Novartis Gets FDA Approval for Targeted Drug Tabrecta for NSCLC

Novartis Gets FDA Approval for Targeted Drug Tabrecta for NSCLC

The FDA has given approval to Novartis Pharmaceutical’s targeted therapeutic Tabrecta for the treatment of metastatic NSCLC.

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, accounting for up to 90 percent of all lung carcinomas. It is an aggressive cancer that begins in epithelial cells lining the lungs with a high likelihood of metastasizing to other parts of the body. Current treatments include chemotherapy and radiation, with the increasing inclusion and development of new targeted therapies against specific gene mutations.

The US Food and Drug Administration (FDA) has now granted approval to the targeted therapeutic Tabrecta (capmatinib) for the treatment of MetEx14 metastatic NSCLC based on positive clinical trials results in patients.

Tabrecta is an oral MET inhibitor that has been approved for adult patients with metastatic NSCLC whose tumor cells harbor the MetEx14 mutation that leads to skipping of exon 14 in the MET gene during transcription. This mutation leads to abnormal activation of the MET tyrosine kinase, which leads to enhanced tumor growth and metastasis.

Tabrecta was given approval to Novartis Pharmaceuticals Inc. through the Accelerated Approval pathway, which gives approvals for drugs in the “treatment of serious or life-threatening diseases that provide a meaningful advantage over existing treatments,” according to the FDA.

Alongside the targeted therapy, the FDA has also given Foundation Medicine, Inc. approval for its FoundationOne CDx assay (F1CDx), which is a diagnostic test specified for the detection of MetEx14.

The approval was based on preliminary results from the GEOMETRY mono-1 Phase II multi-center, a non-randomized, open-label, multi-cohort study that evaluated the efficacy of Tabrecta in MetEx14 NSCLC patients.

Related: Liquid Biopsies Help Match Cancer Patients to Phase I Trials

In a press release by the FDA, Dr. Richard Pazdur, Director of the FDA’s Oncology Center of Excellence and acting Director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research stated that, “Lung cancer is increasingly being divided into multiple subsets of molecularly defined populations with drugs being developed to target these specific groups.”

Dr. Pazdur added that, “Tabrecta is the first approval specifically for the treatment of patients with non-small cell lung cancer whose tumors have mutations that lead to MET exon 14 skipping. This patient population now has an option for a targeted therapy, which they didn’t have prior to today.”

Aberrant MET activation in cancers is associated with poor prognosis as it leads to stimulation of tumor growth, angiogenesis (formation of new blood vessels that supply the tumor) and metastasis. MET is deregulated in many human cancers including cancers of the kidney, liver, stomach, breast, lung and brain.

Somatic mutations in the MET gene have been identified as common driver mutations in lung cancers. Of these mutations, MetEx14 is found in three to four percent of all lung cancer cases. Skipping of MET exon 14 leads to a cellular epithelial-mesenchymal transition (EMT), which is a critical step in the metastasis of cancers.

MetEx14 has been shown to be a predictive biomarker for crizotinib treatment, another approved targeted treatment for NSCLC in patients that have mutations in the anaplastic lymphoma kinase (ALK) or the related ROS1 kinase.

The GEOMETRY trial for Tabrecta involved MetEx14 NSCLC patients with molecular characteristics including wild-type or negative status for epidermal growth factor receptor (EGFR) and ALK, in addition to at least one measurable lesion.

In the trial, patients received Tabrecta 400 mg orally twice daily until disease progression or unacceptable toxicity. The main outcome measure for efficacy was overall response rate (ORR), which was indicated by tumor shrinkage in patients.

The study found that the ORR for 28 patients who received Tabrecta and did not receive any prior treatment for NSCLC was 68 percent, while the ORR was found to be 41 percent for 69 patients who were previously treated. Patients that had received previous treatment all had a partial response to Tabrecta while untreated patients had a mix of complete and partial responses.

In addition, of responding patients who had not undergone treatment for NSCLC, 47 percent had a response duration lasting 12 months or longer compared to 32.1 percent of responding participants who had been previously treated.

The FDA granted the drug application “Breakthrough Therapy” designation, which expedites the development and review of drugs that are intended to treat a serious condition, when “preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over available therapies, and Priority Review designation,” according to the FDA’s press release.

Moreover, Tabrecta received Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases.