Progress of Trop-2-targeted antibody-drug conjugates in HER-2-negative breast cancer: a mini-review

Breast cancer (BC) persists as a major cause of deaths associated with cancer among women globally, emphasizing the necessity for innovative therapeutic approaches (1). In 2022, the global data from GLOBOCAN, indicated that BC represented approximately 2.3 million new cases, accounting for 11.6% of all cancer diagnoses (2). At the global level, China reported the highest number of newly diagnosed BC cases (N=357,161) in females (3). Among women, it made up nearly 25% of cancer cases and nearly 16% of cancer-related deaths (2). It is a diverse disease characterized by multiple molecular subtypes, such as hormone receptor-positive (HR+), human epidermal growth factor receptor 2-positive (HER2+) BC and triple-negative breast cancer (TNBC) (1).

Trophoblast cell surface antigen 2 (Trop-2) is a membrane-bound glycoprotein that promotes tumor growth, cell proliferation, and metastasis by regulating calcium signaling, cyclin expression, and decreasing adhesion to extracellular matrix proteins (1). In 2010, Trop-2 was identified to promote tumorigenesis through activation of the extracellular signal-regulated kinase/mitogen-activated protein kinase pathways, marking the start of functional research into its role in cancer (4). Higher levels Trop-2 expression are observed in many solid tumors and correlated with poor prognosis (5). Notably, it is present in >90% of TNBC cases, making it a compelling therapeutic target.

Antibody-drug conjugates (ADCs) integrate the potent cytotoxic properties of chemotherapy with the precise antigen-targeting ability of antibodies within a single molecule. ADCs primarily consist of 3 key structural components: a monoclonal antibody, a cytotoxic agent (“payload” or “warhead”), and a linker. They selectively bind to tumor cell surface antigens, internalized by the tumor cells, thereby releasing cytotoxic drugs inside the cells through enzymatic or chemical linker degradation, leading to apoptosis in the tumor cells. Some ADCs demonstrate a “bystander effect”, where released drugs diffuse into nearby cancer cells regardless of target antigen specificity, and promotes cell death. This mechanism enhances the therapeutic effect and reduces the drug resistance caused by tumor heterogeneity (5).

In the Phase 3 ASCENT trial, sacituzumab govitecan (SG), an ADC targeting Trop-2 demonstrated significant improvement in survival outcomes in patients with advanced TNBC (6). Compared with traditional chemotherapy, Trop-2-targeted ADCs improve the effectiveness and minimize the safety issues by selectively delivering cytotoxic agents to tumor cells with Trop-2 expression (1). Trop-2 ADCs are promising anticancer agents. Multiple studies have confirmed their reliable efficacy and safety in patients with refractory and metastatic breast cancer (mBC). They have also demonstrated remarkable efficacy in various malignancies such as lung cancer and gynecological tumors (7-10).

This article reviews the progress of Trop-2 ADCs in treating TNBC and HR+/HER2− BC, and summarizes the relevant clinical trials on Trop-2-targeted ADCs for the treatment for these 2 subtypes, and discusses their applications and future prospects.

Three major Trop-2 ADCs have been globally investigated for treating advanced TNBC and HR+/HER2− BC: SG, datopotamab deruxtecan (Dato-DXd), and sacituzumab tirumotecan (SKB264).Among them, SG has obtained approval from both the National Medical Products Administration (NMPA) and United States Food and Drug Administration (FDA) for TNBC and HR+/HER2− BC treatment (11). SKB264 is only approved in China for TNBC (12), whereas Dato-DXd is approved in the United States for HR+/HER2− BC (13), but has not yet been approved in China. Figure 1 summarizes the composition of the 3 major ADCs: SG, SKB264, and Dato-DXd.

Figure 1 Major third-generation Trop-2 ADCs. ADC, antibody-drug conjugate; IgG, immunoglobulin G; Trop-2, trophoblast cell surface antigen 2.

