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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Efficacy
Trial Design: TABRECTA® (capmatinib) tablets was studied in GEOMETRY mono-1, a multicenter, nonrandomized, open-label, multicohort study of patients with EGFR wild-type, ALK-negative, metastatic NSCLC. 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. 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 blinded independent review committee according to Response Evaluation Criteria in Solid Tumors 1.1.1,2
ALK, anaplastic lymphoma kinase; EGFR, epidermal growth factor receptor; MET, mesenchymal-epithelial transition; METex14, MET exon 14 skipping; mNSCLC, metastatic non-small cell lung cancer.
In the GEOMETRY mono-1 pivotal trial, TABRECTA® (capmatinib) tablets delivered an overall response rate (ORR) of 68% and a median duration of response (mDOR) of over 1 year (12.6 months) in treatment-naive patients (n=28).
Start strong with TABRECTA
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.
Please see additional Important Safety Information below.
Other efficacy outcomes
- The majority of patients taking TABRECTA® (capmatinib) tablets 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.
In GEOMETRY mono-1, TABRECTA achieved a disease control rate (DCR) of 96.4% in treatment-naive patients.
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, progression-free survival (PFS) and overall survival (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.
The median PFS within treatment-naive patients in GEOMETRY mono-1 was 12.4 months.
In the same subset of patients, the median OS was 20.8 months.
CR, complete response; NE, not estimable; PD, progressive disease; PR, partial response; SD, stable disease.
*Updated data cutoff as of January 2020.
Important Safety Information (continued)
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.
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)
- 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
- Percentage of patients with responses at ≥12 months was 32%1
Other efficacy outcomes
- Previous treatments included immunotherapy (28%) and chemotherapy (94%), and 23% of patients received 2 prior lines of therapy2
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.
- 78.3% DCR (95% CI, 66.7-87.3)2
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.
- 5.4-month median PFS (95% CI, 4.2-7.0) 60 of 69 (87%) event rate3*
- 13.6-month median OS (95% CI, 8.6-22.2) 47 of 69 (68%) event rate4*
*Updated data cutoff as of January 2020.
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)1,2,5
|
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) |
||
|
19 (28) |
||
|
65 (94) |
||
|
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) |
|
19 (28) |
||
|
65 (94) |
||||
|
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.
Important Safety Information
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.
Please see additional Important Safety Information below.
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 blinded independent review committee.5
Intracranial response with TABRECTA: 54% (n=7 of 13)5
• Complete resolution: 31% (n=4 of 13)
• Partial resolution: 23% (n=3 of 13)
Intracranial disease control rate: 92% (n=12 of 13)5
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; 2022. 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. 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.
