Vepdegestrant
What it isVepdegestrant (ARV-471) is an investigational oral PROTAC that recruits an E3 ubiquitin ligase to drive proteasomal degradation of the estrogen receptor.
Why this oneIt is being developed for ER-positive/HER2-negative advanced breast cancer, with the Phase 3 VERITAC-2 trial showing improved progression-free survival versus fulvestrant in ESR1-mutant patients.
What limits itIt is not yet FDA approved, and its monotherapy benefit was confined to the ESR1-mutant subgroup rather than the overall population.
FDA-approved for
- ESR1-mutated ER+/HER2- advanced breast cancer (2026)
FDA label
Read the full label on DailyMed ↗
| FDA dosing | Population | Start | Target | Max |
|---|---|---|---|---|
| ER-positive, HER2-negative advanced or metastatic breast cancer, ESR1-mutated (FDA-authorized plasma test) | Adults | 200 mg QD with food | 200 mg QD until progression or unacceptable toxicity | 200 mg QD |
Renal Undefined
Hepatic Undefined
Avoid strong CYP3A inhibitors and inducers; if unavoidable at 200 mg QD: reduce to 100 mg QD (inhibitor) or increase to 300 mg QD (inducer), then resume 200 mg QD after washout
Instructions
- Take with food; swallow whole - do not chew, crush, dissolve, or split; do not use broken/cracked/damaged tablets
- Missed dose or vomiting after a dose: skip; take next dose at the regularly scheduled time
- Select patients by ESR1 mutation in plasma using an FDA-authorized test
- ECG and electrolytes before initiation (do not initiate if QTc >470 ms); correct hypokalemia/hypomagnesemia; repeat ECG ~4 weeks after starting and as indicated
- Adverse-reaction dose reduction: 100 mg QD; permanently discontinue if 100 mg QD not tolerated
- QTc >480 ms or >60 ms above baseline: withhold until resolved, then resume per label; permanently discontinue for recurrent QTc >500 ms or torsade/serious arrhythmia
Cautions
- QTc prolongation: baseline and on-treatment ECG/electrolyte monitoring; do not initiate if QTc >470 ms; extra monitoring with congenital long QT syndrome, CHF, electrolyte abnormalities, or QT-prolonging drugs
- Embryo-fetal toxicity: verify pregnancy status before starting; effective contraception (females and males with female partners) during treatment and for 2 weeks after last dose
Adverse reactions
- Decreased WBC/neutrophils/hemoglobin/platelets; increased AST/ALT/ALP/bilirubin; decreased potassium
- Musculoskeletal pain (30%), fatigue (29%), nausea, constipation, decreased appetite
- ECG QT prolonged (10%; Grade 3 in 1.6%)
Pregnancy Can cause fetal harm (embryo-fetal mortality and structural abnormalities in rats below human exposure); verify pregnancy status before initiation
Lactation Do not breastfeed during treatment and for 2 weeks after last dose
NO BOXED WARNINGS
Principal riskNo FDA boxed warning (investigational).
Classes and tags
Clinical profile
Mechanism of action: Vepdegestrant ballicule
