Overview
11. DESCRIPTION Pivekimab sunirine-pvzy is a CD123-directed antibody and alkylating agent conjugate created by conjugating the IgG1 monoclonal antibody G4723A to the DGN549C linker-payload. The antibody-drug conjugate (ADC) contains approximately two DGN549C molecules sulfonated prior to conjugation and bound to the heavy chains (HC) of the G4723A antibody.
Mechanism of Action
12. CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Pivekimab sunirine-pvzy is a CD123 (alpha-subunit of the interleukin-3 receptor)-directed antibody-drug conjugate (ADC). The antibody is a humanized anti-CD123 IgG1. Pivekimab sunirine-pvzy binds to CD123 expressing cells and upon intracellular processing releases a cell membrane-permeable payload, FGN849, leading to DNA alkylation, single-strand DNA breaks, apoptosis, and cell death. The payload, FGN849, is a member of the indolinobenzodiazepine pseudodimer (IGN) class of cytotoxic molecules. Pivekimab sunirine-pvzy exhibited antitumor activity in in vitro and in vivo models of BPDCN. 12.
Indications
- 1. INDICATIONS AND USAGE DECNUPAZ is indicated for the treatment of adult patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN). DECNUPAZ is a CD123-directed antibody and alkylating agent conjugate indicated for the treatment of adult patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN). ( 1 )
Common Doses
- 0.045 mg
- 8 mg
- 25 mg
- 50 mg
Dosage
2. DOSAGE AND ADMINISTRATION For intravenous infusion only. ( 2.6 ) The recommended dose of DECNUPAZ is 0.045 mg/kg once every 3 weeks until disease progression or unacceptable toxicity. ( 2.2 ) Premedicate with a corticosteroid on the day prior to infusion and premedicate with a corticosteroid, antihistamine, and an antipyretic at least 30 to 60 minutes prior to DECNUPAZ infusion. ( 2.3 ) DECNUPAZ requires reconstitution followed by two dilutions prior to administration. See full Prescribing Information for instructions on preparation and administration. ( 2.5 , 2.6 ) 2.
Black Box Warning
WARNING: HEPATOTOXICITY, INCLUDING HEPATIC VENO-OCCLUSIVE DISEASE (VOD) (ALSO KNOWN AS SINUSOIDAL OBSTRUCTION SYNDROME) DECNUPAZ can cause hepatotoxicity, including severe or fatal hepatic VOD (also known as sinusoidal obstruction syndrome) [see Warnings and Precautions ( 5.1 )] . Closely monitor patients for signs and symptoms of VOD including elevations in liver tests, hepatomegaly (which may be painful), rapid weight gain, and ascites [see Warnings and Precautions ( 5.1 )] .
Contraindications
- 4. CONTRAINDICATIONS None. None. ( 4 )
Side Effects
- 6. ADVERSE REACTIONS The following clinically significant adverse reactions are discussed elsewhere in the labeling: Hepatotoxicity, Including Hepatic VOD (also known as Sinusoidal Obstruction Syndrome) [see Warnings and Precautions ( 5.1 )] Infusion-Related Reactions [see Warnings and Precautions ( 5.2 )] Edema [see Warnings and Precautions ( 5.3 )] The most common adverse reactions (≥20%) were edema, fatigue, musculoskeletal pain, hemorrhage, infusion-related reactions, nausea, and diarrhea. ( 6.
Interactions
- 7. DRUG INTERACTIONS Strong and M oderate CYP3A Inhibitors : Closely monitor for DECNUPAZ adverse reactions ( 7.1 ) 7.1 Effect of Other Drugs on DECNUPAZ Strong and moderate CYP3A inhibitors Closely monitor patients for adverse reactions with DECNUPAZ when used concomitantly with strong and moderate CYP3A inhibitors. FGN849 is a substrate of CYP3A [see Clinical Pharmacology ( 12.3 )] . Concomitant use of DECNUPAZ with strong and moderate CYP3A inhibitors may increase unconjugated FGN849 exposure, which may increase the risk of DECNUPAZ adverse reactions.