Trodelvy (sacituzumab govitecan-hziy) is the first Trop-2-targeted antibody-drug conjugate (ADC) developed by Gilead Sciences. Trop-2 is a cell-surface glycoprotein that is overexpressed across many solid tumors, including non-small cell lung cancer (NSCLC), breast cancer, and colorectal cancer, making it an attractive therapeutic target. By linking an anti-Trop-2 antibody to the topoisomerase-I inhibitor SN-38, Trodelvy delivers cytotoxic payloads directly to Trop-2 expressing tumor cells.
Since 2020, Trodelvy has received multiple FDA approvals in the United States and is now indicated for third-line treatment of metastatic triple-negative breast cancer (TNBC) and fourth-line treatment of HR+/HER2- metastatic breast cancer.
Breakthroughs in Breast Cancer
Trop-2 is overexpressed in up to 95% of both HR+/HER2- and TNBC subtypes of breast cancer. Breast cancer is the most common malignancy in women worldwide, with approximately 15% of cases classified as TNBC, an aggressive subtype prevalent in younger patients, characterized by poor differentiation, high invasiveness, and an elevated risk of early recurrence and metastasis.
Triple-Negative Breast Cancer (TNBC). In April 2020, the FDA granted accelerated approval for Trodelvy in patients with metastatic TNBC who had previously received at least two systemic therapies. In April 2021, based on the Phase III ASCENT trial, Trodelvy received full approval as the first therapy to demonstrate significant improvements in progression-free survival (PFS) and overall survival (OS) in metastatic TNBC. Specifically, Trodelvy extended median PFS from 1.7 to 4.8 months and median OS from 6.9 to 11.8 months, reducing the risk of death by 49%.[1]
HR+/HER2- Breast Cancer. In February 2023, the FDA approved Trodelvy for patients with HR+/HER2- metastatic breast cancer who had received prior endocrine therapy and at least two lines of systemic treatment. The Phase III TROPiCS-02 study showed a median PFS benefit of 5.5 versus 4.0 months (HR 0.66; 95% CI, 0.53–0.83; p = 0.0003) and a median OS benefit of 14.4 versus 11.2 months (HR 0.79; 95% CI, 0.65–0.96; p = 0.02), making Trodelvy the only Trop-2 ADC with proven survival gains in two distinct metastatic breast-cancer subtypes. [2]
Advances in First-Line Therapy
ASCENT-04 (Trodelvy + Keytruda). In April 2025, Gilead announced the positive topline results from the Phase III ASCENT-04/KEYNOTE-D19 study, demonstrating that Trodelvy® plus Keytruda® (pembrolizumab) achieved its primary endpoint, demonstrating statistically and clinically meaningful PFS improvement versus pembrolizumab plus chemotherapy in patients with inoperable (unresectable) locally advanced or metastatic TNBC whose tumors express PD-L1 (CPS ≥ 10). [3]
On May 31, 2025, at the 2025 ASCO meeting, Gilead announced the results of its Phase III ASCENT-04/KEYNOTE-D19 study, showed that sacituzumab govitecan combined with pembrolizumab significantly improved PFS compared to chemotherapy plus pembrolizumab. Patients receiving the sacituzumab govitecan regimen (n = 221) achieved a median PFS of 11.2 months (95% CI, 9.3–16.7) by blinded independent central review (BICR), versus 7.8 months (95% CI, 7.3–9.3) in the chemotherapy group (n = 222), representing a 35% reduction in the risk of disease progression or death (HR, 0.65; 95% CI, 0.51–0.84; P < .001). The 6- and 12-month PFS rates were also notably higher in the sacituzumab govitecan arm—72% and 48%, respectively—compared to 63% and 33% in the chemotherapy arm. [8]
ASCENT-03 (Trodelvy Monotherapy). In May 2025, Gilead Sciences announced that the Phase III ASCENT-03 trial of Trodelvy® met its primary endpoint, showing a highly statistically significant and clinically meaningful improvement in PFS versus standard chemotherapy in first-line metastatic TNBC patients who are not candidates for PD-1/PD-L1 inhibitors. [4]
