FDA approves first targeted therapy to treat aggressive form of lung cancer

The US Food and Drug Administration (FDA) has approved Tabrecta (capmatinib) for the treatment of adult patients with non-small cell lung cancer (NSCLC) that has spread to other parts of the body. Tabrecta is the first FDA-approved therapy to treat NSCLC with specific mutations (those that lead to mesenchymal-epithelial transition or MET exon 14 skipping).

The FDA has also approved the FoundationOne CDx assay (F1CDx) as a companion diagnostic for Tabrecta. The F1CDx is a next-generation sequencing-based in vitro diagnostic device that is capable of detecting several mutations, including mutations that lead to MET exon 14 skipping.

“Lung cancer is increasingly being divided into multiple subsets of molecularly defined populations with drugs being developed to target these specific groups,” said Richard Pazdur, MD, Director – Oncology Center of Excellence, FDA, and Acting Director – Office of Oncologic Diseases, Center for Drug Evaluation and Research, FDA. “Tabrecta is the first approval specifically for the treatment of patients with non-small cell lung cancer whose tumours 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 earlier.”

NSCLC is a disease in which malignant cancer cells form in the tissues of the lung. It is the most common type of lung cancer with up to 90 per cent of all lung carcinomas falling into the non-small cell category. NSCLC occurs when healthy cells become abnormal and grow rapidly. One danger of this form of cancer is that there’s a high likelihood that the cancer cells will spread from the lungs to other organs and body parts. Cancer metastasis consists of a sequential series of events and MET exon 14 skipping is recognised as a critical event for metastasis of carcinomas. Mutations leading to MET exon 14 skipping are found in three to four per cent of patients with lung cancer.

Tabrecta is a kinase inhibitor, meaning it functions by blocking a key enzyme that results in helping to stop the tumour cells from growing. The FDA-approved Tabrecta based on the results of a clinical trial involving patients with NSCLC with mutations leads to MET exon 14 skipping, epidermal growth factor receptor (EGFR) wild-type and anaplastic lymphoma kinase (ALK) negative status, and at least one measurable lesion.

During the clinical trial, participants received Tabrecta 400 mg orally twice daily until disease progression or unacceptable toxicity. The major efficacy outcome measure was overall response rate (ORR), which reflects the percentage of participants who had a certain amount of tumour shrinkage. An additional efficacy outcome measure was duration of response (DOR). The efficacy population included 28 patients who had never undergone treatment for NSCLC and 69 previously treated patients. The ORR for the 28 participants was 68 per cent, with four per cent having a complete response and 64 per cent having a partial response. The ORR for the 69 participants was 41 per cent, with all having a partial response. Of the responding participants, who had never undergone treatment for NSCLC, 47 per cent had a duration of response lasting 12 months or longer compared to 32.1 per cent of the responding participants who had been previously treated.

Common side effects for patients taking Tabrecta are peripheral edema (leg swelling), nausea, fatigue, vomiting, dyspnea (shortness of breath) and decreased appetite.

Tabrecta may cause serious side effects, including interstitial lung disease (a group of lung conditions that causes scarring of lung tissues) or pneumonitis (inflammation of the lung tissue). Tabrecta should be permanently discontinued in patients with these side effects. Tabrecta may also cause hepatotoxicity (damage to liver cells), and healthcare professionals should monitor a patient’s liver function tests prior to starting and when taking Tabrecta. If a patient experiences hepatotoxicity, Tabrecta should be withheld, dose reduced or permanently discontinued. Based on a clear positive signal for phototoxicity (drug-induced damage to cells that is enhanced by UV light) in laboratory studies in cells, patients may be more sensitive to sunlight and should be advised to take precautions to cover their skin and use sunscreen and not to tan while taking Tabrecta.

Tabrecta may cause harm to a developing foetus or new-born baby. Healthcare professionals should advise pregnant women of this risk and should advise both, females of reproductive potential and male patients with female partners of reproductive potential to use effective contraception during treatment with Tabrecta and for one week after the last dose.

“In the face of the COVID-19 pandemic, our regular work on reviewing treatments for patients with cancer is moving forward,” said Pazdur. “The impact may be hardest on those with acute or chronic medical conditions and those with weakened immune systems, such as that caused by cancer and some forms of cancer treatment. We are working to address critical issues for patients with cancer and their healthcare providers and continuing to expedite oncology product development in this critical time.”

Tabrecta was approved under the Acelerated Approval pathway, which provides for the approval of drugs that treat serious or life-threatening diseases and generally provide a meaningful advantage over existing treatments. The FDA granted this 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. Tabrecta received Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases.

The FDA granted approval of Tabrecta to Novartis Pharmaceuticals Corporation. The approval of the F1CDx companion diagnostic was granted to Foundation Medicine, Inc.

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