SG

SG is the first FDA-approved Trop-2-targeting ADC for the treatment of advanced TNBC and HR+/HER2− BC (11). It consists of a humanized anti-Trop-2 IgG1 kappa antibody, sacituzumab (hRS7), conjugated to the topoisomerase I inhibitor, 7-ethyl-10-hydroxycamptothecin (SN-38), via a cleavable linker (CL2A) with a high drug-to-antibody ratio (DAR: 7.6). Following administration, the anti-Trop-2 monoclonal antibody binds to Trop-2 expressed on tumor cells, facilitating the targeted delivery of SN-38 to these cells. This precise drug delivery minimizes damage to healthy cells (1,5). This mechanism of action suggests that SG may prolong progression-free survival (PFS) and overall survival (OS) in the treatment of TNBC and HR+/HER2− BC.

The first Phase 1/2 study IMMU-132-01 (NCT01631552) evaluated the efficacy of SG in the treatment of advanced epithelial cancers, including TNBC, HR+/HER2−BC, lung cancer, and urothelial cancer. The efficacy data of the TNBC vs. HR+/HER2− cohorts were as follows: objective response rate (ORR; 33.3% vs. 31.5%), clinical benefit rate (CBR; 45.4% vs. 44.4%), median duration of response (mDoR; 9.1 vs. 8.7 months), median progression-free survival (mPFS; 5.6 vs. 5.5 months), and median overall survival (mOS; 13.0 vs. 12 months) (14). These findings further led to the preliminary validation of the efficacy and safety of SG in BC.

The ASCENT study (NCT02574455) is the first Phase 3 clinical trial of SG. In this study, patients with metastatic TNBC (mTNBC) who had received a median of 4 lines of prior systemic therapy achieved an mPFS of 5.6 months [95% confidence interval (CI): 4.3–6.3] with SG and 1.7 months (95% CI: 1.5–2.6) with single-agent chemotherapy of the physician’s choice (eribulin, vinorelbine, capecitabine, or gemcitabine). The mOS was 12.1 months (95% CI: 10.7–14.0) in the SG group and 6.7 months (95% CI: 5.8–7.7) in the chemotherapy group. The treatment-related adverse events (TRAEs) of grade ≥3 reported in both the groups, respectively, were neutropenia (51% vs. 33%), leukopenia (10% vs. 5%), diarrhea (10% vs. <1%), anemia (8% vs. 5%), and febrile neutropenia (6% vs. 2%) (8). A Phase 2b, multicenter, single-arm study (EVER-132-001; NCT04454437) (15) involving Chinese patients with mTNBC who had received a median of 4 lines of prior systemic therapy reported an mPFS of 5.6 months (95% CI: 4.1–8.3), and the mOS was 14.7 months (95% CI: 10.3–18.3). In this trial, SG consistently showed a significant clinical efficacy and demonstrated improvements in ORR (40%), duration of response (DoR; 11.6 months; 95% CI: 7.0–13.8), CBR (46%), and median time to response (TTR; 1.6 months; range: 1.2–4.2 months). SG demonstrated efficacy across patient subgroups and consistent safety profile with previous study of SG (8). Based on the clinical findings, treatment guidelines from National Comprehensive Cancer Network, European Society for Medical Oncology, Chinese Society of Clinical Oncology, and Chinese Anti-Cancer Association recommend SG as a preferred choice for the second-line treatment of mTNBC. In the phase 3 ASCENT-03 trial (NCT05382299) (16), in previously untreated advanced TNBC, including patients who were PD-L1 negative or ineligible for immunotherapy, SG improved BICR-assessed PFS, compared to physician’s-choice chemotherapy [9.7 vs. 6.9 months; hazard ratio (HR): 0.62; 95% CI: 0.50–0.77; P<0.001] and demonstrated a prolonged DoR (12.2 vs. 7.2 months), with a similar ORR (48% vs. 46%). After confirmed progression, a protocol-specified crossover allowed the chemotherapy-arm to receive SG (82% of those receiving subsequent therapy). Although OS was immature at the primary PFS analysis, PFS2 numerically favoured SG (18.2 vs. 14.0 months), supporting SG benefit in first-line therapy.

