Safety Profile of TABRECTA
Common adverse reactions (≥10%) across all cohorts in GEOMETRY mono-12,3
TABRECTA® (capmatinib) tablets (N=373) | |||
COMMON ADVERSE REACTIONS | ALL GRADES (%) | GRADE 3 (%) | GRADE 4 (%) |
General disorders and administration-site conditions | |||
Edemaa | 59 | 13 | - |
Musculoskeletal painb | 40 | 4.3 | - |
Fatiguec | 34 | 8 | - |
Pyrexiad | 14 | 0.8 | - |
Weight decreased | 11 | 0.5 | - |
Gastrointestinal disorders | |||
Nausea | 46 | 2.4 | - |
Vomiting | 28 | 2.4 | - |
Constipation | 19 | 0.8 | - |
Diarrhea | 19 | 0.5 | - |
Respiratory, thoracic, and mediastinal disorders | |||
Dyspnea | 25 | 7* | 0.5 |
Coughe | 21 | 0.5 | - |
Pneumoniaf | 13 | 6* | 0.5 |
Metabolism and nutrition disorders | |||
Decreased appetite | 21 | 1.1 | - |
Skin and subcutaneous tissue disorders | |||
Rashg | 13 | 0.5 | - |
Nervous system disorders | |||
Dizzinessh | 13 | 0.5 | - |
aEdema includes edema peripheral, generalized edema, face edema, edema, localized edema, edema genital, eyelid edema, peripheral swelling, scrotal edema, and penile edema.
bMusculoskeletal pain includes arthralgia, back pain, bone pain, musculoskeletal chest pain, musculoskeletal pain, myalgia, neck pain, noncardiac chest pain, pain in extremity, pain in jaw, spinal pain.
cFatigue includes fatigue and asthenia.
dPyrexia includes pyrexia and body temperature increased.
eCough includes cough, upper airway cough syndrome, and productive cough.
fPneumonia includes pneumonia aspiration, pneumonia, pneumonia influenzal, pneumonia bacterial, lower respiratory tract infection, and lung abscess.
gRash includes rash, dermatitis acneiform, rash maculo-papular, eczema, erythema multiforme, rash macular, dermatitis, rash erythematous, rash pustular, dermatitis bullous, and rash vesicular.
hDizziness includes dizziness, vertigo, and vertigo positional.
*Includes both grade 3 and 4.
The majority of patients who reported adverse reactions (ARs) remained on TABRECTA® (capmatinib) tablets.2
Dose reductions due to ARs occurred in 26% of patients, and dose interruptions due to ARs occurred in 57% of patients2
Sixty-five patients (17%) treated with TABRECTA® (capmatinib) tablets discontinued therapy due to ARs2,3
The most frequent ARs (≥1%) leading to permanent discontinuation of TABRECTA were ILD/pneumonitis (2.4%), edema (2.4%), fatigue (1.3%), and pneumonia (1.1%)
Fatal ARs occurred in 0.5% of patients who received TABRECTA, including pneumonitis (0.3%) and death, not otherwise specified (0.3%).2
Clinically relevant ARs occurring in <10% of patients treated with TABRECTA® (capmatinib) tablets included pruritus (including allergic pruritus), ILD/pneumonitis, cellulitis, acute kidney injury (including renal failure), urticaria, and acute pancreatitis.2
Serious hypersensitivity reactions and thrombocytopenia occurred in patients treated with TABRECTA® (capmatinib) tablets in clinical trials other than GEOMETRY mono-1.2
Select laboratory abnormalities (≥20%) worsening from baseline in patients who received TABRECTA® (capmatinib) tablets in GEOMETRY mono-12
| TABRECTA® (capmatinib) tabletsa | |
LABORATORY ABNORMALITIES | Grades 1 to 4 (%) | Grades 3 to 4 (%) |
Chemistry | ||
Decreased albumin | 72 | 1.9 |
Increased creatinine | 65 | 0.5 |
Increased alanine aminotransferase | 39 | 9 |
Increased amylase | 34 | 4.7 |
Increased alkaline phosphatase | 32 | 0.6 |
Increased gamma-glutamyltransferase | 30 | 6 |
Increased lipase | 29 | 9 |
Increased aspartate aminotransferase | 28 | 6 |
Decreased phosphate | 26 | 4.4 |
Increased potassium | 25 | 4.1 |
Decreased sodium | 24 | 6 |
Decreased glucose | 23 | 0.3 |
Hematology | ||
Decreased lymphocytes | 45 | 14 |
Decreased leukocytes | 25 | 1.7 |
Decreased hemoglobin | 24 | 2.8 |
aThe denominator used to calculate the rate varied from 359 to 364 based on the number of patients with a baseline value and at least 1 post-treatment value.
Select ARs can be managed with dose modifications2
ADVERSE REACTION | SEVERITY | DOSE MODIFICATION |
ILD/pneumonitis | Any grade | Permanently discontinue TABRECTA |
Increased ALT and/or AST without increased total bilirubin | Grade 3 | Withhold TABRECTA until recovery to baseline ALT/AST
If recovered to baseline within 7 days, then resume TABRECTA at the same dose; otherwise, resume TABRECTA at a reduced dose |
Grade 4 | Permanently discontinue TABRECTA | |
Increased ALT and/or AST with increased total bilirubin in the absence of cholestasis or hemolysis | ALT and/or AST greater than 3 times ULN with total bilirubin greater than 2 times ULN | Permanently discontinue TABRECTA |
Increased total bilirubin without concurrent increased ALT and/or AST | Grade 2 | Withhold TABRECTA until recovery to baseline bilirubin
If recovered to baseline within 7 days, then resume TABRECTA at the same dose; otherwise, resume TABRECTA at a reduced dose |
Grade 3 | Withhold TABRECTA until recovery to baseline bilirubin
If recovered to baseline within 7 days, then resume TABRECTA at a reduced dose; otherwise, permanently discontinue TABRECTA | |
Grade 4 | Permanently discontinue TABRECTA | |
Increased lipase or amylase | Grade 3 | Withhold TABRECTA until ≤grade 2 or baseline
If recovered to baseline or ≤grade 2 within 14 days, resume TABRECTA at a reduced dose; otherwise, permanently discontinue TABRECTA |
Grade 4 | Permanently discontinue TABRECTA | |
Pancreatitis | Grade 3 or grade 4 | Permanently discontinue TABRECTA |
Hypersensitivity | All grades | If hypersensitivity is suspected based on clinical judgment, withhold TABRECTA until resolution of the event
Permanently discontinue TABRECTA in patients who develop serious hypersensitivity reactions |
Other adverse reactions | Grade 2 | Maintain dose level. If intolerable, consider withholding TABRECTA until resolved, then resume TABRECTA at a reduced dose |
Grade 3 | Withhold TABRECTA until resolved, then resume TABRECTA at a reduced dose | |
Grade 4 | Permanently discontinue TABRECTA |
ALT, alanine aminotransferase; AST, aspartate aminotransferase; ULN, upper limit of normal.
Although the exact mechanism is unknown, the MET inhibitor TABRECTA may cause edema2
In the GEOMETRY mono-1 clinical trial, edema occurred in 59% of patients and was managed based on severity2,4:
Grade ≤2 peripheral edema: Consider measures such as leg elevation, compression stockings, or dietary salt modification
Grade ≥3 peripheral edema: Initiate or intensify the above measures
Edema was one of the most common ARs in GEOMETRY mono-1, leading to discontinuation in 2.4% of patients.2
Edema is a common AR and its management may help patients remain on treatment |