Last updated: June 25, 2026
Trodelvy (sacituzumab govitecan, IMMU-132, sacituzumab govitecan-hziy) is the first FDA-approved TROP2 (trophoblast cell-surface antigen 2)-directed antibody-drug conjugate (ADC). It was originally developed by Immunomedics and is now part of Gilead Sciences (following Gilead's September 2020 acquisition of Immunomedics). Sacituzumab govitecan combines the hRS7 humanized anti-TROP2 IgG1 antibody with a hydrolyzable CL2A linker and SN-38 (the active metabolite of irinotecan, a topoisomerase I inhibitor) at a high drug-to-antibody ratio (DAR ~7.6). The hydrolyzable linker enables a documented bystander effect, killing neighboring TROP2-low cancer cells via membrane-permeable SN-38. Dosed by IV infusion days 1 and 8 of a 21-day cycle.
Mechanism of action:After the antibody binds TROP2 on the cancer cell surface, the ADC-TROP2 complex is internalized into the cell. The hydrolyzable CL2A linker is cleaved, releasing SN-38 inside the cancer cell. SN-38 is a potent topoisomerase I inhibitor (the active metabolite of irinotecan, several hundred-fold more potent than irinotecan itself) that causes single-strand DNA breaks during replication, leading to apoptosis. Because the linker is hydrolyzable in the tumor microenvironment, free SN-38 can also diffuse out of dying cells and enter neighboring TROP2-low cells — the so-called bystander effect, which expands tumor killing beyond TROP2-high cells. See the TROP2 ADCs mechanism hub for the broader class context.
Regulatory status:FDA-approved in 2 active indications as of April 2025: metastatic triple-negative breast cancer 2L+ (ASCENT Phase 3, regular full approval April 2021, replacing the April 2020 accelerated single-arm IMMU-132-01 approval) and HR+/HER2-low or HER2-negative locally advanced or metastatic breast cancer 2L+ after endocrine therapy (TROPiCS-02 Phase 3, February 2023). A third indication — locally advanced or metastatic urothelial cancer (accelerated approval April 2021, TROPHY-U-01) — was voluntarily withdrawn by Gilead in April 2025 after the confirmatory TROPiCS-04 Phase 3 trial missed its primary overall-survival endpoint.
TROP2 (trophoblast cell-surface antigen 2, also known as TACSTD2) is a small protein that sits on the surface of many epithelial cancer cells. Approximately 80-90% of breast, lung, urothelial, cervical, endometrial, ovarian, gastric, and pancreatic adenocarcinomas express TROP2 at high levels, while normal epithelial cells express it at much lower levels. That difference creates a therapeutic window — if a drug can attach itself to TROP2 specifically, it can deliver a payload to cancer cells while sparing most normal tissue.
An antibody-drug conjugate (ADC) is the engineering solution. It is a three-part molecule: a monoclonal antibody that binds a tumor-cell surface marker (like TROP2), a chemical linker, and a cytotoxic payload (typically a chemotherapy that is too toxic to give as a free drug). The antibody acts like a homing missile, the linker is the warhead casing, and the payload is the warhead itself. When the antibody binds TROP2, the cancer cell pulls the whole molecule inside, the linker breaks, and the payload is released to kill the cancer cell from within.
Trodelvy (sacituzumab govitecan) was the first TROP2-directed ADC to receive FDA approval. Its payload is SN-38, the active metabolite of irinotecan — a topoisomerase I inhibitor that you may recognize from colorectal cancer regimens like FOLFIRI. SN-38 is roughly 100-1000 times more potent than its parent drug irinotecan, but in its free form it is too toxic for IV use; the ADC architecture lets oncologists harness that potency with directed delivery. Sacituzumab govitecan also has a high drug-to-antibody ratio (DAR ~7.6) — meaning each antibody carries about 7-8 SN-38 molecules, more than most ADCs. And its hydrolyzable linker creates a bystander effect: SN-38 released from a dying TROP2-positive cell can drift to neighboring cells, including some that don't express TROP2 themselves, broadening the tumor-killing reach.
