Tafinlar

TAFINLAR- dabrafenib mesylate capsule
TAFINLAR- dabrafenib mesylate tablet, for suspension
Novartis Pharmaceuticals Corporation

1 INDICATIONS AND USAGE

1.1 BRAF V600E Mutation-Positive Unresectable or Metastatic Melanoma

TAFINLAR^® is indicated as a single agent for the treatment of patients with unresectable or metastatic melanoma with BRAF V600E mutation as detected by an FDA-approved test.

1.2 BRAF V600E or V600K Mutation-Positive Unresectable or Metastatic Melanoma

TAFINLAR is indicated, in combination with trametinib, for the treatment of patients with unresectable or metastatic melanoma with BRAF V600E or V600K mutations, as detected by an FDA-approved test [see Dosage and Administration (2.1)].

1.3 Adjuvant Treatment of BRAF V600E or V600K Mutation-Positive Melanoma

TAFINLAR is indicated, in combination with trametinib, for the adjuvant treatment of patients with melanoma with BRAF V600E or V600K mutations, as detected by an FDA-approved test, and involvement of lymph node(s), following complete resection [see Dosage and Administration (2.1)].

1.4 BRAF V600E Mutation-Positive Metastatic NSCLC

TAFINLAR is indicated, in combination with trametinib, for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) with BRAF V600E mutation as detected by an FDA-approved test [see Dosage and Administration (2.1)].

1.5 BRAF V600E Mutation-Positive Locally Advanced or Metastatic Anaplastic Thyroid Cancer

TAFINLAR is indicated, in combination with trametinib, for the treatment of patients with locally advanced or metastatic anaplastic thyroid cancer (ATC) with BRAF V600E mutation and with no satisfactory locoregional treatment options [see Dosage and Administration (2.1)].

​1.6 BRAF V600E Mutation-Positive Unresectable or Metastatic Solid Tumors

​TAFINLAR is indicated, in combination with trametinib, for the treatment of adult and pediatric patients 1 year of age and older with unresectable or metastatic solid tumors with BRAF V600E mutation who have progressed following prior treatment and have no satisfactory alternative treatment options [see Dosage and Administration (2.1)]. This indication is approved under accelerated approval based on overall response rate (ORR) and duration of response (DoR) [see Clinical Studies (14.6)]. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

​1.7 BRAF V600E Mutation-Positive Low-Grade Glioma

​TAFINLAR is indicated, in combination with trametinib, for the treatment of pediatric patients 1 year of age and older with low-grade glioma (LGG) with a BRAF V600E mutation who require systemic therapy [see Dosage and Administration (2.1)].

1.8 Limitations of Use

• TAFINLAR is not indicated for treatment of patients with colorectal cancer because of known intrinsic resistance to BRAF inhibition [see Indications and Usage (1.6), Clinical Pharmacology (12.1)].
• TAFINLAR is not indicated for treatment of patients with wild-type BRAF solid tumors [see Warnings and Precautions (5.2)].

2 DOSAGE AND ADMINISTRATION

2.1 Patient Selection

Melanoma

• Confirm the presence of BRAF V600E mutation in tumor specimens prior to initiation of treatment with TAFINLAR as a single agent [see Warnings and Precautions (5.2), Clinical Studies (14.1)].
• Confirm the presence of BRAF V600E or V600K mutation in tumor specimens prior to initiation of treatment with TAFINLAR and trametinib [see Warnings and Precautions (5.2), Clinical Studies (14.2, 14.3)].
• Information on FDA-approved tests for the detection of BRAF V600 mutations in melanoma is available at: http://www.fda.gov/CompanionDiagnostics.

NSCLC

• Confirm the presence of BRAF V600E mutation in tumor specimens prior to initiation of treatment with TAFINLAR and trametinib [see Clinical Studies (14.4)].
• Information on FDA-approved tests for the detection of BRAF V600E mutations in NSCLC is available at: http://www.fda.gov/CompanionDiagnostics.

ATC

• Confirm the presence of BRAF V600E mutation in tumor specimens prior to initiation of treatment with TAFINLAR and trametinib [see Clinical Studies (14.5)]. An FDA-approved test for the detection of BRAF V600E mutation in ATC is not currently available.

Solid Tumors

• ​Confirm the presence of BRAF V600E mutation in tumor specimens prior to initiation of treatment with TAFINLAR and trametinib [see Clinical Studies (14.6)]. An FDA-approved test for the detection of BRAF V600E mutation in solid tumors other than melanoma and NSCLC is not currently available.

Low-Grade Glioma

• ​Confirm the presence of BRAF V600E mutation in tumor specimens prior to initiation of treatment with TAFINLAR and trametinib [see Clinical Studies (14.7)]. An FDA-approved test for the detection of BRAF V600E mutation in LGG is not currently available.

2.2 Recommended Dosage

TAFINLAR Capsules

Adult Patients

​The recommended dosage for TAFINLAR capsules in adult patients is 150 mg taken orally twice daily [see Dosage and Administration (2.3)].

Pediatric Patients

​The recommended dosage for TAFINLAR capsules in pediatric patients who weigh at least 26 kg is based on body weight (Table 1) [see Dosage and Administration (2.3)]. A recommended dosage of TAFINLAR capsules has not been established in patients who weigh less than 26 kg.

Table 1. Recommended Dosage for TAFINLAR Capsules in Pediatric Patients (Weight-based)

Body Weight	Recommended Dosage
26 to 37 kg	75 mg orally twice daily
38 to 50 kg	100 mg orally twice daily
51 kg or greater	150 mg orally twice daily

TAFINLAR Tablets for Oral Suspension

​The recommended dosage for TAFINLAR tablets for oral suspension is based on body weight (Table 2) [see Dosage and Administration (2.3)].

Table 2. Recommended Dosage for TAFINLAR Tablets for Oral Suspension (Weight-based)

Body Weight	Recommended Dosage
8 to 9 kg	20 mg twice daily
10 to 13 kg	30 mg twice daily
14 to 17 kg	40 mg twice daily
18 to 21 kg	50 mg twice daily
22 to 25 kg	60 mg twice daily
26 to 29 kg	70 mg twice daily
30 to 33 kg	80 mg twice daily
34 to 37 kg	90 mg twice daily
38 to 41 kg	100 mg twice daily
42 to 45 kg	110 mg twice daily
46 to 50 kg	130 mg twice daily
≥ 51 kg	150 mg twice daily

• ​The recommended duration of treatment for patients with unresectable or metastatic melanoma or solid tumors, metastatic NSCLC, or locally advanced or metastatic anaplastic thyroid cancer is until disease progression or unacceptable toxicity.
• ​The recommended duration of treatment in the adjuvant melanoma setting is until disease recurrence or unacceptable toxicity for up to 1 year.
• ​ The recommended duration of treatment for pediatric patients with LGG is until disease progression or until unacceptable toxicity.

Refer to the trametinib prescribing information for recommended trametinib dosing information.