On April 22, 2022 Incyte (Nasdaq:INCY) reported that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency’s (EMA) has issued a positive opinion that recommends granting marketing authorization for capmatinib (Tabrecta) as a monotherapy for the treatment of adults with advanced non-small cell lung cancer (NSCLC) harboring alterations leading to mesenchymalepithelial-transition factor gene (MET) exon 14 (METex14) skipping who require systemic therapy following prior treatment with immunotherapy and/or platinum-based chemotherapy (Press release, Incyte, APR 22, 2022, View Source [SID1234612836]).

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"We are pleased by the positive CHMP opinion recommending capmatinib as a treatment for certain patients with METex14 advanced non-small cell lung cancer and encouraged by what this Incyte-discovered product could mean for patients in Europe," said Peter Langmuir, M.D., Group Vice President, Oncology Targeted Therapies, Incyte. "Now patients in Europe who have advanced NSCLC with alterations leading to METex14 skipping are closer to having another therapeutic option that may target the recognized oncogenic driver of their cancer."

The CHMP opinion is based on data the Phase 2 GEOMETRY mono-1 study that demonstrated positive overall response rates (ORR) among adult patients with advanced NSCLC whose tumors have alterations leading to METex14 skipping1. Based on data presented at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, in the 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.

"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 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."

In the European Union, there are an estimated 291,000 patients with locally advanced or metastatic NSCLC4. METex14 skipping, a recognized oncogenic driver2, occurs in approximately 3-4% of NSCLC cases3.

Novartis has exclusive worldwide development and commercialization rights to Tabrecta. Incyte is eligible for a total of over $500 million in milestones as well as royalties of between 12-14% on global net sales by Novartis.

About GEOMETRY mono-1
The Novartis-sponsored GEOMETRY mono-1 trial is a Phase 2, 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 Tabrecta (capmatinib)
Tabrecta is approved in several countries including the U.S., Japan and Switzerland. It is the number one prescribed targeted therapy for patients with advanced NSCLC with alterations leading to METex14 skipping globally5.

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 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 survival2. 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 pathway2.

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.