PO) once daily (QD) on days 1-28, cetuximab
intravenously (IV) on days 1 and 15, and nivolumab IV on day 1. Cycles repeat every 28 days
in the absence of disease progression or unacceptable toxicity.
ARM II: Patients receive encorafenib PO QD on days 1-28 and cetuximab IV on days 1 and 15.
Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed until death or 3 years after
registration, whichever occurs first.
Metastatic Colon Adenocarcinoma, Metastatic Rectal Adenocarcinoma, Stage III Colon Cancer AJCC v8, Stage III Rectal Cancer AJCC v8, Stage IV Colon Cancer AJCC v8, Stage IV Rectal Cancer AJCC v8, Unresectable Colon Adenocarcinoma, Unresectable Rectal Adenocarcinoma
If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.
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