Binimetinib and Encorafenib for the Treatment of Advanced Solid Tumours With Non-V600E BRAF Mutations

Official Title

Binimetinib and Encorafenib for the Treatment of Advanced Solid Tumours With Non-V600E BRAF Mutations

Summary:

This is a single-centre, open-label Phase II study of the investigational drugs binimetinib and encorafenib that will be taken my mouth (orally) daily in adult patient with advanced and/or metastatic solid tumours for which no other standard therapy is available. The main purpose is to evaluate the objective response rate (ORR) of the study drugs in the growth of the cancer in patients with class 2 and 3 BRAF mutations.

Trial Description

Primary Outcome:

  • Objective response rate defined as per RECIST v1.1.
Secondary Outcome:
  • Number of participants with toxicities as per NCI CTCAE v5.0.
  • Disease progression defined as per RECIST v1.1 and monitored throughout the study period. Progression Free Survival defined as time from study registration to disease progression or death from any cause.
  • Disease Control Rate defined in accordance with RECIST v1.1, as the percentage of patients who achieve a complete response, partial response or stable disease after 24 weeks of treatment.
  • Overall survival measured as the length of time from the first day of treatment to the day of death. Median OS will be reported.
  • Change in circulating tumour DNA (ctDNA) profiles measured by serial analysis of ctDNA profiles at baseline, mid-cycle 1, with each subsequent cycle, and at progression, validated by comparison to molecular profiles of corresponding fresh tumour biopsies
  • Number of fresh tumour biopsies collected, frozen, and stored for subsequent development of patient derived xenografts.
  • Number of identified molecular mechanisms of acquired resistance to binimetinib and encorafenib in tumours with non-V600E BRAF mutations, measured by analysis of molecular profiles and validated with PDX models in vitro and in vivo.
BRAF is a gene in humans that is commonly altered in cancer, resulting in a change to the proteins created from this mutation. These altered proteins interact with a process in the body known as the MAPK (mitogen-activated protein kinase) pathway and promote the growth of cancer. Three classes of BRAF mutations have been identified to understand why some patients respond to treatment and others do not. Class 2 and 3 BRAF mutations have worse overall survival. This study will look at participants in these classes (non-V600E BRAF mutations). Binimetinib is an oral drug (tablet) that stops the function of MEK (mitogen-activated protein kinase kinase). MEK is a part of the MAPK pathway, so blocking this step helps in stopping the pathway from confinuing to grow the cancer. Encorafenib is an oral drug (capsule) that stops the function of BRAF V600-mutant kinase, the protein that is produced from a type of BRAF gene mutation. This protein promotes the MAPK pathway so blocking this protein stops the MAPK pathway from growing the cancer. Patients will visit the clinic up to 2 times every 4 weeks (1 cycle) for tests and procedures while taking the study drugs daily. Procedures will involve review of medication and history, imaging scans, blood sample collection for safety and research purposes, urine collection, ECGs, eye exam, MUGA scans and mandatory and optional tumour biopsies.

View this trial on ClinicalTrials.gov

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Resources

Canadian Cancer Society

These resources are provided in partnership with the Canadian Cancer Society