In a Phase 3 TROPiCS-02 trial (NCT03901339) (10) involving patients with confirmed HR+ and HER2− locally recurrent inoperable or mBC who received at least 1 prior endocrine therapy, a taxane, a CDK4/6 inhibitor, and 2 to 4 prior chemotherapies. SG demonstrated median improvement of 1.5 months in PFS (5.5 vs. 4.0 months) with a 35% reduction in risk of progression or death. The mOS was 14.4 months (95% CI: 13.0–15.7) in the SG group and 11.2 months (95% CI: 10.1–12.7) in the chemotherapy group; the HR was 0.79 (95% CI: 0.65–0.96; P=0.020), with a median follow-up of 12.5 months [interquartile range (IQR): 6.4–18.8 months]. In the EVER-132-002 Phase 3 study (17) involving Asian patients with HR+ and HER2− mBC, SG reduced the risk of disease progression or recurrence by 33% compared with the chemotherapy group (HR: 0.67; 95% CI: 0.52–0.87; P=0.0028). The OS was also improved with a median of 21.0 vs. 15.3 months (HR: 0.64; 95% CI: 0.47–0.88; P=0.0061). SG demonstrated safety outcomes similar to those observed in previous research (8,10). These findings suggest SG as a new promising therapeutic strategy for patients with pretreated, endocrine-resistant HR+ and HER2– mBC.

Overall, SG has proven to be highly effective in the treatment of both TNBC and HR+/HER2− BC with a manageable safety profile. It demonstrated clinically meaningful improvement over chemotherapy and provides a valuable therapeutic option for patients. The major ongoing clinical trials on SG for the treatment of BC are summarized in Table 1.

Dato-DXd

Dato-DXd is composed of a humanized anti-Trop-2 IgG1 antibody, a cleavable peptide linker, and the topoisomerase I inhibitor exatecan mesylate (DXd). It has a half-life of ~45.1±13.9 hours with an average DAR of 4.

TROPION-Breast01 (NCT05104866) (18) was a global phase 3 trial including patients with HR+/HER2− mBC, and who received 1–2 prior lines of therapy. Dato-DXd significantly improved PFS vs. investigator’s choice of chemotherapy (BICR-assessed HR: 0.63; 95% CI: 0.52–0.76; P<0.0001), with similar benefit observed across subgroups, while OS data remain immature (HR: 0.84; 95% CI: 0.62–1.14). Grade ≥3 TRAEs were less frequent with Dato-DXd (20.8% vs. 44.7%). Commonly observed any-grade TRAEs with Dato-DXd included nausea (51.1%) and stomatitis (50%), while neutropenia predominated with chemotherapy (42.5%). Ocular toxicity (mostly dry eye) occurred in 40% of patients receiving Dato-DXd, and leading to one treatment discontinuation.

TROPION-Breast02 trial (NCT05374512) (19) demonstrated that first-line Dato-DXd significantly improved mPFS (10.8 vs. 5.6 months; HR: 0.57; 95% CI: 0.47–0.69; P<0.001) and mOS (23.7 vs. 18.7 months; HR: 0.79; 95% CI: 0.64–0.98; P=0.0291) compared with investigator’s choice of chemotherapy in patients with unresectable or mTNBC who were ineligible for immunotherapy. Overall, Dato-DXd significantly improved the PFS and demonstrated anti-tumor activity in patients with HER2− advanced BC. TRAEs reported were mostly mild and manageable, indicating a favorable safety and tolerability profile. Currently ongoing studies on Dato-DXd are summarized in Table S1.

SKB264

SKB264 is also a Trop-2-targeted ADC that selectively binds to Trop-2-positive cells by targeting the Trop-2 protein expressed on the cell surface and thereby inducing endocytosis (9). It uses the same humanized antibody (hRS7) as SG (1) and used a cleavable linker with 2-(methylsulfonyl) pyrimidine to attach the topoisomerase I inhibitor T030 (a belotecan derivative), and has a DAR of 7.4.

OptiTROP-Breast01 (NCT05347134) (20), a Phase 3 study of SKB264/MK-2870 involving patients with mTNBC who had received a median of 3 lines of prior systemic therapy, demonstrated an mPFS of 5.7 months (95% CI: 4.3–7.2) with SKB264, compared with 2.3 months (95% CI: 1.6–2.7) with chemotherapy. The mOS was not reached with SKB264 (95% CI: 11.2–not available), whereas it was 9.4 months (95% CI: 8.5–11.7) with chemotherapy. The most commonly reported grade ≥3 TRAEs (SKB264 vs. chemotherapy) were decreased neutrophil count (32.3% vs. 47.0%), anemia (27.7% vs. 6.1%), and decreased white blood cell count (25.4% vs. 36.4%).

