LuciDorda (Dordaviprone)

About Dordaviprone

Dordaviprone  is an anti-cancer medication used for the treatment of diffuse midline glioma (a type of brain tumor). Dordaviprone is a protease activator of the mitochondrial caseinolytic protease P. It is dopamine receptor D2 antagonist and an allosteric activator of the mitochondrial caseinolytic protease P.

Dordaviprone is indicated for the treatment of people with diffuse midline glioma harboring an H3 K27M mutation with progressive disease following prior therapy.

Glioma

Indicated for treatment of diffuse midline glioma harboring an H3 K27M mutation in adults with progressive disease following prior therapy

625 mg PO once weekly until disease progression or unacceptable toxicity

Dosage Modifications

Recommended dosage adjustments for treatment-related toxicity

• First reduction: 500 mg PO once weekly
• Second reduction: 375 mg PO once weekly

Hypersensitivity

• Hold therapy until resolution if hypersensitivity is suspected, based on clinical judgement
• Permanently discontinue for serious hypersensitivity reactions

QTc interval prolongation

• QTc increase of >60 milliseconds (msec) from baseline or >500 msec: Hold until QTc interval ≤480 msec or return to baseline; resume therapy at next lower dose level
• Torsades de pointes (TdP), polymorphic ventricular tachycardia, or signs/symptoms of serious or life-threatening arrhythmia: Permanently discontinue

Other adverse reactions

• Grade 3 or 4: Hold until Grade ≤1 or return to baseline; resume therapy at next lower dose level
• Recurrent Grade 4: Permanently discontinue

Recommended dosage adjustments for use with CYP3A4 inhibitors

• Strong CYP3A4 inhibitors

  • Avoid coadministration
  • If concomitant use cannot be avoided, reduce dosage to 375 mg PO once weekly

• Moderate CYP3A4 inhibitors

  • Avoid coadministration
  • If concomitant use cannot be avoided, reduce dosage to 500 mg PO once weekly
• Upon CYP3A4 inhibitor discontinuation, wait 3-5 plasma half-lives of the CYP3A4 inhibitor and then increase dordaviprone back to prior dosage

Renal impairment

• Mild or moderate (CrCl 30-89 mL/min): Not studied
• Severe (CrCl <30 mL/min): Exposure increased by 50% following a single dordaviprone dose that was 0.6x the maximum approved recommended dose (see Pharmacology); however, no initial dosage adjustment is recommended by the manufacturer

Hepatic impairment

• Mild (total bilirubin [TB] ≤ULN with AST >ULN, or TB >1-1.5x ULN with any AST): No significant impact on pharmacokinetics compared with normal hepatic function
• Moderate (Child Pugh class B): Exposure increased by 50% following a single dordaviprone dose that was 0.2x the maximum approved recommended dose (see Pharmacology); however, no initial dosage adjustment is recommended by the manufacture
• Severe (TB >3x ULN with any AST): Not studied