RETEVMO

RETEVMO- selpercatinib capsule
Eli Lilly and Company

1 INDICATIONS AND USAGE

​1.1 RET Fusion-Positive Non-Small Cell Lung Cancer

​RETEVMO^® is indicated for the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with a rearranged during transfection (RET) gene fusion, as detected by an FDA-approved test.

1.2 RET -Mutant Medullary Thyroid Cancer

​RETEVMO is indicated for the treatment of adult and pediatric patients 12 years of age and older with advanced or metastatic medullary thyroid cancer (MTC) with a RET mutation, as detected by an FDA-approved test, who require systemic therapy.

This indication is approved under accelerated approval based on overall response rate and duration of response [see Clinical Studies (14.2)]. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).

1.3 RET Fusion-Positive Thyroid Cancer

​RETEVMO is indicated for the treatment of adult and pediatric patients 12 years of age and older with advanced or metastatic thyroid cancer with a RET gene fusion, as detected by an FDA-approved test, who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate).

This indication is approved under accelerated approval based on overall response rate and duration of response [see Clinical Studies (14.3)]. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).

​1.4 Other RET Fusion-Positive Solid Tumors

​RETEVMO is indicated for the treatment of adult patients with locally advanced or metastatic solid tumors with a RET gene fusion that have progressed on or following prior systemic treatment or who have no satisfactory alternative treatment options.

​This indication is approved under accelerated approval based on overall response rate and duration of response [see Clinical Studies (14.4)]. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).

2 DOSAGE AND ADMINISTRATION

2.1 Patient Selection

​Select patients for treatment with RETEVMO based on the presence of a RET gene fusion (NSCLC, thyroid cancer, or other solid tumors) or specific RET gene mutation (MTC) in tumor specimens [see Clinical Studies (14)]. Information on FDA-approved test(s) for the detection of RET gene fusions and RET gene mutations is available at: http://www.fda.gov/CompanionDiagnostics. An FDA-approved companion diagnostic test for the detection of RET gene fusions and RET gene mutations in plasma or in tumors other than NSCLC and thyroid cancer is not currently available.

2.2 Important Administration Instructions

RETEVMO may be taken with or without food unless coadministered with a proton pump inhibitor (PPI) [see Dosage and Administration (2.4), Clinical Pharmacology (12.3)].

2.3 Recommended Dosage

The recommended dosage of RETEVMO based on body weight is:

• Less than 50 kg: 120 mg
• 50 kg or greater: 160 mg

Take RETEVMO orally twice daily (approximately every 12 hours) until disease progression or unacceptable toxicity.

Swallow the capsules whole. Do not crush or chew the capsules.

Do not take a missed dose unless it is more than 6 hours until next scheduled dose.

If vomiting occurs after RETEVMO administration, do not take an additional dose and continue to the next scheduled time for the next dose.

2.4 Dosage Modifications for Concomitant Use of Acid-Reducing Agents

Avoid concomitant use of a PPI, a histamine-2 (H2) receptor antagonist, or a locally-acting antacid with RETEVMO [see Drug Interactions (7.1)]. If concomitant use cannot be avoided:

• Take RETEVMO with food when coadministered with a PPI.
• Take RETEVMO 2 hours before or 10 hours after administration of an H2 receptor antagonist.
• Take RETEVMO 2 hours before or 2 hours after administration of a locally-acting antacid.

2.5 Dosage Modifications for Adverse Reactions

The recommended dose reductions for adverse reactions are provided in Table 1.

Table 1: Recommended RETEVMO Dose Reductions for Adverse Reactions

Dose Reduction	Patients WeighingLess Than 50 kg	Patients Weighing50 kg or Greater
First	80 mg orally twice daily	120 mg orally twice daily
Second	40 mg orally twice daily	80 mg orally twice daily
Third	40 mg orally once daily	40 mg orally twice daily

Permanently discontinue RETEVMO in patients unable to tolerate three dose reductions.

The recommended dosage modifications for adverse reactions are provided in Table 2.

Table 2: Recommended RETEVMO Dosage Modifications for Adverse Reactions

Adverse Reaction	Severity	Dosage Modification
Hepatotoxicity[see Warnings and Precautions (5.1)]	Grade 3orGrade 4	Withhold RETEVMO and monitor AST/ALT once weekly until resolution to Grade 1 or baseline. Resume at reduced dose by 2 dose levels and monitor AST and ALT once weekly until 4 weeks after reaching dose taken prior to the onset of Grade 3 or 4 increased AST or ALT. Increase dose by 1 dose level after a minimum of 2 weeks without recurrence and then increase to dose taken prior to the onset of Grade 3 or 4 increased AST or ALT after a minimum of 4 weeks without recurrence.
​Interstitial Lung Disease/ Pneumonitis[see Warnings and Precautions (5.2)]	Grade 2	Withhold RETEVMO until resolution. Resume at a reduced dose. Discontinue RETEVMO for recurrent ILD/pneumonitis.
	Grade 3 orGrade 4	Discontinue RETEVMO for confirmed ILD/pneumonitis.
Hypertension[see Warnings and Precautions (5.3)]	Grade 3	Withhold RETEVMO for Grade 3 hypertension that persists despite optimal antihypertensive therapy. Resume at a reduced dose when hypertension is controlled.
	Grade 4	Discontinue RETEVMO.
QT Interval Prolongation[see Warnings and Precautions (5.4)]	Grade 3	Withhold RETEVMO until recovery to baseline or Grade 0 or 1. Resume at a reduced dose.
	Grade 4	Discontinue RETEVMO.
Hemorrhagic Events[see Warnings and Precautions (5.5)]	Grade 3orGrade 4	Withhold RETEVMO until recovery to baseline or Grade 0 or 1. Discontinue RETEVMO for severe or life-threatening hemorrhagic events.
Hypersensitivity Reactions[see Warnings and Precautions (5.6)]	All Grades	Withhold RETEVMO until resolution of the event. Initiate corticosteroids. Resume at a reduced dose by 3 dose levels while continuing corticosteroids. Increase dose by 1 dose level each week until the dose taken prior to the onset of hypersensitivity is reached, then taper corticosteroids.
​Hypothyroidism[see Warnings and Precautions (5.9)]	Grade 3 orGrade 4	Withhold RETEVMO until resolution to Grade 1 or baseline. Discontinue RETEVMO based on severity.
Other Adverse Reactions[see Adverse Reactions (6.1)]	Grade 3orGrade 4	Withhold RETEVMO until recovery to baseline or Grade 0 or 1. Resume at a reduced dose.