The phase 3 OptiTROP-Breast02 trial (NCT06081959) (21) demonstrated significantly improved PFS (8.3 vs. 4.1 months; HR: 0.35; P<0.0001) and ORR (41.5% vs. 24.1%) of SKB264, compared to physician’s choice of chemotherapy in Chinese patients with heavily pretreated HR+/HER2− mBC, with a favorable safety profile. SKB264 also showed consistent benefit across HER2 expression subgroups. These results suggest that SKB264 exhibited an efficacy and safety profile in patients with pretreated HR+/HER2− mBC, similar to observations made in patients with TNBC. A comprehensive list of ongoing clinical trials is listed in Table S2.

Trop-2 ADCs in early stage and residual disease settings

Although Trop-2 ADCs have primarily demonstrated efficacy in the mBC setting, several pivotal clinical trials are now exploring their role in earlier stage disease, particularly in patients with residual invasive disease following neoadjuvant chemotherapy, a population known to have a high risk of recurrence (Table S3).

The phase III studies, ASCENT-05 (NCT05633654) (22) evaluating SG + pembrolizumab, TROPION-Breast03 (NCT05629585) (23) assessing Dato-DXd as both monotherapy and combined with durvalumab, and TroFuse-012 (NCT06393374) (24) examining SKB264 + pembrolizumab, together assess if ADC mono or ADC-immunotherapy combinations can further reduce recurrence risk after incomplete response to neoadjuvant therapy.

Other Trop-2 ADCs under development

To date, approximately >150 other Trop-2-targeted ADCs are under investigation in distinct types of cancers including BC (25). In the Phase 1a, ESG-401 (NCT04892342) study (26), ESG-401 exhibited a promising efficacy in patients with the subtypes of BC. The ORR was 47.0% (8/17) for patients with HR+/HER2− BC and 29.4% (5/17) for TNBC, respectively. In addition, several novel Trop-2 ADCs (e.g., ESG-401, YL202, LCB84, and SHR-A1921) targeting TNBC and HR+/HER2− BC have shown their potential in phase 1–3 trials. Currently ongoing trials on other Trop-2 ADCs are listed in Table S4.

Drug combination strategies for Trop-2 ADCs

Owing to the heterogeneity of malignant tumors and individual variability, single-agent therapy often fails to achieve ideal outcomes. Therefore, exploring combination drug strategies has become a hotspot in anti-tumor research. Currently, multiple combination regimens involving Trop-2 ADCs are being explored in the field of BC. Among these, the most highly anticipated combination therapies primarily focus on the synergistic application of Trop-2 ADCs with immunotherapies or poly (ADP-ribose) polymerase (PARP) inhibitors. Related studies are actively underway, aiming to further enhance the antitumor efficacy through mechanistic complementarity.

Trop-2 ADCs enhance immune surveillance by re-programming macrophages, activating dendritic and T cells, boosting the effectiveness of immune checkpoint inhibitors (ICIs), and optimizing the tumor microenvironment (TME) (1). Clinical studies are progressively investigating combination therapies that integrate Trop-2-targeted ADCs with ICIs, such as anti-PD-1/PD-L1, aiming to boost antitumor responses and expanding therapeutic benefits.

In the MORPHEUS-panBC study (NCT03424005) (27), patients with previously untreated PD-L1+ inoperable locally advanced/mTNBC, received a combination of atezolizumab (atezo), a PD-L1 inhibitor and SG. The outcomes of atezo + SG combination compared with atezo + nanoparticle albumin-bound paclitaxel (nab-P) showed an ORR (76.7% vs. 66.7%), a CBR (83.3% vs. 66.7%), and an mPFS (12.2 vs. 5.9 months), with a median follow-up duration (10.6 vs. 11.7 months). Atezo combined with SG showed safety outcomes similar to those of the individual agents, and no new safety signals were reported. In arm 7 of the BEGONIA study (NCT03742102) (28), Dato-DXd combined with durvalumab (an anti-PD-L1 antibody) as a first-line novel therapy demonstrated durable response rates and tolerable safety in patients with advanced or mTNBC. These findings suggest that combining Trop-2-targeted ADCs with ICIs holds a significant potential to enhance therapeutic outcomes in patients with advanced cancers.

