Sacituzumab govitecan — Drug Monograph

Sacituzumab Govitecan (Trodelvy) — TROP2 ADC Overview

Sacituzumab govitecan (Trodelvy) is a TROP2-directed antibody-drug conjugate (ADC) that delivers the SN-38 topoisomerase I inhibitor payload to TROP2-expressing tumors. It is a mainstay for metastatic triple-negative breast cancer (TNBC), including first-line settings, and is also approved for pretreated HR-positive breast cancer and previously treated urothelial carcinoma. This monograph covers sacituzumab govitecan dosing (10 mg/kg IV on Days 1 and 8 of a 21-day cycle), TROP2 targeting, metastatic TNBC and urothelial carcinoma lines, UGT1A1 genotyping context, and management of severe neutropenia and diarrhea.

Indications (FDA / NCCN)

• First-line metastatic TNBC (monotherapy or + pembrolizumab for PD-L1+; ASCENT-03/04)
• Metastatic TNBC after ≥2 prior systemic therapies (ASCENT)
• HR-positive, HER2-negative breast cancer after endocrine therapy + ≥2 chemo lines
• Locally advanced / metastatic urothelial carcinoma after platinum and a PD-1/PD-L1 inhibitor

Dosing

• Standard dose: 10 mg/kg IV on Days 1 and 8 of a 21-day cycle
• First infusion over 3 h; may shorten to 1–2 h if tolerated
• Premedicate: antiemetic (highly emetogenic), antipyretic, antihistamine
• Hold for ANC <1,500/µL (Day 1) or <1,000/µL (Day 8)

Monitoring

• UGT1A1 genotyping before starting (*28/*28 → higher toxicity, consider dose reduction)
• CBC with differential before each dose; G-CSF support often required
• Diarrhea — early cholinergic (atropine) vs late secretory (high-dose loperamide)
• Hydration and electrolytes for severe diarrhea

Brand names: Trodelvy

Drug class: Antibody-Drug Conjugate

Mechanism of Action

Anti-Trop-2 (trophoblast cell-surface antigen 2) antibody-drug conjugate. Trop-2 is overexpressed on many solid tumors including TNBC, HR+/HER2- breast cancer, and urothelial carcinoma. The humanized anti-Trop-2 IgG1 antibody is conjugated via a cleavable CL2A linker to SN-38 (the active metabolite of irinotecan, a topoisomerase I inhibitor). Drug-to-antibody ratio ~7.6. After internalization and linker cleavage, SN-38 inhibits topoisomerase I, causing DNA double-strand breaks and apoptosis. SN-38 has moderate membrane permeability, enabling a bystander killing effect on adjacent Trop-2-low…

FDA Indications

• Metastatic TNBC — first-line, as monotherapy for patients not eligible for checkpoint inhibitors (ASCENT-03; June 24, 2026)
• Metastatic TNBC — first-line, in combination with pembrolizumab for PD-L1-positive patients (ASCENT-04; June 24, 2026)
• Triple-negative breast cancer (TNBC) — locally advanced or metastatic, after ≥2 prior systemic therapies including ≥1 for metastatic disease (ASCENT trial)
• HR-positive, HER2-negative breast cancer — locally advanced or metastatic, after endocrine therapy and ≥2 prior chemotherapy regimens for metastatic disease
• Locally advanced or metastatic urothelial carcinoma — after prior platinum-containing chemotherapy and PD-1 or PD-L1 inhibitor

Common Side Effects

• Diarrhea (60–65% any grade; late-onset most common)
• Nausea (65%)
• Neutropenia (50–60%)
• Fatigue
• Alopecia
• Anemia
• Vomiting
• Constipation
• Abdominal pain

Clinical Pearl

As of June 24, 2026, sacituzumab govitecan is approved in first-line metastatic TNBC — as monotherapy in PD-L1-negative patients (ASCENT-03; 38% reduction in progression/death vs. chemotherapy) and in combination with pembrolizumab in PD-L1-positive patients (ASCENT-04; 35% reduction), making it the first ADC approved in the front-line TNBC setting. The ASCENT trial established sacituzumab govitecan as standard of care for metastatic TNBC after ≥2 prior lines (median OS 12.1 vs. 6.7 months vs.…

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