Prescription Drug Information: TABRECTA (Page 3 of 4)
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
Carcinogenicity studies were not conducted with capmatinib. Capmatinib was not mutagenic in an in vitro bacterial reverse mutation assay and did not cause chromosomal aberrations in an in vitro chromosome aberration assay in human peripheral blood lymphocytes. Capmatinib was not clastogenic in an in vivo bone marrow micronucleus test in rats.
Dedicated fertility studies were not conducted with capmatinib. No effects on male and female reproductive organs occurred in general toxicology studies conducted in rats and monkeys at doses resulting in exposures of up to approximately 3.6 times the human exposure based on AUC at the 400 mg twice daily clinical dose.
13.2 Animal Toxicology and/or Pharmacology
In rats, capmatinib administration resulted in vacuolation of white matter of the brain in both 4- and 13-week studies at doses ≥ 2.2 times the human exposure (AUC) at the 400 mg twice daily clinical dose. In some cases, the brain lesions were associated with early death and/or convulsions or tremors. Concentrations of capmatinib in the brain tissue of rats was approximately 9% of the corresponding concentrations in plasma.
In vitro and in vivo assays demonstrated that capmatinib has some potential for photosensitization; however, the no-observed-adverse-effect level for in vivo photosensitization was 30 mg/kg/day (Cmax of 14000 ng/mL), about 2.9 times the human Cmax at the 400 mg twice daily clinical dose.
14 CLINICAL STUDIES
Metastatic NSCLC with a Mutation that Leads to MET Exon 14 Skipping
The efficacy of TABRECTA was evaluated in GEOMETRY mono-1, a multicenter, non-randomized, open-label, multi-cohort study (NCT02414139). Eligible patients were required to have NSCLC with a mutation that leads to MET exon 14 skipping, epidermal growth factor receptor (EGFR) wild-type and anaplastic lymphoma kinase (ALK) negative status, and at least one measurable lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Patients with symptomatic CNS metastases, clinically significant uncontrolled cardiac disease, or who received treatment with any MET or hepatocyte growth factor (HGF) inhibitor were not eligible for the study.
Out of the first 97 patients enrolled in GEOMETRY mono-1 following the central confirmation of MET exon 14 skipping by a RNA-based clinical trial assay, 78 patient samples were retested with the FDA-approved FoundationOne® CDx (22 treatment-naïve and 56 previously treated patients) to detect mutations that lead to MET exon 14 skipping. Out of 78 samples retested with FoundationOne® CDx, 73 samples were evaluable (20 treatment-naïve and 53 previously treated patients), 72 (20 treatment-naïve and 52 previously treated patients) of which were confirmed to have a mutation that leads to MET exon 14 skipping, demonstrating an estimated positive percentage agreement of 99% (72/73) between the clinical trial assay and the FDA-approved assay.
Patients received TABRECTA 400 mg orally twice daily until disease progression or unacceptable toxicity. The major efficacy outcome measure was overall response rate (ORR) as determined by a Blinded Independent Review Committee (BIRC) according to RECIST 1.1. An additional efficacy outcome measure was duration of response (DOR) by BIRC.
The efficacy population included 60 treatment-naïve patients and 100 previously treated patients. The median age was 71 years (range: 48 to 90 years); 61% female; 77% White; 25% had Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 and 74% had ECOG PS 1; 61% never smoked; 83% had adenocarcinoma; and 16% had CNS metastases. Among previously treated patients, 81% received one, 16% received two and 3% received three prior lines of systemic therapy. Amongst previously treated patients, 86% received prior platinum-based chemotherapy.
Efficacy results are presented in Table 5.
Abbreviations: CI, confidence interval; NE, not estimable.a Blinded Independent Review Committee (BIRC) review.b Confirmed response.c Clopper and Pearson exact binomial 95% CI.d Based on Kaplan-Meier estimate. | ||
Efficacy parameters | Treatment-naïveN = 60 | Previously treatedN = 100 |
Overall response ratea,b (95% CI)c | 68% (55, 80) | 44% (34, 54) |
Complete response | 5% | 0 |
Partial response | 63% | 44% |
Duration of response (DOR)a | ||
Median (months) (95% CI)d | 16.6 (8.4, 22.1) | 9.7 (5.6, 13.0) |
Patients % with DOR ≥ 12 months | 49% | 36% |
16 HOW SUPPLIED/STORAGE AND HANDLING
How Supplied
Strength | Description | Tablets per bottle | NDC number |
150 mg | Pale orange brown, ovaloid, curved film-coated tablet with beveled edges, unscored, debossed with ‘DU’ on one side and ‘NVR’ on the other side. | 56 | 0078-0709-56 |
200 mg | Yellow, ovaloid, curved film-coated tablet with beveled edges, unscored, debossed with ‘LO’ on one side and ‘NVR’ on the other side. | 56 | 0078-0716-56 |
Storage
Dispense in the original package with the desiccant cartridge. Store at 20°C to 25°C (68°F to 77°F), excursions permitted between 15°C and 30°C (59°F and 86°F) [see USP Controlled Room Temperature]. Protect from moisture.