Because TROP2 is broadly expressed, the FDA label does not currently require TROP2 IHC testing for eligibility — the drug is approved by cancer type, not by a TROP2 expression cutoff. That makes Trodelvy more broadly accessible than tumor markers like HER2 that require companion-diagnostic testing.
Trodelvy currently has 2 active FDA approvals, both in breast cancer. A third approval (urothelial cancer) was voluntarily withdrawn by Gilead in April 2025 after the confirmatory Phase 3 trial missed its primary endpoint.
Metastatic triple-negative breast cancer (mTNBC), 2L+ after at least two prior systemic therapies (at least one for metastatic disease)
HR+/HER2-low or HER2-negative locally advanced or metastatic breast cancer, after endocrine therapy and at least two prior chemotherapies in the metastatic setting
WITHDRAWN APR 2025 — Locally advanced or metastatic urothelial cancer (mUC), 2L+ after platinum chemotherapy and PD-1/PD-L1 inhibitor
★ Trodelvy's clinical position: first-in-class TROP2 ADC + broad cancer-type access (no TROP2 IHC required)
Trodelvy was the first TROP2 ADC to receive FDA approval, and as a result it has the deepest real-world clinical experience, the longest follow-up data, and the most extensively characterized adverse-event profile of any TROP2 ADC. The hydrolyzable linker and high DAR (~7.6) drive a documented bystander effect on TROP2-low neighboring cells, broadening tumor coverage. The FDA label does not require TROP2 IHC testing for eligibility — patients are eligible based on cancer type and prior-therapy criteria alone. This contrasts with HER2 ADCs (which require HER2 IHC/ISH) and many other targeted therapies, and makes Trodelvy more accessible to community-oncology workflows.
For HR+/HER2-low or HER2-negative metastatic breast cancer, both Trodelvy and Datroway (datopotamab deruxtecan, FDA Jan 2025) are FDA-approved options — see the side-by-side comparison below.
Both Trodelvy (sacituzumab govitecan, Gilead) and Datroway (datopotamab deruxtecan, AstraZeneca/Daiichi Sankyo) are FDA-approved TROP2 ADCs — they target the same antigen but use different payload chemistry, linker design, and DAR, leading to distinct toxicity profiles. The choice between them in HR+/HER2-low or HER2-negative breast cancer is a clinical conversation with the treating oncologist:
Curated subset of recruiting interventional Trodelvy (sacituzumab govitecan) trials in the ClinTrialFinder corpus as of June 25, 2026 (approximately 50 recruiting trials total). Trials are grouped by clinical setting and ordered by phase and significance.
The urothelial FDA approval was voluntarily withdrawn by Gilead in April 2025 after TROPiCS-04 missed its primary endpoint. These investigational trials remain open for patients with urothelial cancer whose oncologist considers SG a reasonable clinical-trial option. Standard 1L urothelial therapy is now enfortumab vedotin (Padcev) + pembrolizumab; ask your oncologist about all current options.
TROP2 is broadly expressed across epithelial cancers, so sacituzumab govitecan is being investigated across many cancer types where TROP2 is highly expressed and current therapy is limited. None of these are FDA-approved indications.
Showing a curated subset of recruiting Trodelvy (sacituzumab govitecan) interventional trials in the ClinTrialFinder corpus as of June 25, 2026 (approximately 50 recruiting + not-yet-recruiting trials total). For the latest list: view all recruiting sacituzumab govitecan trials on ClinicalTrials.gov.
Target: TROP2 (trophoblast cell-surface antigen 2, TACSTD2) on the cancer cell surface. Broadly expressed across most epithelial cancers (~80-90% of breast, lung, urothelial, cervical, endometrial, ovarian, gastric, pancreatic).
Antibody: hRS7, a humanized anti-TROP2 IgG1 monoclonal antibody. Linker: a hydrolyzable CL2A linker — cleaved by hydrolysis in the tumor microenvironment and inside the cell. Payload: SN-38, the active metabolite of irinotecan and a potent topoisomerase I inhibitor (~100-1000x more potent than irinotecan itself); too toxic for IV use as a free drug, but harnessed here via directed ADC delivery. Drug-to-antibody ratio (DAR): high, ~7.6 SN-38 molecules per antibody (most other ADCs are at DAR 4 or below).