The Phase 3 ASCENT-04/KEYNOTE-D19 (NCT05382286) study in patients with first-line, locally advanced, unresectable PD-L1-positive mTNBC demonstrating that the combination of SG and pembrolizumab provides clinically meaningful survival benefits over chemotherapy plus pembrolizumab with the mPFS (11.2 vs. 7.8 months; HR: 0.65; 95% CI: 0.51–0.84), ORR (60% vs. 53%), mDoR (16.5 vs. 9.2 months) (29). The ASCENT-03/04 trials have established a new paradigm for first-line therapy in the entire population of patients with advanced TNBC.

ADCs with topoisomerase I inhibitors can work synergistically with PARP inhibitors to more effectively suppress the proliferation of BC tumor cells (1). In the Phase 1b SEASTAR study (30), patients with metastatic solid tumors including TNBC, endothelial cancer, ovarian cancer, and urothelial cancer were treated with the combination of rucaparib and SG regardless of homologous recombination repair gene mutation status. Although the combination showed promising efficacy, dose-limiting toxicities such as absolute neutrophil count decline and neutropenia-related adverse events were observed, attributed to the known overlapping toxicities of topoisomerase I and PARP inhibitors. This highlights the need to optimize dosing regimens to mitigate toxicity. Sequential therapy has emerged as a potential strategy to address these challenges. A recent study evaluating the sequential administration of SG and talazoparib demonstrated safety and efficacy in mTNBC, with an mPFS of 6.2 months, mOS of 18 months, ORR of 30.1%, and 6-month CBR of 53.8%. Grade ≥3 TRAEs reported in patients were neutropenia (80.7%) and anemia (34.6%). These findings may offer a promising avenue for future investigation (31).

Brain metastases represent a severe complication affecting approximately 15% to 25% of patients with stage IV BC. The treatment for brain metastasis is challenging because of several factors including restrictive blood-brain barrier, molecular heterogeneity, an immunosuppressive TME, and the morbidity associated with brain, highlighting the need for effective treatments that can achieve meaningful disease control (32,33).

The TUXEDO-2 trial, evaluating the effectiveness and safety of Dato-DXd in TNBC patients with active brain metastases reported an intracranial response rate of 37.5% (32). Treatment was well tolerated, and no new safety signals were identified.

In a Phase 0 window-of-opportunity study (33), SG was found to have good tolerability, sufficient penetration into intracranial tumors, and favorable preliminary central nervous system activity in patients with breast cancer brain metastases (BCBM) and recurrent glioblastoma (rGBM). The OS was 35.2 months in patients with BCBM and 9.5 months in those with rGBM. Notably, the exploratory analysis showed Trop-2 expression in 100% of BCBM tumors and in 78% of rGBM tumors, supporting further investigation of Trop-2-targeted ADCs in central nervous system malignancies.

Clinical implications of Trop-2 ADCs in the mBC settings

The first line landscape of mTNBC depends on PD-L1 expression status.

ASCENT-04 supports SG as a promising option for PD-L1-positive population, while ASCENT-03 and TROPION Breast02 provide effective chemotherapy free Trop-2 targeted options for PD L1-negative or immunotherapy ineligible patients. Selection between these Trop-2 ADCs ultimately depends on their distinct safety profiles and individual patient’s tolerability.

In metastatic HR+/HER2– disease, choosing between Dato-DXd and SG requires balancing survival data, toxicity profiles, and dosing schedules. SG showed definitive PFS and OS benefits in TROPiCS-02, whereas Dato-DXd did not demonstrate a significant OS improvement in TROPION-Breast01. Therefore, treatment should be individualized by considering SG’s proven OS benefit, and the distinct safety profiles (stomatitis and ILD with Dato DXd vs. myelosuppression and diarrhea with SG), and practical dosing convenience of both ADCs.

