ROS1-positive non-small cell lung cancer

Active Ingredient: Repotrectinib

Indication for Repotrectinib

Population group: only adults (18 years old or older)
Therapeutic intent: Curative procedure

Repotrectinib is indicated for the treatment of adult patients with locally advanced or metastatic ROS1-positive non-small cell lung cancer (NSCLC).

For this indication, competent medicine agencies globally authorize below treatments:

160 mg once daily for 14 days and thereafter 160 mg twice daily until disease progression or unacceptable toxicity

For:

Dosage regimens

Oral, 160 milligrams repotrectinib, once daily, over the duration of 14 days. Afterwards, oral, 160 milligrams repotrectinib, 2 times daily.

Detailed description

Select patients for the treatment of locally advanced or metastatic NSCLC with repotrectinib based on the presence of ROS1 rearrangement(s) in tumor specimens.

Important information prior to initiating repotrectinib

Prior to initiating repotrectinib, discontinue strong and moderate CYP3A inhibitors for 3 to 5 elimination half-lives of the CYP3A inhibitor.

Recommended evaluation and testing before initiating repotrectinib

Prior to initiation of repotrectinib, evaluate:

  • liver function tests including bilirubin
  • uric acid level

Recommended dosage

The recommended dosage of repotrectinib is 160 mg taken orally once daily with or without food for 14 days, then increase to 160 mg twice daily and continue until disease progression or unacceptable toxicity.

Dosage modifications for adverse reactions

The recommended dosage reductions of repotrectinib for the management of adverse reactions are provided in Table 1.

Table 1. Recommended dose reductions for repotrectinib adverse reactions:

Dose Dose Reduction
First Second
160 mg Once Daily 120 mg Once Daily 80 mg Once Daily
160 mg Twice Daily 120 mg Twice Daily 80 mg Twice Daily

Recommended dosage modifications of repotrectinib for the management of adverse reactions are provided in Table 2.

Table 2. Recommended dosage modifications for repotrectinib adverse reactions:

Adverse Reaction Severity* Dosage Modification
Central Nervous System
Effects
Intolerable
Grade 2
• Withhold repotrectinib until ≤Grade 1 or
baseline.
• Resume at same or reduced dose, as
clinically appropriate.
Grade 3 • Withhold repotrectinib until ≤Grade 1 or
baseline.
• Resume at reduced dose.
Grade 4 • Permanently discontinue repotrectinib.
Interstitial Lung Disease
(ILD)/Pneumonitis
Any Grade • Withhold repotrectinib if ILD/pneumonitis
is suspected.
• Permanently discontinue if
ILD/pneumonitis is confirmed.
Hepatotoxicity Grade 3 • Withhold repotrectinib until ≤Grade 1
or baseline.
• Resume at same dose if resolution occurs
within 4 weeks.
• Resume at a reduced dose for recurrent
Grade 3 events that resolve within
4 weeks.
Grade 4 • Withhold repotrectinib until ≤Grade 1
or baseline.
• Resume at reduced dose.
• Permanently discontinue if adverse
reaction does not resolve within 4 weeks.
• Permanently discontinue for recurrent
Grade 4 events.
ALT or AST
greater than 3
times ULN
with
concurrent
total bilirubin
greater than
1.5 times
ULN (in the
absence of
cholestasis or
hemolysis)
• Permanently discontinue repotrectinib.
Creatine Phosphokinase
(CPK) Elevation
CPK
elevation
greater than 5
times ULN
• Withhold until recovery to baseline or to
less than or equal to 2.5 times ULN, then
resume at same dose.
CPK
elevation
greater than
10 times ULN
or second
occurrence of
CPK
elevation of
greater than 5
times ULN
• Withhold until recovery to baseline or to
less than or equal to 2.5 times ULN, then
resume at reduced dose.
Hyperuricemia Grade 3 or
Grade 4
• Withhold repotrectinib until improvement
of signs or symptoms.
• Resume repotrectinib at same or reduced
dose.
Other Clinically Relevant
Adverse Reactions
Intolerable
Grade 2 or
Grade 3 or
Grade 4
• Withhold repotrectinib until ≤Grade 1
or baseline.
• Resume at the same or reduced dose if
resolution occurs within 4 weeks.
• Permanently discontinue if adverse
reaction does not resolve within 4 weeks.
• Permanently discontinue for recurrent
Grade 4 events.

* Graded per Common Terminology Criteria for Adverse Events v4.03

Dosage considerations

Take repotrectinib at approximately the same time each day with or without food.

If a dose of repotrectinib is missed or if vomiting occurs at any time after taking a dose, skip the dose and resume repotrectinib at its regularly scheduled time.

Active ingredient

Repotrectinib

Repotrectinib is an inhibitor of proto-oncogene tyrosine-protein kinase ROS1 (ROS1) and of the tropomyosin receptor tyrosine kinases (TRKs) TRKA, TRKB, and TRKC. Fusion proteins that include ROS1 domains can drive tumorigenic potential through hyperactivation of downstream signaling pathways leading to unconstrained cell proliferation. Repotrectinib exhibited anti-tumor activity in cultured cells expressing ROS1 fusions and mutations including SDC4-ROS1, SDC4-ROS1G2032R, CD74-ROS1, CD74-ROS1G2032R, CD74-ROS1D2033N, and CD74-ROS1L2026M.

Read more about Repotrectinib

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