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Important Safety Information:


Interstitial Lung Disease (ILD)/Pneumonitis.
ILD/pneumonitis, which can be fatal, occurred in patients treated with TABRECTA® (capmatinib) tablets. ILD/pneumonitis occurred in 4.5% of patients trea...

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Indication
TABRECTA® (capmatinib) tablets is indicated for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have a mutation that leads to mesenchymal-epithelial transition (MET) exon 14 skipping as detected by an FDA-approved test.

This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

Choose TABRECTA® (capmatinib) tablets, the first FDA-approved targeted treatment for METex14 in mNSCLC

TABRECTA® (capmatinib) tablets delivered a nearly 70% overall response rate in treatment-naive patients (n=28)

TABRECTA® (capmatinib) tablets overall response rate and median duration of response in treatment-naïve patients

Highlights of Important Safety Information

TABRECTA has Warrnings and Precautions for interstitial lung disease (ILD/pneumonitis), hepatotoxicity, risk of photosensitivity, and embryo-fetal toxicity.

The most common adverse reactions (≥20%) are peripheral edema, nausea, fatigue, vomiting, dyspnea, and decreased appetite.

Please see additional Important Safety Information below.

 

Other Efficacy Outcomes

  • The majority of patients taking TABRECTA responded within 7 weeks2

DCR was an exploratory efficacy outcome that accounted for CR + PR + SD + non-CR/non-PD, which may reflect the natural history of disease in an individual patient rather than the therapeutic effect of the treatment.

96.4% disease control rate (95% CI, 81.7-99.9)

Noncomparative analysis of median PFS and OS

This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

Due to the nonrandomized, noncomparative nature of the study, PFS and OS results are difficult to interpret. No statistical tests were made for PFS and OS, as there was no comparator arm. PFS and OS results are based on an interim analysis; results are subject to change pending longer trial follow-up.

12.4-month median progression-free survival (95%CI, 8.2-NE)
20.8-month median overall survival (95% CI, 12.4-NE)

 

CR, complete response; DCR, disease control rate; mDOR, median duration of response; NE, not estimable; ORR, overall response rate; OS, overall survival; PD, progressive disease; PFS, progression-free survival; PR, partial response; SD, stable disease.
*Updated data cutoff as of January 2020.

Efficacious and sustained overall responses with TABRECTA in previously treated patients (n=69)

  • 41% achieved an overall response (95% CI, 29-53; CR, 0 [0%] + PR, 28 [41%])1,2
  • 9.7-month mDOR (95% CI, 5.5-13.0; n=28)1

Trial design

TABRECTA was studied in GEOMETRY mono-1, a multicenter, nonrandomized, open-label, multicohort study of patients with EGFR wild-type, ALK-negative mNSCLC. Patients with METex14 (n=97) comprised 2 cohorts: treatment naive (n=28) and treated previously with 1 or 2 prior lines of therapy (n=69). Patients received TABRECTA 400 mg twice daily. Treatment was continued until disease progression, drug intolerance, or investigator-led discontinuation. Patients with symptomatic CNS metastases, clinically significant uncontrolled cardiac disease, or who received treatment with any MET or HGF inhibitor were not eligible for the study. Evaluable patients were defined as those who completed at least 6 cycles of treatment (18 weeks) or discontinued treatment earlier. The major efficacy outcome was overall response rate, and duration of response was an additional efficacy outcome as determined by a BIRC according to RECIST 1.1.1,2

ALK, anaplastic lymphoma kinase; BIRC, blinded independent review committee; CDx, companion diagnostic; CNS, central nervous system; EGFR, epidermal growth factor receptor; HGF, hepatocyte growth factor; RECIST, Response Evaluation Criteria in Solid Tumors.