Sequencing considerations for Trop-2 ADCs

Evidence on the optimal sequencing of Trop-2 ADCs and its associated clinical outcomes in mBC remain limited. A systematic review of 23 studies suggests that switching ADC payloads may reduce cross-resistance and improve ORR and PFS2 compared to same-payload sequences. Treatment decisions should consider payload type, timing, BC subtype, and toxicity profiles. Further research on resistance mechanisms and biomarkers is needed to guide personalized sequencing strategies (34).

Future research directions should focus on the following aspects: first, Trop-2 is known for its intricate oligomerization and interactions with other proteins. The relationship between Trop-2 oligomer assembly and its biological functions remains unclear, and its interaction mechanisms with molecular partners are yet to be fully elucidated. Notably, Trop-2 is expressed on both tumor cells and some non-malignant tissues, potentially causing inevitable on-target and off-target toxicities. Efforts to evaluate Trop-2 epitopes, investigate its interaction kinetics, and understand its biology will facilitate the development of more precise and effective novel therapies. Second, the lack of standardized quantification methods to measure Trop-2 expression introduces inaccuracies in the selection of patient for clinical trials, which could affect the integrity of study results. A biomarker-driven approach to Trop-2 testing should be adopted as the standard strategy in clinical studies to enhance patient selection and therapeutic outcomes. Third, innovations in ADC designs may improve antibody internalization, tumor specificity, payload release, and stability. Furthermore, as the data on long-term efficacy and safety of Trop-2 ADCs are limited, several novel drugs are under development and being investigated. Optimizing combination therapies for Trop-2 ADCs is also currently being explored, including combination with ICIs, PARP inhibitors, or antiangiogenic drugs and other targeted drugs. It should be noted that the additive toxicity from drug interactions may increase the risk of treatment failure, highlighting the need to find the optimal combination therapy with good response and manageable toxicity. In addition, the downstream pathway of Trop-2 and combination therapy modalities to reverse drug resistance must be explored more.

In conclusion, the advancement of antitumor drugs targeting Trop-2 holds considerable importance. At present, several Trop-2 ADC therapies have made breakthroughs and received approvals for use in the treatment of TNBC and HR+/HER2− BC. Trop-2 ADCs have made significant progress in BC therapy; however, many challenges remain, which require further investigations. Overall, SG is highly effective in treating both TNBC and HR+/HER2− BC with a manageable safety profile and a clinically meaningful improvement over chemotherapy, thereby providing a valuable therapeutic option for patients.

Acknowledgments

None.

Footnote

Peer Review File: Available at https://tbcr.amegroups.com/article/view/10.21037/tbcr-2025-1-79/prf

Funding: None.

Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at https://tbcr.amegroups.com/article/view/10.21037/tbcr-2025-1-79/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Tong Y, Fan X, Liu H, et al. Advances in Trop-2 targeted antibody-drug conjugates for breast cancer: mechanisms, clinical applications, and future directions. Front Immunol 2024;15:1495675. [Crossref] [PubMed]
2. Bray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2024;74:229-63. [Crossref] [PubMed]
3. Cancer Today [Internet]. 2025. Available online: https://gco.iarc.who.int/today/
4. Cubas R, Zhang S, Li M, et al. Trop2 expression contributes to tumor pathogenesis by activating the ERK MAPK pathway. Mol Cancer 2010;9:253. [Crossref] [PubMed]
5. Shastry M, Jacob S, Rugo HS, et al. Antibody-drug conjugates targeting TROP-2: Clinical development in metastatic breast cancer. Breast 2022;66:169-77. [Crossref] [PubMed]
6. Bardia A, Tolaney SM, Punie K, et al. Biomarker analyses in the phase III ASCENT study of sacituzumab govitecan versus chemotherapy in patients with metastatic triple-negative breast cancer. Ann Oncol 2021;32:1148-56. [Crossref] [PubMed]
7. Alhalabi O, Lisberg A, Drakaki A, et al. Datopotamab deruxtecan (Dato-DXd) in locally advanced/metastatic urothelial cancer: Updated results from the phase 1 TROPIONPanTumor01 study. J Clin Oncol 2025;43.
8. Bardia A, Hurvitz SA, Tolaney SM, et al. Sacituzumab Govitecan in Metastatic Triple-Negative Breast Cancer. N Engl J Med 2021;384:1529-41. [Crossref] [PubMed]
9. Cheng Y, Yuan X, Tian Q, et al. Preclinical profiles of SKB264, a novel anti-TROP2 antibody conjugated to topoisomerase inhibitor, demonstrated promising antitumor efficacy compared to IMMU-132. Front Oncol 2022;12:951589. [Crossref] [PubMed]
10. Rugo HS, Bardia A, Marmé F, et al. Overall survival with sacituzumab govitecan in hormone receptor-positive and human epidermal growth factor receptor 2-negative metastatic breast cancer (TROPiCS-02): a randomised, open-label, multicentre, phase 3 trial. Lancet 2023;402:1423-33. [Crossref] [PubMed]
11. PRESCRIBING INFORMATION- TRODELVY® (sacituzumab govitecan-hziy) for injection, for intravenous use Initial U.S. Approval: 2020 [Internet]. Available online: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761115s035lbl.pdf
12. Sacituzumab Tirumotecan Earns Approval in China in Pretreated Advanced TNBC-OncoDaily [Internet]. 2024 Nov 30. Available online: https://oncodaily.com/drugs/sacituzumab-193201
13. FDA approves datopotamab deruxtecan-dlnk for unresectable or metastatic, HR-positive, HER2-negative breast cancer. FDA [Internet]. 2025. Available online: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-datopotamab-deruxtecan-dlnk-unresectable-or-metastatic-hr-positive-her2-negative-breast
14. Bardia A, Messersmith WA, Kio EA, et al. Sacituzumab govitecan, a Trop-2-directed antibody-drug conjugate, for patients with epithelial cancer: final safety and efficacy results from the phase I/II IMMU-132-01 basket trial. Ann Oncol 2021;32:746-56. [Crossref] [PubMed]
15. Ma F, Wang S, Tong Z, et al. Abstract PO1-06-10: Overall survival results from EVER-132-001, a phase 2b single-arm study of sacituzumab govitecan in Chinese patients with metastatic triple-negative breast cancer. Cancer Res 2024;84:PO1-06-10.
16. Cortés J, Punie K, Barrios C, et al. Sacituzumab Govitecan in Untreated, Advanced Triple-Negative Breast Cancer. N Engl J Med 2025;393:1912-25. [Crossref] [PubMed]
17. Xu B, Wang S, Yan M, et al. Sacituzumab govitecan in HR+HER2- metastatic breast cancer: the randomized phase 3 EVER-132-002 trial. Nat Med 2024;30:3709-16. [Crossref] [PubMed]
18. Bardia A, Jhaveri K, Im SA, et al. Datopotamab Deruxtecan Versus Chemotherapy in Previously Treated Inoperable/Metastatic Hormone Receptor-Positive Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer: Primary Results From TROPION-Breast01. J Clin Oncol 2025;43:285-96. [Crossref] [PubMed]
19. Dent RA, Shao Z, Schmid P, et al. LBA21 First-line (1L) datopotamab deruxtecan (Dato-DXd) vs. chemotherapy in patients with locally recurrent inoperable or metastatic triple-negative breast cancer (mTNBC) for whom immunotherapy was not an option: Primary results from the randomised, phase 3 TROPION-Breast02 trial. ESMO Congr 2025.