Exploring Other Tumor Types: Progress and Challenges
Figure 1. Trodelvy clinical trials, source: Gilead official website
Urothelial Carcinoma (mUC). In April 2021, Trodelvy received accelerated FDA approval for patients with locally advanced or metastatic urothelial carcinoma who had received a platinum-containing chemotherapy and either a PD-1 or a PD-L1 inhibitor. However, the subsequent Phase III TROPiCS-04 confirmatory trial failed to meet overall-survival endpoints and showed higher mortality in the Trodelvy arm. Gilead voluntarily withdrew this indication in October 2024. [5]
Non-Small Cell Lung Cancer (NSCLC). In January 2024, Gilead announced that the Phase 3 EVOKE-01 study did not meet its primary endpoint of overall survival (OS) in previously treated metastatic NSCLC with only a 1.3-month OS extension versus docetaxel (not statistically significant). Yet, exploratory analyses suggest greater benefit in patients unresponsive to prior PD-(L)1 inhibitors. [6]
Extensive-stage Small Cell Lung Cancer (ES-SCLC). Trodelvy has shown promise in ES-SCLC. In 2024, the Phase II TROPiCS-03 study reported a 41.9% objective response rate, a median progression-free survival of 4.4 months, and a median overall survival of 13.6 months in patients whose disease was refractory to first-line chemo-immunotherapy. Based on these results, the FDA granted Trodelvy Breakthrough Therapy Designation in December 2024 for ES-SCLC patients whose disease progressed following platinum-based chemotherapy. [7]
Additional Indications. In July 2024, Gilead launched the Phase III ASCENT-GYN-01 trial in endometrial cancer; early exploratory studies are also underway in gastric and bladder cancers.
Looking Ahead
Despite setbacks in certain indications, Trodelvy’s achievements in breast cancer have laid a solid groundwork for further Trop-2–targeted research. Gilead is actively investigating its use in NSCLC, urothelial carcinoma, gastric cancer, endometrial cancer, and other solid tumors. As additional clinical data become available, Trodelvy could broaden precision-medicine strategies and offer new hope to patients across a range of malignancies.
References:
[1]https://www.gilead.com/news/news-details/2021/fda-approves-trodelvy-the-first-treatment-for-metastatic-triple-negative-breast-cancer-shown-to-improve-progression-free-survival-and-overall-survival
[2]https://www.gilead.com/news/news-details/2023/us-fda-approves-trodelvy-in-pre-treated-hrher2--metastatic-breast-cancer
[3]https://www.gilead.com/news/news-details/2025/trodelvy-plus-keytruda-demonstrates-a-statistically-significant-and-clinically-meaningful-improvement-in-progression-free-survival-in-patients-with-previously-untreated-pd-l1-metastatic-trip
[4]https://www.gilead.com/news/news-details/2025/ascent-03-trodelvy-demonstrates-highly-statistically-significant--clinically-meaningful-improvement-in-progression-free-survival-in-patients-with-first-line-metastatic-triple-negative-breast
[5]https://www.gilead.com/company/company-statements/2024/gilead-provides-update-on-us-indication-for-trodelvy-in-metastatic-urothelial-cancer
[6]https://www.oncologypipeline.com/apexonco/asco-2024-full-evoke-01-result-adds-gileads-trodelvy-problems
[7]https://www.jto.org/article/S1556-0864(24)02549-8/fulltext Phase 2 Open-Label Study of Sacituzumab Govitecan as Second-Line Therapy in Patients With Extensive-Stage SCLC: Results From TROPiCS-03
[8] https://www.asco.org/about-asco/press-center/news-releases/sacituzumab-govitecan-helps-some-patients-with-PD-L1-positive-triple-negative-breast-cancer-live-longer-without-cancer-progression