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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.

Efficacy

GEOMETRY mono-1 Study

A multicohort, nonrandomized, open-label Phase II trial1,2

TABRECTA™ (capmatinib) tablets was studied in a multicohort, nonrandomized, open-label Phase II trial, GEOMETRY mono-1 TABRECTA™ (capmatinib) tablets was studied in a multicohort, nonrandomized, open-label Phase II trial, GEOMETRY mono-1

 

Major efficacy outcome

  • Overall response rate*

Additional efficacy outcome

  • Duration of response*

Other outcomes

  • Time to response
  • Disease control rate
  • Progression-free survival
  • Overall survival
  • Safety

Patients were enrolled in trial cohorts 4 and 5b after central confirmation of MET exon 14 skipping by an RNA-based clinical trial assay using RT-PCR.1,2

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.1

ALK, anaplastic lymphoma kinase; CNS, central nervous system; EGFR, epidermal growth factor receptor; HGF, hepatocyte growth factor; MET, mesenchymal-epithelial transition; NSCLC, non-small cell lung cancer; RT-PCR, reverse transcription-polymerase chain reaction.

*As determined by a blinded independent review committee (BIRC) according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
Evaluable patients were defined as those who completed at least 6 cycles of treatment (18 weeks) or discontinued treatment earlier.

Patient Characteristics

TABRECTA™ (capmatinib) tablets was studied in patients with MET exon 14 skipping in mNSCLC with a clinically diverse profile

Characteristics of study population with METex14 (n=97)1-3

DEMOGRAPHICS

Median age (range), years

71 (49-90)

Sex, n (%)

Female  

58 (60)

Male

39 (40)

Race, n (%)

White  

73 (75)

Asian

23 (24)

Other  

1 (1)

PATIENT CHARACTERISTICS

Smoking history, n (%)

Never smoked

58 (60)

Former smoker

36 (37)

Current smoker

3 (3)

ECOG status, n (%)

0

23 (24)

1

73 (75)

≥2

1 (1)

Treatment history, n (%)

Treatment naive

28 (29)

Previously treated

69 (71)

  • Prior immunotherapy

19 (28)

  • Prior chemotherapy

65 (94)

  • 2 prior lines of therapy

16 (23)

DISEASE CHARACTERISTICS

Histology, n(%)

Adenocarcinoma

78 (80)

Squamous

8 (8)

Othera

11 (11)

Metastatic site of cancer, n (%)

Bone

57 (59)

Liver

20 (21)

Adrenala

17 (18)

Brainb

13 (12)

DEMOGRAPHICS

PATIENT CHARACTERISTICS

DISEASE CHARACTERISTICS

Median age (range), years

Smoking history, n (%)

Histology, n (%)

71 years (49-90)

Never smoked

58 (60)

Adenocarcinoma

78 (80)

   

Former smoker

36 (37)

Squamous

8 (8)

   

Current smoker

3 (3)

Othera

11 (11)

Sex, n (%)

ECOG status, n (%)

Metastatic site of cancer, n (%)

Female

58 (60)

0

23 (24)

Bone

57 (59)

Male

39 (40)

1

73 (75)

Liver

20 (21)

   

2

1 (1)

Adrenal

17 (18)

   

 

 

Brainb

13 (12)

Race, n (%)

Treatment history, n (%)

White

73 (75)

Treatment naive

28 (29)

Asian

23 (24)

Previously treated

69 (71)

Other

1 (1)

  • Prior immunotherapy

19 (28)

 
  • Prior chemotherapy

65 (94)

  • 2 prior lines of therapy

16 (23)

 

ECOG, Eastern Cooperative Oncology Group; mNSCLC, metastatic non-small cell lung cancer.
aAll other histologies, including 5 sarcomatoid/carcinosarcoma.
bTwelve identified in medical history and 2 identified during baseline computed tomography (CT) scan.

Treatment-Naive Patients

Powerful and sustained overall responses with TABRECTA™ (capmatinib) tablets in treatment-naive patients (n=28)

 

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

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

Other efficacy outcomes

  • The majority of patients taking TABRECTA responded within 7 weeks2
96.4% disease control rate

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.

 

Highlights of Important Safety Information

TABRECTA has Warnings 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.

 

Previously Treated Patients

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

 

TABRECTA™ (capmatinib) tablets overall response rate and median duration of response in previously treated patients

TABRECTA™ (capmatinib) tablets overall response rate and median duration of response in previously treated patients

Other efficacy outcomes2

  • Previous treatments included immunotherapy (28%) and chemotherapy (94%), and 23% of patients received 2 prior lines of therapy
78.3% disease control rate
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.

 

CR, complete response; DCR, disease control rate; NE, not estimable; PD, progressive disease; PR, partial response; SD, stable disease.

Additional Analysis

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

Thirteen evaluable patients in the cohorts with MET exon 14 skipping (n=97) had brain metastases at baseline, as assessed by a BIRC.3

 

Intracranial response with TABRECTA: 54% (n=7 of 13)3

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

Intracranial disease control rate: 92% (n=12 of 13)3

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, 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, 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.

 

Next: Safety Profile

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.