Mechanism step-by-step: (1) The hRS7 antibody binds TROP2 on the cancer cell surface. (2) The TROP2-ADC complex is internalized by receptor-mediated endocytosis. (3) The hydrolyzable CL2A linker is cleaved, releasing free SN-38 inside the cell. (4) SN-38 inhibits topoisomerase I during DNA replication, causing single-strand DNA breaks that lead to apoptosis. (5) Because the linker is hydrolyzable, some SN-38 is released extracellularly in the tumor microenvironment as well — the membrane-permeable SN-38 can enter neighboring TROP2-low cancer cells and kill them too. This is the bystander effect, which expands tumor coverage beyond TROP2-high cells.
Class context: Trodelvy is the first-in-class TROP2 ADC. The second FDA-approved TROP2 ADC is Datroway (datopotamab deruxtecan, AstraZeneca/Daiichi Sankyo), FDA-approved January 2025 in HR+/HER2-low or HER2-negative metastatic breast cancer based on TROPION-Breast01. Investigational TROP2 ADCs include sacituzumab tirumotecan (Sac-TMT, MK-2870, Merck/Kelun-Biotech — 17 Phase 3 trials, the largest investigational TROP2 ADC program), izalontamab brengitecan (SKB500, Klus Pharma/BMS), and YL202 (MediLink Therapeutics). See the TROP2 ADCs mechanism hub for the cross-drug comparison.
⚠ FDA Boxed Warning #1: Severe or Life-Threatening Neutropenia
Severe (Grade 3-4) neutropenia is common with sacituzumab govitecan, and febrile neutropenia occurs in approximately 6-7% of patients. G-CSF (granulocyte colony-stimulating factor) prophylactic or supportive use is frequently required. Dose interruption and dose reduction are common. Patients should report any fever (temperature ≥ 38.0 °C / 100.4 °F) immediately to the oncology team and seek urgent medical evaluation — febrile neutropenia is a medical emergency. Patients with UGT1A1*28 homozygous (*28/*28) genotype are at higher risk of severe neutropenia due to reduced SN-38 clearance; UGT1A1 genotyping is increasingly used to guide starting-dose decisions (see below).
⚠ FDA Boxed Warning #2: Severe Diarrhea
Severe diarrhea can occur with sacituzumab govitecan and is related to the SN-38 payload (irinotecan-class). Premedication with anti-diarrheal agents (loperamide) is standard. Patients should monitor stool frequency and consistency, maintain hydration and electrolyte balance, and contact the oncology team for diarrhea that does not respond to loperamide within 24 hours, for diarrhea associated with fever or signs of dehydration, or for any Grade 3-4 diarrhea (\ge 7 stools per day over baseline, requiring hospitalization). Severe cases may require IV hydration and electrolyte replacement.
SN-38 is metabolized by the liver enzyme UGT1A1 (uridine diphosphate glucuronosyltransferase 1A1) via glucuronidation. Patients with the UGT1A1*28 polymorphism (the *28 allele, which is a 7-TA-repeat variant in the promoter) have reduced UGT1A1 activity and clear SN-38 more slowly. Homozygous carriers (the *28/*28 genotype) have substantially reduced clearance and are at higher risk of severe neutropenia and severe diarrhea with sacituzumab govitecan, just as they are with irinotecan.
The UGT1A1*28 polymorphism is found in approximately 10% of people of European ancestry, with higher frequencies in some African and South Asian populations and lower frequencies in East Asian populations (where UGT1A1*6 is the more common reduced-function allele). UGT1A1 genotyping is not strictly required by the FDA label for sacituzumab govitecan but is increasingly used in clinical practice to guide starting-dose decisions, monitoring intensity, and G-CSF prophylaxis. If you are starting sacituzumab govitecan, ask your oncologist whether UGT1A1 testing is appropriate for you — particularly if you are of East Asian, African, Hispanic, or South Asian ancestry, or have a personal or family history of irinotecan intolerance.