Discover the efficacy and safety of TABRECTA as a first-line therapy

Common adverse reactions (≥10%) across all cohorts in GEOMETRY mono-11

 

TABRECTA (N=334)

COMMON ADVERSE REACTIONS

ALL GRADES (%)

GRADE 3 (%)

GRADE 4 (%)

General disorders and administration-site conditions

Peripheral edemaa

52

9

-

Fatigueb

32

8

-

Noncardiac chest painc

15

2.1

-

Back pain

14

0.9

-

Pyrexiad

14

0.6

-

Weight decreased

10

0.6

-

Gastrointestinal disorders

 

Nausea

44

2.7

-

Vomiting

28

2.4

-

Constipation

18

0.9

-

Diarrhea

18

0.3

-

Respiratory, thoracic, and mediastinal disorders

 

Dyspnea

24

7

0.6

Cough

16

0.6

-

Metabolism and nutrition disorders

 

Decreased appetite

21

0.9

-

 

aPeripheral edema includes peripheral swelling, peripheral edema, and fluid overload.

bFatigue includes fatigue and asthenia.

cNoncardiac chest pain includes chest discomfort, musculoskeletal chest pain, noncardiac chest pain, and chest pain.

dPyrexia includes pyrexia and body temperature increased.

 

The majority of patients who reported adverse reactions (ARs) remained on TABRECTA.1

  • Dose reductions due to ARs occurred in 23% of patients, and dose interruptions due to ARs occurred in 54% of patients1
  • 54 patients (16%) treated with TABRECTA discontinued therapy due to ARs1,2
    • Most common ARs leading to discontinuation were peripheral edema (1.8%), pneumonitis (1.8%), fatigue (1.5%), alanine aminotransferase increased (0.9%), aspartate aminotransferase increased (0.9%), nausea (0.9%), vomiting (0.9%), blood bilirubin increased (0.6%), blood creatinine increased (0.6%), general physical health deterioration (0.6%), interstitial lung disease (0.6%), organizing pneumonia (0.6%), and pneumonia (0.6%). A fatal AR occurred in 1 patient (0.3%) due to pneumonitis

 

Metastases in the brain

Brain with lesion
  • Intracranial response rate is defined in clinical settings as the percentage of patients with complete or partial resolution of brain lesions. Intracranial response assesses the response of lesions in the brain after a specific scan5,6
  • Intracranial disease control rate accounts for complete resolution, partial resolution, stable disease, and incomplete response/non-progressive disease, which may reflect the natural history of the disease in an individual patient5

Do you consider intracranial response rates when choosing a METex14 treatment for your patients with mNSCLC?

In a post hoc analysis, intracranial responses were observed with TABRECTA in patients with brain lesions at baseline (n=13).7

Thirteen evaluable patients in the cohorts with METex14 (n=97) had brain metastases at baseline, as assessed by a BIRC.7

Intracranial response with TABRECTA: 54% (n=7 of 13)7

  • Complete resolution: 31% (n=4 of 13)
  • Partial resolution: 23% (n=3 of 13)

Intracranial disease control rate: 92% (n=12 of 13)7

Intracranial disease control rate was an exploratory efficacy outcome that accounted for CR + PR + SD + non-CR/non-PD, and may reflect the natural history of disease in an individual patient rather than the therapeutic effect of the treatment.

 

This analysis of overall intracranial response rate included patients with measurable brain disease at baseline and at least one postbaseline assessment but omits brain imaging in patients with premature discontinuations, which may lead to bias favoring a treatment effect.

If brain lesions were documented at baseline, computed tomography (CT) with intravenous contrast or a magnetic resonance imaging scan was mandated every 6 weeks, or otherwise, only if clinically indicated.2

Results are based on a noncomparative post hoc analysis and are observational in nature; as such, they should be interpreted with caution.

 

References: 1. Tabrecta [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp; 2020. 2. Data on file. Study CINC280A2201. Novartis Pharmaceuticals Corp; 2019. 3. Wolf J, Seto T, Han J-Y, et al. Capmatinib in MET exon 14–mutated or MET-amplified non–small-cell lung cancer. N Engl J Med. 2020;383(10):944-957. 4. Data on file. Study CINC280A2201, January 2020. Novartis Pharmaceuticals Corp; 2020. 5. Villaruz LC, Socinski MA. The clinical viewpoint: definitions, limitations of RECIST, practical considerations of measurement. Clin Cancer Res. 2013;19(10):2629-2636. 6. Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45(2):228-247. 7. Wolf J, Seto T, Han J-Y, et al. Capmatinib in METex14-mutated advanced non-small cell lung cancer (NSCLC): Efficacy data from the phase II GEOMETRY mono-1 study. Abstract 9004. Presented at: 2019 ASCO Annual Meeting; May 31-June 4, 2019; Chicago, IL.

