Xiuning Le, MD, Ph.D., Department of Thoracic-Head and Neck Med Onc, Division of Cancer Medicine MD Anderson speaks about Tepotinib Phase II in NSCLC Harboring MET Alterations (VISION).
Link to the Trial:
https://clinicaltrials.gov/ct2/show/NCT02864992
Brief Synopsis:
The VISION Study is a phase two, single-arm, multi-center, global trial that evaluated the efficacy of tepotinib, a small molecule inhibitor targeting MET, in patients with non-small cell lung cancer (NSCLC) exhibiting MET exon 14 skipping alterations. This trial allowed enrollment of patients identified with MET exon 14 alterations in their lung cancer, detected either through tissue biopsy or circulating tumor DNA (ctDNA) via liquid biopsy, offering flexibility in patient inclusion criteria.
Patients began treatment with tepotinib, and their response to the medication was evaluated systematically. The outcomes of this study, published in the New England Journal of Medicine last year, demonstrated significant patient benefits from tepotinib treatment. Approximately 44% of patients experienced an objective response, indicating a substantial tumor reduction from baseline, with the durability of response ranging between 8 to 12 months. These results underscored tepotinib’s potential as a highly selective and potent oral medication for NSCLC patients with MET exon 14 skipping alterations.
Encouragingly, the U.S. Food and Drug Administration (FDA) approved tepotinib for clinical use in February 2021 for patients with MET exon 14 skipping NSCLC, enabling oncologists nationwide to prescribe this targeted therapy. This approval has significantly impacted treatment paradigms, offering new strategies for patient care and enhancing the therapeutic arsenal available to oncologists.
Common inquiries about tepotinib revolve around its toxicity profile and the optimal sequence of its use in treatment plans. The drug is generally well-tolerated, with peripheral edema being the most common side effect, managed through lifestyle adjustments and possibly dose modifications rather than medical interventions. As for treatment sequencing, the emphasis is on offering targeted therapy early in the treatment process, especially considering the median age of patients and the promising response rates. However, the integration of chemotherapy and immunotherapy remains vital, ensuring a comprehensive approach to treatment.
The ongoing exploration in the field aims to enhance clinical benefits further, investigating translational and clinical research avenues to achieve higher response rates and longer progression-free survival. Additionally, the potential of Topatinib and other tyrosine kinase inhibitors (TKIs) in earlier-stage patients and in conjunction with surgical interventions is under investigation, promising to refine treatment strategies further.
The broader landscape of NSCLC treatment is evolving, with 2020 marking the approval of several highly selective TKIs, including those targeting RED alterations, and spotlighting actionable mutations like KRAS and ERBB2 as emerging targets for novel therapies. This progress emphasizes the critical role of genetic testing in identifying eligible patients for targeted treatments, underscoring a collective effort to expand the knowledge base and improve patient outcomes in lung cancer treatment.
The aim of this research is to see how successful the study drug (tepotinib) is at slowing the progression of lung cancer. This research would also assess the study drug’s efficacy and side effects, as well as how the study drug is processed by the body and how the study drug impacts the quality of life. A pharmacogenetic testing component is also available as an add-on to the analysis. Since changes in genes will affect how an individual reacts to a specific medication, pharmacogenetic analysis is an essential way and try to understand the importance of genetics in human disease and how genes influence drug efficacy.
Ages Eligible to Participate in Research:
18 years old and up (Adult, Older Adult)
The sexes Study Eligibility: Accepts all Volunteers who are in good health: There are no requirements.
Criteria for Acceptance:
Prior to any trial-specific screening process, the subject or legal guardian must sign a written informed consent form.
Male or female, 18 years of age or older (or have passed the age of majority according to local laws and regulations)
An independent review committee (IRC) reported measurable disease in compliance with RECIST version 1.1 Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1
If a female respondent is not pregnant or breastfeeding, and at least one of the following provisions holds, she is entitled to apply.
OR you are not a woman who is capable of bearing children.
a woman of childbearing age who agrees to use an extremely successful form of contraception
A male participant must commit to use and make their female partners with childbearing potential use a highly efficient contraceptive method.
NSCLC that has been verified histologically or cytologically as advanced (locally advanced or metastatic) (all types including squamous and sarcomatoid)
Pretreated patients with no more than two lines of previous care or treatment-naive patients in first-line
Subjects with METex14 skipping alterations in plasma and/or tissue, as determined by the central laboratory or an assay with sufficient regulatory status
Criteria for exclusion:
Subjects with known activating mutations in the Epidermal Growth Factor Receptor (EGFR) that predict susceptibility to anti-EGFR therapy
Anaplastic Lymphoma Kinase (ALK) rearrangements that are known to predict susceptibility to anti-ALK therapy
Neurologically dysfunctional patients with symptomatic brain metastases
Any unresolved toxicity Grade 2 or higher from prior anticancer treatment, as defined by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE).
Transfusion needed within 14 days of the first dose of trial therapy
Prior to the first dose of trial treatment, you would have received chemotherapy, biological therapy, radiation therapy, hormone therapy for anti-cancer reasons, targeted therapy, or other investigational anticancer therapy (excluding palliative radiotherapy at focal sites) within the previous 21 days.
Brain metastasis is the only detectable lesion in the subjects.
Hematological, lung, kidney, and heart activity are also impaired.
Other agents that target the Hepatocyte Growth Factor c(HGF/c) were used previously. – Meteorological route
Normal medications have failed to control hypertension (it has not been regulated at 150/90 mmHg).
Other than curatively cured non-melanoma skin cancer, in situ carcinoma of the cervix, or other cancer curatively treated and with no signs of disease for at least 5 years, past or present history of neoplasms other than Non-small Cell Lung Cancer (NSCLC).
Medical history of trouble chewing, malabsorption, or other chronic gastrointestinal disorder, or other disorders that may impair test product enforcement and/or absorption
Known infection with human immunodeficiency virus, or active infection with hepatitis B or hepatitis C virus within 28 days of the start of the trial treatment
In the discretion of the investigators, substance misuse, active infection, or any acute or chronic medical or psychological disorder or laboratory anomalies can raise the risk associated with trial attendance.
Hypersensitivity to some of the substances in the trial procedure
Small legal capability or legal incapacity
Any other explanation that, in the view of the Principal Investigator, prevents the subject from taking part in the study
In the last 30 days, you’ve taken part in another clinical trial.