FDA Approval: Capmatinib (Tabrecta) for Lung Cancer

The approval, in the FDA's own words

The FDA approval package for NDA 213591 gives the date as 6 May 2020 and the drug as Tabrecta, capmatinib, in 150 mg and 200 mg tablets from Novartis.

It states the indication as: a kinase inhibitor indicated for the treatment of adult patients with metastatic non-small cell lung cancer whose tumors have a mutation that leads to mesenchymal-epithelial transition (MET) exon 14 skipping as detected by an FDA-approved test.

That last clause is the one people skip, and it is the one that decides eligibility. This drug is not for lung cancer. It is for one molecular change inside a lung cancer, found by a specific kind of test.

Approval at a glance

Field	Detail
Drug	Capmatinib (Tabrecta)
Application	NDA 213591
Regulator	FDA
Approval date	6 May 2020
Class	Kinase inhibitor targeting MET
Eligible group	Adults with metastatic NSCLC carrying a MET exon 14 skipping mutation
Approval route	Accelerated approval
Basis	Overall response rate and duration of response
Dose	400 mg by mouth twice daily

What MET exon 14 skipping actually is

MET is a receptor on the cell surface. Normally it takes a growth signal, passes it inward, and is then switched off and cleared away. Exon 14 is a stretch of the MET gene that codes for the part of the receptor responsible for that shutdown.

Some tumors carry a mutation that causes the cell to leave exon 14 out when it builds the receptor. The result is a MET receptor that works but cannot be turned off. The growth signal stays on.

Capmatinib blocks MET's signalling machinery. Where a tumor's growth depends on that stuck-on receptor, blocking it can shrink the tumor quickly.

This change appears in roughly three to four percent of non-small cell lung cancers, which is why it is missed unless it is looked for. It is not visible on a scan or under a microscope. Finding it requires molecular testing of the tumor, and NCI's clinical summary lists it among the alterations that guide treatment choice in NSCLC. Our page on biomarker testing explains what those panels do.

The trial behind the approval

The label describes the study, GEOMETRY mono-1. The efficacy population had two parts: 28 patients who had not been treated before, and 69 who had.

Neither group had a comparison arm. Everybody received capmatinib, and the measure was how many tumors shrank.

Among patients who had not been treated before, the overall response rate assessed by a blinded independent review committee was 68%, with a 95% confidence interval of 48% to 84%. Among previously treated patients it was 41%, confidence interval 29% to 53%.

Median duration of response was 12.6 months in the untreated group and 9.7 months in the previously treated group. Of those who responded, 47% and 32% respectively were still responding at 12 months.

The group studied was older than people often assume: median age 71, range 49 to 90. Sixty percent were women, 60% had never smoked, 80% had adenocarcinoma, and 12% had cancer that had reached the brain.

Why the test matters as much as the drug

The label describes how the companion diagnostic was validated. Of 78 patient samples retested with the FDA-approved FoundationOne CDx assay, 73 were evaluable, and 72 of those confirmed a MET exon 14 skipping mutation — an agreement of 99% with the trial's own assay.

That detail exists because eligibility here is entirely defined by a laboratory result. Without the test there is no way to know whether this drug has any chance of working, and treating without it would be guessing.

What taking it involves

Capmatinib is 400 mg by mouth twice a day, with or without food, tablets swallowed whole. If a dose is missed or vomited, the label says not to make it up. That is what the label says. Follow the prescription you were given, and tell the clinic if you miss or bring up a dose.

Treat that as the label's reference figure. The amount you swallow is set by your own oncology team, and they change it when side effects or other medicines call for it.

Two warnings drive the monitoring. Interstitial lung disease — inflammation and scarring of lung tissue — occurred in 4.5% of patients on the trial, was severe in 1.8%, and caused one death. New or worsening breathlessness, cough, or fever needs reporting immediately, and the drug is stopped permanently if no other cause is found.

Liver injury is the second. Raised liver enzymes occurred in 13% of patients and were severe in 6%. The label instructs checking liver tests before starting, every two weeks for the first three months, then monthly.

The label also warns about sensitivity to sunlight and about harm to a developing fetus, and sets out two step-downs in dose before stopping altogether.

What this does and doesn't change

For the small group of people whose lung cancer carries this mutation, this replaced chemotherapy as a first option with a tablet taken at home, and roughly two-thirds of previously untreated tumors shrank.

It changes nothing for the other 96 or so percent of non-small cell lung cancers, and nothing for small cell lung cancer. Its practical effect for most people is upstream: it is one more reason that molecular testing of an advanced lung cancer is part of the diagnosis, not an optional extra.

What to keep in perspective

• A response rate measures tumor shrinkage, not length of life. Single-arm trials cannot show survival benefit, and this was an accelerated approval on that basis.
• The confidence interval on the untreated group is wide — 48% to 84% — because only 28 people were in it.
• Targeted drugs of this class typically stop working eventually, as resistant cells emerge. The question of what comes next is part of the plan from the start.
• Trial participants were selected and were well enough to enrol. Results may not carry over to everyone with this mutation.

Questions worth asking

• Has my tumor had molecular testing, and does the report mention MET?
• If I start this, how will we monitor my lungs and liver, and what symptoms should I call about?
• What are the options if it stops working?

Our guides to lung cancer and targeted therapy cover the background.

Sources

• FDA approval package, NDA 213591 (TABRECTA, capmatinib)
• FDA prescribing information (2020): TABRECTA (capmatinib) tablets
• FDA Drugs@FDA overview: TABRECTA, NDA 213591
• NCI PDQ: Non-Small Cell Lung Cancer Treatment (Health Professional Version)

How this article was prepared

An AI-assisted editorial system helped prepare this page. No named medical reviewer has reviewed it unless one is listed.

Cancer Explained is published by the National Cancer Information Foundation. It is not medical advice and does not suggest a test or treatment.

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