Indication

TABRECTA® (capmatinib) tablets is indicated for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have a mutation that leads to mesenchymal-epithelial transition (MET) exon 14 skipping as detected by an FDA-approved test.

 

This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.


Important Safety Information

Interstitial Lung Disease (ILD)/Pneumonitis. ILD/pneumonitis, which can be fatal, occurred in patients treated with TABRECTA. ILD/pneumonitis occurred in 4.5% of patients treated with TABRECTA in the GEOMETRY mono-1 study, with 1.8% of patients experiencing grade 3 ILD/pneumonitis and 1 patient experiencing death (0.3%). Eight patients (2.4%) discontinued TABRECTA due to ILD/pneumonitis.

 

Monitor for new or worsening pulmonary symptoms indicative of ILD/pneumonitis (eg, dyspnea, cough, fever). Immediately withhold TABRECTA in patients with suspected ILD/pneumonitis and permanently discontinue if no other potential causes of ILD/pneumonitis are identified.

 

Hepatotoxicity. Hepatotoxicity occurred in patients treated with TABRECTA. Increased alanine aminotransferase (ALT)/aspartate aminotransferase (AST) occurred in 13% of patients treated with TABRECTA in GEOMETRY mono-1. Grade 3 or 4 increased ALT/AST occurred in 6% of patients. Three patients (0.9%) discontinued TABRECTA due to increased ALT/AST.

 

Monitor liver function tests (including ALT, AST, and total bilirubin) prior to the start of TABRECTA, every 2 weeks during the first 3 months of treatment, then once a month or as clinically indicated, with more frequent testing in patients who develop increased transaminases or bilirubin. Based on the severity of the adverse reaction, withhold, reduce dose, or permanently discontinue TABRECTA.

 

Risk of Photosensitivity. Based on findings from animal studies, there is a potential risk of photosensitivity reactions with TABRECTA. In GEOMETRY mono-1, it was recommended that patients use precautionary measures against ultraviolet exposure, such as use of sunscreen or protective clothing, during treatment with TABRECTA. Advise patients to limit direct ultraviolet exposure during treatment with TABRECTA.

 

Embryo-Fetal Toxicity. Based on findings from animal studies and its mechanism of action, TABRECTA can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with TABRECTA and for 1 week after the last dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with TABRECTA and for 1 week after the last dose.

 

Most Common Adverse Reactions. The most common adverse reactions (≥20%) were peripheral edema (52%), nausea (44%), fatigue (32%), vomiting (28%), dyspnea (24%), and decreased appetite (21%). The most common grade 3 adverse reactions (≥2%) were peripheral edema (9%), fatigue (8%), dyspnea (7%), nausea (2.7%), vomiting (2.4%), and noncardiac chest pain (2.1%). Grade 4 dyspnea was reported in 0.6% of patients.  

 

Clinically Relevant Adverse Reactions. Clinically relevant adverse reactions observed in <10% of patients were pruritus (allergic and generalized), ILD/pneumonitis, cellulitis, acute kidney injury (including renal failure), urticaria, and acute pancreatitis.

 

Laboratory Abnormalities. Select laboratory abnormalities (≥20%) worsening from baseline in patients who received TABRECTA were decreased albumin (68%), increased creatinine (62%), decreased lymphocytes (44%), increased ALT (37%), increased alkaline phosphatase (32%), increased amylase (31%), increased gamma-glutamyltransferase (29%), increased lipase (26%), increased AST (25%), decreased hemoglobin (24%), decreased leukocytes (23%), decreased sodium (23%), decreased phosphate (23%), increased potassium (23%), and decreased glucose (21%).

 

Please see full Prescribing Information for TABRECTA.