What is Trodelvy (sacituzumab govitecan)?
Trodelvy is the brand name for sacituzumab govitecan (IMMU-132, sacituzumab govitecan-hziy), the first FDA-approved TROP2-directed antibody-drug conjugate (ADC). It was originally developed by Immunomedics and is now part of Gilead Sciences (following Gilead's September 2020 acquisition of Immunomedics). Sacituzumab govitecan combines the hRS7 humanized anti-TROP2 IgG1 antibody with a hydrolyzable CL2A linker and SN-38 (the active metabolite of irinotecan, a topoisomerase I inhibitor) as the cytotoxic payload, at a high drug-to-antibody ratio (DAR ~7.6). The hydrolyzable linker enables a documented "bystander effect" on TROP2-low neighboring cancer cells via membrane-permeable SN-38. Sacituzumab govitecan is given by intravenous infusion on days 1 and 8 of a 21-day cycle. Two FDA indications are currently active: metastatic triple-negative breast cancer (mTNBC, full approval April 2021 based on the ASCENT Phase 3 trial) and HR+/HER2-low or HER2-negative locally advanced or metastatic breast cancer (February 2023, based on the TROPiCS-02 Phase 3 trial). A third FDA indication in urothelial cancer (April 2021 accelerated approval, TROPHY-U-01) was voluntarily withdrawn by Gilead in April 2025 after the TROPiCS-04 confirmatory Phase 3 trial missed its primary overall-survival endpoint.
Which patients is Trodelvy currently FDA-approved for?
As of April 2025, Trodelvy (sacituzumab govitecan) is FDA-approved in two active indications, both in breast cancer. First indication (metastatic triple-negative breast cancer, full approval April 2021): adult patients with unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC) who have received two or more prior systemic therapies (at least one for metastatic disease) — based on the ASCENT Phase 3 trial vs treatment of physician's choice, which replaced the April 2020 accelerated single-arm IMMU-132-01 approval. Second indication (HR+/HER2-low or HER2-negative advanced breast cancer, February 2023): adult patients with unresectable locally advanced or metastatic HR-positive, HER2-negative (IHC 0, IHC 1+, or IHC 2+/ISH-) breast cancer who have received endocrine-based therapy and at least two additional systemic therapies in the metastatic setting — based on the TROPiCS-02 Phase 3 trial. The urothelial cancer indication was voluntarily withdrawn by Gilead in April 2025 after the TROPiCS-04 confirmatory Phase 3 missed its primary endpoint. The drug remains FDA-approved for the two breast-cancer indications and continues to be studied in clinical trials across SCLC, NSCLC, mCRC, HNSCC, thyroid, mesothelioma, GBM, cervical, esophageal, and ovarian cancers. TROP2 is broadly expressed across most epithelial cancers, which is why the active investigational pipeline is so wide.
Why was Trodelvy's urothelial cancer approval withdrawn?
Trodelvy (sacituzumab govitecan) received FDA accelerated approval in April 2021 for locally advanced or metastatic urothelial cancer (mUC) after platinum-based chemotherapy and a PD-1/PD-L1 checkpoint inhibitor, based on the TROPHY-U-01 single-arm Phase 2 trial. Under the FDA accelerated-approval framework, this approval was conditional on a confirmatory Phase 3 trial. That confirmatory trial was TROPiCS-04, which randomized patients with locally advanced or metastatic urothelial cancer that had progressed after platinum chemotherapy and a checkpoint inhibitor to sacituzumab govitecan vs treatment of physician's choice. TROPiCS-04 missed its primary endpoint of overall survival — sacituzumab govitecan did not show a statistically significant survival benefit over physician's choice chemotherapy in this setting. In April 2025, Gilead voluntarily withdrew the urothelial cancer indication from the U.S. FDA label. Important framing: this withdrawal does not mean sacituzumab govitecan is unsafe — the drug remains FDA-approved for two breast-cancer indications. What it does mean is that, in the urothelial setting specifically, the confirmatory data did not support continued approval. Patients with locally advanced or metastatic urothelial cancer should ask their oncologist about current FDA-approved options, which include enfortumab vedotin (Padcev) + pembrolizumab as a 1L standard, erdafitinib for FGFR-altered tumors, disitamab vedotin for HER2-expressing tumors, and clinical-trial enrollment in next-generation urothelial ADCs and combinations. Active sacituzumab govitecan urothelial clinical trials (NCT03547973, NCT06682728 adjuvant SG + nivolumab MIBC) remain open for patients whose oncologist considers SG a reasonable clinical-trial option.
