On April 22, 2022 Novartis reported that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion and recommended granting marketing authorization of Tabrecta (capmatinib) as a monotherapy for the treatment of adults with advanced non-small cell lung cancer (NSCLC) harboring alterations leading to mesenchymal-epithelial-transition factor gene (MET) exon 14 (METex14) skipping who require systemic therapy following prior treatment with immunotherapy and/or platinum-based chemotherapy (Press release, Novartis, APR 22, 2022, View Source [SID1234612866]).
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"Patients with alterations leading to METex14 skipping have an urgent need for treatment options, as this form of lung cancer is aggressive, often diagnosed in an advanced stage and frequently comes with a poor prognosis," said Juergen Wolf, MD, from the Center for Integrated Oncology, University Hospital Cologne, Germany, and lead investigator of the GEOMETRY mono-1 trial. "The positive CHMP opinion for Tabrecta brings an option to patients for a treatment specific to their tumor. If approved by the European Commission, new targeted therapies like Tabrecta—supported by early and broad molecular testing of patients’ tumors—can better guide treatment decisions and ensure patients receive the appropriate therapy for their cancer."
The CHMP opinion is based on results from the Phase II GEOMETRY mono-1 trial that demonstrated positive overall response rates (ORR) among adult patients with advanced NSCLC whose tumors had alterations leading to METex14 skipping1. Based on data presented at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, among 31 patients who received Tabrecta as second-line therapy in the METex14 skipping pretreated population, a confirmed ORR of 51.6% (95% CI, 33.1-69.8) was achieved, and the ORR across all 100 previously-treated patients, which included patients who received one or two prior lines of systemic therapy, was 44.0% (95% CI, 34.1-54.3)1. The most common treatment-related adverse events (AEs) (incidence ≥20%)were peripheral oedema, nausea, fatigue, vomiting, dyspnea, decreased appetite and back pain1.
"Every 30 seconds, someone dies of lung cancer—the need for more treatment options is critical. Through research and targeted therapies like Tabrecta, we are working to change that statistic and make a positive impact on the lives of people affected by cancer around the world," said Marie-France Tschudin, President, Innovative Medicines International & Chief Commercial Officer, Novartis. "Today’s announcement represents an important step forward for people in the European Union with previously-treated advanced NSCLC having alterations leading to METex14 skipping."
In the European Union, there are an estimated 291,000 patients with locally advanced or metastatic NSCLC5. METex14 skipping, a recognized oncogenic driver, occurs in approximately 3-4% of NSCLC cases3,4.
About Tabrecta (capmatinib)
Tabrecta (capmatinib) is approved in several countries including the US, Switzerland and Japan. It is the number one prescribed targeted therapy for patients with advanced NSCLC with alterations leading to METex14 skipping globally2.
Tabrecta is a kinase inhibitor that targets MET. Tabrecta was discovered by Incyte and licensed to Novartis in 2009. Under the agreement, Incyte granted Novartis worldwide exclusive development and commercialization rights to capmatinib and certain back-up compounds in all indications.
About GEOMETRY mono-1
GEOMETRY mono-1 is a Phase II multi-center, non-randomized, open-label, multi-cohort study in adult patients with EGFR wild-type, ALK-negative rearrangement, advanced NSCLC with alterations that lead to MET exon-14 skipping who received 400 mg of capmatinib orally twice daily1.
Patients were assigned to cohorts on the basis of MET status and previous lines of therapy. The primary endpoint was overall response rate (ORR) based on the Blinded Independent Review Committee (BIRC) assessment per RECIST v1.1. The key secondary endpoint was duration of response (DOR) evaluated by BIRC1.
Mature data from the trial, including from an expansion cohort analysis, showed Tabrecta demonstrated a median duration of response of 9.7 months (95% CI, 5.6-13.0) in all previously-treated patients (n=100)1. In addition, Tabrecta demonstrated a median overall survival of 13.6 months (95% CI, 8.6-22.2) in previously-treated patients (n=69)1. The median progression-free survival was 5.5 months (95% CI, 4.2‑8.1) for all previously-treated patients (n=100) and 6.9 months (95% CI, 4.2-13.3) for patients who received Tabrecta as second-line therapy (n=31)1. The Disease Control Rate across all previously-treated patients was 82.0% (95% CI, 73.1-89.0)1. The expansion cohort analysis enrolled 160 patients with MET alterations and included previously-treated cohorts (n=100) who had been treated with one or two prior lines of systemic therapy for advanced disease, as well as treatment-naive cohorts (n=60)1.
Overall, Tabrecta demonstrated a manageable safety profile and there were no new safety signals or unexpected safety findings1. The most common treatment-related adverse events (AEs) (incidence ≥20%) were peripheral oedema, nausea, fatigue, vomiting, dyspnea, decreased appetite and back pain1.
About MET exon 14 skipping
MET (mesenchymal-epithelial transition), a receptor tyrosine kinase coded by the MET gene, normally plays an important role in cell signaling, proliferation and survival3. Many cancers are associated with abnormal signaling through the MET receptor pathway, caused by multiple mechanisms including point mutations, insertions and deletions that lead to skipping of exon 14. MET exon 14 (METex14) skipping is an oncogenic alteration in NSCLC that can result in overstimulation of the MET pathway3.
Patients with alterations that lead to METex14 skipping often have a poor prognosis due to the aggressiveness of the cancer and limited treatment options6-8.
Novartis and lung cancer
The needs in lung cancer are urgent and significant. Each year, more than 2 million people are newly diagnosed globally, and lung cancer remains the number one cause of cancer-related death worldwide9. There are two main types of lung cancer—small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). NSCLC accounts for approximately 85% of lung cancer diagnoses10.
Novartis is making bold investments in advancing the science to drive treatment and make an impact for patients around the world. The company is committed to working with the scientific and medical communities to reimagine the treatment of lung cancer and pursue advances in medicine that could extend the survival of people living with lung cancer.
With one of the most diverse lung cancer development programs in the industry, Novartis is developing therapies that block cancer growth; learning more about ways to activate the body’s immune system; increasing understanding of the relationship between unregulated inflammation and tumor growth and recurrence; and exploring the potential for advanced nuclear medicine to fight the disease. Through these programs, Novartis aims to redefine possibilities in lung cancer and pursue a trajectory to make lung cancer history.