Trodelvy (sacituzumab govitecan-hziy)

P2, N=38, Not yet recruiting, Tianjin Medical University Cancer Institute and Hospital

Key recommendations included: mandatory biopsy at metastasis with ER/PgR/HER2 retesting, HER2-low assessment, and molecular profiling (BRCA, PIK3CA, AKT1/PTEN, ESR1, plus PD-L1 testing in mTNBC); for HR+/HER2- mBC, first-line endocrine therapy plus CDK4/6 inhibitor, followed by targeted agents, chemotherapy, or antibody-drug conjugates based on progression and visceral crisis; for mTNBC, first-line immune checkpoint inhibitor plus chemotherapy in PD-L1-positive, PARP inhibitors in BRCA-positive patients, and sacituzumab-govitecan or trastuzumab-deruxtecan later; systematic toxicity monitoring; and integrated supportive and palliative care. Sixty-one oncologists completed the survey, with >90% overall agreement, suggesting broad acceptance of recommendations as Romania's national standard for mBC care.

Enfortumab vedotin, sacituzumab govitecan, and HER2-directed ADCs have demonstrated meaningful clinical activity across metastatic and earlier disease settings, with enfortumab vedotin plus pembrolizumab now established as a first-line standard of care. We discuss emerging biomarkers beyond antigen abundance, patterns of cross-resistance and treatment sequencing, and evolving strategies to overcome resistance, including next-generation ADC design and rational combination therapies. Advancing biomarker-driven patient selection and addressing mechanisms of resistance will be critical to maximizing the durability and clinical impact of ADCs in urothelial carcinoma.

P2, N=28, Active, not recruiting, Adrienne G. Waks | Recruiting --> Active, not recruiting | N=40 --> 28

P2, N=15, Active, not recruiting, University of Kansas Medical Center | Recruiting --> Active, not recruiting | N=22 --> 15 | Trial primary completion date: Nov 2025 --> Mar 2026

Conventional antibody-based modalities, including antibody-drug conjugates (e.g., sacituzumab govitecan against TROP2) and checkpoint inhibitors (e.g., atezolizumab for programmed death-ligand 1 [PD-L1]), leverage antibody-dependent cellular cytotoxicity, direct antigen blockade, and immune activation to combat tumor growth and evasion...Peptides, such as cell-penetrating variants and vaccines (e.g., HER2-derived AE37), disrupt oncogenic pathways, enable precise drug delivery via conjugates, and elicit antigen-specific immune responses. Aptamers provide high-affinity binding to antigens like nucleolin (e.g., AS1411), supporting targeted delivery and tumor microenvironment modulation. Together, these platforms hold strong potential to overcome chemoresistance, enable subtype-specific treatment personalization, and improve outcomes through synergistic combinations, advancing precision oncology in TNBC.

P2, N=40, Recruiting, Adrienne G. Waks | Trial primary completion date: Nov 2026 --> Feb 2026

With the recent FDA-approval of sacituzumab govitecan and datopotamab deruxtecan in breast cancer, TROP2-targeting therapies showed promising clinical outcomes. This work represents only analytic validation, but work on clinical validation has begun. In the future, this assay may help identify patients who are more likely to benefit from TROP2-targeted therapies.

P1/2, N=50, Not yet recruiting, AIO-Studien gGmbH

P1/2, N=62, Not yet recruiting, Fondazione IRCCS Istituto Nazionale Dei Tumori

P1/2, N=260, Not yet recruiting, Unicancer

P2, N=50, Active, not recruiting, Yale University | Trial completion date: Feb 2026 --> Feb 2027 | Trial primary completion date: Dec 2025 --> Dec 2026