Vepdegestrant

VEPPANU is indicated for the treatment of adults with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative, estrogen receptor-1 (ESR1) -mutated advanced or metastatic breast cancer, as detected by an FDA-authorized test, with disease progression following at least one line of endocrine therapy. VEPPANU is a heterobifunctional protein degrader indicated for the treatment of adults with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative, estrogen receptor-1 ( ESR1) -mutated advanced or metastatic breast cancer, as detected by an FDA-authorized test, with disease progression following at least one line of endocrine therapy.

Vepdegestrant is a heterobifunctional protein degrader that binds to estrogen receptor (ER) and the E3 ligase cereblon (CRBN). This interaction results in the degradation cascade through CRBN-mediated polyubiquitination and degradation of ER by the proteasome, leading to reduction of ER protein levels in breast cancer cells. Vepdegestrant induced degradation of wild-type (WT) and mutant ER, inhibited ER-dependent breast cancer cell line proliferation in vitro and demonstrated antitumor activity in vivo in both WT and mutant ESR1 breast cancer models.

Select patients for treatment with VEPPANU based on the presence of ESR1 mutation. Recommended Dosage: 200 mg orally once daily with food. Interruption, dose reduction, or permanent discontinuation may be required due to adverse reactions.

None. None.

QTc Interval Prolongation: Monitor electrocardiograms (ECGs) and electrolytes prior to initiation of treatment with VEPPANU. Correct hypokalemia and hypomagnesemia prior to and during treatment. Repeat ECGs as clinically indicated. Withhold, reduce dose, or permanently discontinue VEPPANU based on severity. Embryo-Fetal Toxicity: VEPPANU can cause fetal harm. Advise patients of the potential risk to a fetus and to use effective contraception.

The following clinically significant adverse reaction is described elsewhere in the labeling: QTc Interval Prolongation Most common ( > 10%) adverse reactions with VEPPANU, including laboratory abnormalities, were decreased white blood cells, increased AST, musculoskeletal pain, fatigue, decreased hemoglobin, decreased neutrophils, increased ALT, increased alkaline phosphatase, nausea, decreased blood potassium, increased bilirubin, decreased appetite, electrocardiogram QT prolonged, decreased platelets, and constipation.

Strong CYP3A Inhibitors: Avoid concomitant use with strong CYP3A inhibitors. If concomitant use cannot be avoided, reduce VEPPANU dosage. Strong CYP3A Inducers: Avoid concomitant use with strong CYP3A inducers. If concomitant use cannot be avoided, increase VEPPANU dosage. Certain P-gp Substrates: Avoid concomitant use with certain P-gp substrates where minimal increases in concentration may lead to serious adverse reactions. Certain UGT1A9 Substrates: Refer to the Prescribing Information for UGT1A9 substrates where minimal increases in concentration may lead to serious adverse reactions.

Storage Store at 20°C to 25°C (68°F to 77°F). Excursions permitted between 15°C and 30°C (between 59°F and 86°F).