Discard any unused TABRECTA remaining after 6 weeks of first opening the bottle.
17 PATIENT COUNSELING INFORMATION
Advise the patient to read the FDA-approved patient labeling (Patient Information).
Interstitial Lung Disease (ILD)/Pneumonitis
Inform patients of the risks of severe or fatal ILD/pneumonitis. Advise patients to immediately contact their healthcare provider for new or worsening respiratory symptoms [see Warnings and Precautions (5.1)].
Hepatotoxicity
Inform patients that they will need to undergo lab tests to monitor liver function. Advise patients to immediately contact their healthcare provider for signs and symptoms of liver dysfunction [see Warnings and Precautions (5.2)].
Pancreatic Toxicity
Inform patients that they will need to undergo lab tests to monitor pancreatic function. Advise patients to immediately contact their healthcare provider for signs and symptoms of pancreatitis [see Warnings and Precautions (5.3)].
Hypersensitivity Reactions
Inform patients that there is a risk of hypersensitivity reactions with TABRECTA. Advise patients to stop taking TABRECTA and immediately contact their healthcare provider for signs and symptoms of hypersensitivity [see Warnings and Precautions (5.4)].
Risk of Photosensitivity
Inform patients that there is a potential risk of photosensitivity reactions with TABRECTA. Advise patients to limit direct ultraviolet exposure by using sunscreen or protective clothing during treatment with TABRECTA [see Warnings and Precautions (5.5)].
Embryo-Fetal Toxicity
Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to inform their healthcare provider of a known or suspected pregnancy [see Warnings and Precautions (5.6), Use in Specific Populations (8.1)].
Advise females of reproductive potential to use effective contraception during treatment with TABRECTA and for 1 week after the last dose [see Use in Specific Populations (8.3)].
Advise males with female partners of reproductive potential to use effective contraception during treatment with TABRECTA and for 1 week after the last dose [see Use in Specific Populations (8.3)].
Drug Interactions
Advise patients to inform their healthcare providers of all concomitant medications, including prescription medicines, over-the-counter drugs, vitamins, and herbal products [see Drug Interactions (7)].
Lactation
Advise women not to breastfeed during treatment with TABRECTA and for 1 week after the last dose [see Use in Specific Populations (8.2)].
Distributed by:
Novartis Pharmaceuticals CorporationEast Hanover, New Jersey 07936
© Novartis
T2024-19
This Patient Information has been approved by the U.S. Food and Drug Administration. | Revised: 3/2023 | |
PATIENT INFORMATIONTABRECTA® (ta brek tah)(capmatinib) tablets | ||
What is TABRECTA? TABRECTA is a prescription medicine used to treat adults with a kind of lung cancer called non-small cell lung cancer (NSCLC) that:
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Before taking TABRECTA, tell your healthcare provider about all of your medical conditions, including if you:
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How should I take TABRECTA?
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What should I avoid while taking TABRECTA?
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What are the possible side effects of TABRECTA?TABRECTA may cause serious side effects, including:
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◦ cough | ◦ fever | ◦ trouble breathing or shortness of breath |
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◦ your skin or the white part of your eyes turns yellow (jaundice) ◦ dark or “tea-colored” urine ◦ light-colored stools (bowel movements) ◦ confusion ◦ tiredness ◦ loss of appetite for several days or longer | ◦ nausea and vomiting ◦ pain, aching, or tenderness on the right side of your stomach-area (abdomen) ◦ weakness ◦ swelling in your stomach-area | |
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◦ fever ◦ chills ◦ itching ◦ rash | ◦ dizziness or feeling faint ◦ nausea ◦ vomiting | |
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The most common side effects of TABRECTA include: | ||
• swelling of your hands or feet • nausea • muscle or bone pain • tiredness and weakness • vomiting | • trouble breathing • cough • loss of appetite • changes in certain blood tests | |
Your healthcare provider may change your dose, temporarily stop, or permanently stop treatment with TABRECTA if you develop certain side effects.These are not all of the possible side effects of TABRECTA.Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. | ||
How should I store TABRECTA?
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General information about the safe and effective use of TABRECTA. Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use TABRECTA for a condition for which it was not prescribed. Do not give TABRECTA to other people, even if they have the same symptoms you have. It may harm them. You can ask your pharmacist or healthcare provider for information about TABRECTA that is written for health professionals. | ||
What are the ingredients in TABRECTA? Active ingredient: capmatinibInactive ingredients: Tablet core: colloidal silicon dioxide; crospovidone; magnesium stearate; mannitol; microcrystalline cellulose; povidone; and sodium lauryl sulfate.Tablet coating (150 mg): ferric oxide, red; ferric oxide, yellow; ferrosoferric oxide; hypromellose; polyethylene glycol (PEG) 4000; talc; and titanium dioxide.Tablet coating (200 mg): ferric oxide, yellow; hypromellose; polyethylene glycol (PEG) 4000; talc; and titanium dioxide.Distributed by: Novartis Pharmaceuticals Corporation, East Hanover, New Jersey 07936For more information, go to www.TABRECTA.com or call 1-844-638-5864.© Novartis |
T2023-16
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