What are the main side effects of Trodelvy?
Sacituzumab govitecan carries two FDA Boxed Warnings: (1) severe or life-threatening neutropenia and (2) severe diarrhea. Neutropenia is the dominant hematologic toxicity — severe (Grade 3-4) neutropenia is common, and febrile neutropenia occurs in approximately 6-7% of patients. G-CSF support is frequently required, dose interruptions and reductions are common, and patients should report any fever immediately to the oncology team. Diarrhea is the second Boxed Warning and is related to the SN-38 (irinotecan-class) payload — premedication and supportive care (loperamide, hydration, electrolyte monitoring) are standard. Other common adverse events: nausea and vomiting (premedication is standard), alopecia (hair loss), fatigue, anemia, thrombocytopenia, and infusion-related reactions (typically with the first one or two infusions). UGT1A1 testing and pharmacogenomic dose modification: SN-38 is metabolized by UGT1A1. Patients who are UGT1A1*28 homozygous (*28/*28 genotype) have reduced UGT1A1 activity and clear SN-38 more slowly — they are at higher risk of severe neutropenia. UGT1A1 genotyping is not strictly required by the FDA label but is increasingly used in practice to guide starting-dose decisions and monitoring intensity. Patients of East Asian, African, Hispanic, or South Asian ancestry have higher UGT1A1 reduced-function-allele prevalence — ask your oncologist whether UGT1A1 testing is appropriate before starting sacituzumab govitecan.
How is Trodelvy different from Datroway (datopotamab deruxtecan)?
Both Trodelvy (sacituzumab govitecan, Gilead) and Datroway (datopotamab deruxtecan, AstraZeneca/Daiichi Sankyo) are FDA-approved TROP2-directed ADCs — same target, same general mechanism (internalize, release a topoisomerase I inhibitor payload). But they differ in payload chemistry, linker, DAR, and toxicity profile. Payload: Trodelvy delivers SN-38 (irinotecan metabolite); Datroway delivers DXd (deruxtecan, the exatecan-derivative payload also used in trastuzumab deruxtecan/Enhertu and patritumab deruxtecan/HER3-DXd). Linker: Trodelvy uses a hydrolyzable CL2A linker (releases SN-38 inside and outside the cell, driving the bystander effect); Datroway uses a cleavable tetrapeptide-based linker for intracellular release. DAR: Trodelvy ~7.6 (high); Datroway ~4 (moderate). FDA indications: Trodelvy is approved in metastatic TNBC (Apr 2021, ASCENT) and HR+/HER2-low or HER2-negative advanced breast (Feb 2023, TROPiCS-02); Datroway is approved in HR+/HER2-low or HER2-negative metastatic breast (Jan 2025, TROPION-Breast01). Toxicity profile differs meaningfully: Trodelvy's dominant Grade 3-4 toxicities are neutropenia + diarrhea (both Boxed Warnings); Datroway's distinct safety signals include interstitial lung disease (ILD) / pneumonitis (class effect of DXd ADCs requiring CT monitoring and rapid steroid intervention), stomatitis, and ocular toxicity (dry eye, keratitis). For HR+/HER2-low or HER2-negative breast, both are options — the choice depends on prior chemo exposure, pulmonary history, UGT1A1*28 status (homozygous patients at higher neutropenia risk on Trodelvy), and ocular history. See the TROP2 ADCs mechanism hub for the broader class context.
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