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.

Table 5: Efficacy Results for Treatment-Naïve and Previously Treated Patients in GEOMETRY mono-1
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

TABRECTA (capmatinib) 150 mg and 200 mg tablets
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:
  • has spread to other parts of the body (metastatic), and
  • whose tumors have an abnormal mesenchymal epithelial transition (MET) gene. Your healthcare provider will perform a test to make sure that TABRECTA is right for you.
It is not known if TABRECTA is safe and effective in children.
Before taking TABRECTA, tell your healthcare provider about all of your medical conditions, including if you:
  • have or have had lung or breathing problems other than your lung cancer
  • have or have had liver problems
  • have or have had pancreatic problems
  • are pregnant or plan to become pregnant. TABRECTA can harm your unborn baby.Females who are able to become pregnant:
    • Your healthcare provider should do a pregnancy test before you start your treatment with TABRECTA.
    • You should use effective birth control during treatment and for 1 week after your last dose of TABRECTA. Talk to your healthcare provider about birth control choices that might be right for you during this time.
    • Tell your healthcare provider right away if you become pregnant or think you may be pregnant during treatment with TABRECTA.
    Males who have female partners who can become pregnant:
    • You should use effective birth control during treatment and for 1 week after your last dose of TABRECTA.
  • are breastfeeding or plan to breastfeed. It is not known if TABRECTA passes into your breast milk. Do not breastfeed during treatment and for 1 week after your last dose of TABRECTA.
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.
How should I take TABRECTA?
  • Take TABRECTA exactly as your healthcare provider tells you.
  • Take TABRECTA 2 times a day with or without food.
  • Swallow TABRECTA tablets whole. Do not break, crush, or chew TABRECTA tablets.
  • Do not change your dose or stop taking TABRECTA unless your healthcare provider tells you to.
  • If you miss or vomit a dose of TABRECTA, do not make up the dose. Take your next dose at your regular scheduled time.
What should I avoid while taking TABRECTA?
  • Your skin may be sensitive to the sun (photosensitivity) during treatment with TABRECTA. Use sunscreen or wear clothes that cover your skin during your treatment with TABRECTA to limit direct sunlight exposure.
What are the possible side effects of TABRECTA?TABRECTA may cause serious side effects, including:
  • Lung or breathing problems. TABRECTA may cause inflammation of the lungs that can cause death. Tell your healthcare provider right away if you develop any new or worsening symptoms, including:
◦ cough ◦ fever ◦ trouble breathing or shortness of breath
  • Liver problems. TABRECTA may cause abnormal liver blood test results. Your healthcare provider will do blood tests to check your liver function before you start treatment and during treatment with TABRECTA. Tell your healthcare provider right away if you develop any signs and symptoms of liver problems, including:
◦ 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
  • Pancreas problems. TABRECTA may cause increases in your blood amylase and/or lipase levels that may indicate a problem with your pancreas. Your healthcare provider will do blood tests to check your pancreatic function before you start treatment and during treatment with TABRECTA. Tell your healthcare provider right away if you develop any signs and symptoms of pancreas problems, including:
    • upper stomach (abdominal) pain that may spread to your back and get worse with eating
    • weight loss
    • nausea
    • vomiting
  • Allergic reactions. TABRECTA can cause an allergic reaction. Stop taking TABRECTA and tell your healthcare provider right away if you get any signs and symptoms of an allergic reaction, including:
◦ fever ◦ chills ◦ itching ◦ rash ◦ dizziness or feeling faint ◦ nausea ◦ vomiting
  • Risk of sensitivity to sunlight (photosensitivity). See “What should I avoid while taking TABRECTA?”
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?
  • Store TABRECTA at room temperature between 68°F to 77°F (20°C to 25°C).
  • Store TABRECTA in the original package with the drying agent (desiccant) cartridge.
  • Protect TABRECTA from moisture.
  • Throw away (discard) any unused TABRECTA you have left after 6 weeks of first opening the bottle.
Keep TABRECTA and all medicines out of the reach of children.
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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