20. Xu B, Yin Y, Fan Y, et al. Sacituzumab tirumotecan (SKB264/MK-2870) in patients (pts) with previously treated locally recurrent or metastatic triple-negative breast cancer (TNBC): Results from the phase III OptiTROP-Breast01 study. J Clin Oncol 2024;42:104.
21. Fan Y, Li H, Wang H, et al. LBA23 Sacituzumab tirumotecan (sac-TMT) vs. investigator’s choice of chemotherapy (ICC) in previously treated locally advanced or metastatic hormone receptor-positive, HER2-negative (HR+/HER2-) breast cancer (BC): Results from the randomized, multi-center phase III OptiTROP-Breast02 study. ESMO Congr 2025.
22. Gilead Sciences. Study of Sacituzumab Govitecan-hziy and Pembrolizumab Versus Treatment of Physician's Choice in Patients With Triple Negative Breast Cancer Who Have Residual Invasive Disease After Surgery and Neoadjuvant Therapy (ASCENT-05/AFT-65 OptimICE-RD/GBG 119/NSABP B-63) [Clinical trial registration] [Internet]. clinicaltrials.gov; 2026 Jan [cited 2026 Feb 25]. Report No.: NCT05633654. Available online: https://clinicaltrials.gov/study/NCT05633654
23. AstraZeneca. A Study of Dato-DXd Versus Investigator's Choice Chemotherapy in Patients With Locally Recurrent Inoperable or Metastatic Triple-negative Breast Cancer, Who Are Not Candidates for PD-1/PD-L1 Inhibitor Therapy (TROPION-Breast02) [Clinical trial registration] [Internet]. clinicaltrials.gov; 2026 Jan [cited 2026 Feb 25]. Report No.: NCT05374512. Available online: https://clinicaltrials.gov/study/NCT05374512
24. Merck Sharp & Dohme LLC. Sacituzumab Tirumotecan (MK-2870) Plus Pembrolizumab Versus TPC in TNBC Who Did Not Achieve pCR (MK-2870-012) [Clinical trial registration] [Internet]. clinicaltrials.gov; 2026 Feb [cited 2026 Mar 3]. Report No.: NCT06393374. Available online: https://clinicaltrials.gov/study/NCT06393374
25. Li N, Yang L, Zhao Z, et al. Antibody-drug conjugates in breast cancer: current evidence and future directions. Exp Hematol Oncol 2025;14:41. [Crossref] [PubMed]
26. Wang J, Tong Z, Tan Y, et al. Phase 1a study of ESG401, a Trop2 antibody-drug conjugate, in patients with locally advanced/metastatic solid tumors. Cell Rep Med 2024;5:101707. [Crossref] [PubMed]
27. Schmid P, Loi S. 181O Interim analysis (IA) of the atezolizumab (atezo) + sacituzumab govitecan (SG) arm in patients (pts) with triple-negative breast cancer (TNBC) in MORPHEUS-pan BC: A phase Ib/II study of multiple treatment (tx) combinations in pts with locally advanced/metastatic BC (LA/mBC). ESMO Open 2024;9.
28. Schmid P, Wysocki PJ, Ma CX, et al. 379MO Datopotamab deruxtecan (Dato-DXd) + durvalumab (D) as first-line (1L) treatment for unresectable locally advanced/metastatic triple-negative breast cancer (a/mTNBC): Updated results from BEGONIA, a phase Ib/II study. Ann Oncol 2023;34:S337.
29. Tolaney SM, de Azambuja E, Kalinsky K, et al. Sacituzumab govitecan (SG) + pembrolizumab (pembro) vs. chemotherapy (chemo) + pembro in previously untreated PD-L1-positive advanced triple-negative breast cancer (TNBC): Primary results from the randomized phase 3 ASCENT-04/ KEYNOTE-D19 study. J Clin Oncol 2025;43:abstr LBA109.
30. Yap TA, Hamilton E, Bauer T, et al. Phase Ib SEASTAR Study: Combining Rucaparib and Sacituzumab Govitecan in Patients With Cancer With or Without Mutations in Homologous Recombination Repair Genes. JCO Precis Oncol 2022;6:e2100456. [Crossref] [PubMed]
31. Spring L, Niemierko A, Abraham E, McNeice M, Goff J, Valenti A, et al. Sequential combination of sacituzumab govitecan and talazoparib in metastatic triple negative breast cancer (mTNBC): Results from a phase II study. J Clin Oncol. 2024;42:
32. Bartsch R, Berghoff AS, Furtner J, et al. 187P Stage I results of a phase II study of datopotamab deruxtecan (DATO-DXd) in triple-negative breast cancer (TNBC) patients (pts) with active brain metastases (TUXEDO-2). ESMO Open 2024;9.
33. Balinda HU, Kelly WJ, Kaklamani VG, et al. Sacituzumab Govitecan in patients with breast cancer brain metastases and recurrent glioblastoma: a phase 0 window-of-opportunity trial. Nat Commun 2024;15:6707. [Crossref] [PubMed]
34. de Almeida LFC, Leite LF, Cappellaro AP, et al. Sequencing antibody-drug conjugates in metastatic breast cancer: A systematic review. Cancer Treat Rev 2026;142:103067. [Crossref] [PubMed]