Novartis announces NEJM publication of pivotal study of Tabrecta(TM) in patients with METex14 metastatic non-small cell lung cancer

  • Tabrecta(TM) (capmatinib, formerly INC280) is the first and only therapy approved by the FDA to specifically target metastatic non-small cell lung cancer (NSCLC) with a mutation that leads to MET exon 14 skipping (METex14)
  • METex14 is an important biomarker for physicians to consider when selecting metastatic NSCLC treatment options1
  • In the US, METex14 metastatic NSCLC is diagnosed in ~4,000-5,000 patients annually and typically indicates aggressive disease with a poor prognosis2-3

Basel, September 2, 2020 - Data from the pivotal GEOMETRY mono-1 Phase II study published today in The New England Journal of Medicine (NEJM) show treatment with Tabrecta(TM) (capmatinib, formerly INC280) resulted in positive overall response rates (ORR) among adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have a mutation that leads to skipping of MET exon 14 (METex14)1. Positive duration of response (DOR) was also observed1. The presence of METex14 is a viable selection strategy for metastatic lung cancer patients who may be eligible for Tabrecta, thereby underscoring the importance of broad molecular testing for NSCLC patients1.

MET, a receptor tyrosine kinase coded by the MET gene, normally plays an important role in cell signaling, proliferation, and survival4. Many cancers are associated with abnormal signaling through the MET receptor pathway, caused by multiple mechanisms including point mutations, insertions/deletions that lead to skipping of exon 144. Until recently, one obstacle to effectively targeting MET has been the identification of an optimal biomarker, however, METex14 has emerged as a predictive biomarker for MET-directed therapies, such as Tabrecta1.

"The pivotal data published today not only confirm the positive results we’ve seen previously with Tabrecta treatment in non-small cell lung cancer, but  also underscore the value of early and broad molecular testing of patients’ tumors to guide treatment decisions for both first-line and previously treated patients, " said Jeff Legos, Senior Vice President, Head of Oncology Drug Development, Novartis Oncology. "We know patients with this particularly aggressive form of lung cancer have a poor prognosis; they are often older and more medically fragile. We are committed to continuing to work with global health authorities to bring Tabrecta to patients as quickly as possible."

Data in the study published today include the following confirmed ORRs by the Blinded Independent Radiology Committee (BIRC) to Tabrecta in the population with MET exon 14 skipping (n=97):

  • 68% ORR (95% CI, 48-84) among treatment-naive patients (n=28)1
  • 41% ORR (95% CI, 29-53) among previously treated patients (n=69)1

In patients with METex14 who responded to treatment with Tabrecta, the study also demonstrated:

  • Median duration of response of 12.6 months (95% CI, 5.6-not estimable) in treatment-naive patients (19 responders) and 9.7 months (95% CI, 5.6-13.0) in previously treated patients (28 responders)1

Thirteen of 14 patients with METex14 had brain metastases at baseline (3 treatment-naive and 10 previously treated patients) and were considered evaluable by the BIRC1. In a post-hoc analysis, 7 intracranial responses were observed, including 4 complete responses1.

The study adds to the scientific consensus that METex14 is an oncogenic driver1.
The most frequently reported treatment-related adverse events (incidence =20%) were peripheral edema (43%), nausea (34%), increased blood creatinine (18%), and vomiting (19%). The majority of the AEs were grades 1 or 21.

NSCLC accounts for approximately 85% of the 2 million new lung cancer diagnoses each year worldwide, including about 228,000 in the United States5-6. Nearly 70% of NSCLC patients have a genomic mutation7. METex14, a recognized oncogenic driver, occurs in approximately 3-4% of newly diagnosed advanced NSCLC cases (about 4,000 - 5,000 patients in the US annually)2,4,8-9.

Tabrecta (capmatinib) is a kinase inhibitor that targets MET. Tabrecta is licensed to Novartis by Incyte Corporation in 2009. Under the Agreement, Incyte granted Novartis worldwide exclusive development and commercialization rights to capmatinib and certain back-up compounds in all indications.

TABRECTA(TM) (capmatinib) tablets is a prescription medicine used to treat adults with a kind of lung cancer called non-small cell lung cancer (NSCLC) that has spread to other parts of the body or cannot be removed by surgery (metastatic), and whose tumors have an abnormal mesenchymal-epithelial transition (MET) gene.

The effectiveness of TABRECTA in these patients is based on a study that measured 2 types of response to treatment (response rate and duration of response). There is no clinical information available to show if patients treated with TABRECTA live longer or if their symptoms improve. There are ongoing studies to find out how TABRECTA works over a longer period of time.

It is not known if TABRECTA is safe and effective in children.