P2, N=36, Not yet recruiting, Sichuan Baili Pharmaceutical Co., Ltd.

P3, N=700, Recruiting, AbbVie | Not yet recruiting --> Recruiting

Antibody-drug conjugates (ADCs), such as trastuzumab deruxtecan (T-DXd) and sacituzumab govitecan (SG) offer new and potent options for curing for curing hormone receptor-positive (HR+)/human epidermal growth factor receptor 2 (HER2)-low advanced breast cancer; however, comparisons in terms of their relative effectiveness and safety concerns are lacking. Compared with other ADC drugs, T-DXd showed relatively better treatment characteristics, better PFS benefit, and relatively low incidence of serious AEs (SAEs). Combined with RCTs and real-world data, T-DXd has potential advantages in this population.

Postoperatively, he received adjuvant stereotactic radiosurgery (30-35 Gy in five fractions) to the resection cavity and was transitioned from tamoxifen to trastuzumab deruxtecan (T-DXd) for improved CNS-directed systemic therapy. Surveillance imaging at 6 months demonstrated no intracranial recurrence, and systemic restaging showed no extracranial disease progression. This case highlights the importance of prompt neuroimaging for new neurological symptoms in male breast cancer patients and supports a multimodal strategy, including surgical resection, focal radiation, and CNS-penetrant HER2-targeted therapy, for achieving durable intracranial control in select patients with isolated brain metastasis.

Three ADCs are currently approved for previously treated gynaecological cancers: mirvetuximab soravtansine for folate receptor-α-positive ovarian cancer, trastuzumab deruxtecan for solid tumours expressing HER2 (defined as a staining intensity on immunohistochemistry of 3+) and tisotumab vedotin for cervical cancer (independent of tissue factor expression). Moreover, rational combinations could reinforce and extend the clinical potential of these agents, as has already been demonstrated with the addition of ADCs to immune checkpoint inhibitors in an effort to amplify antitumour immunity and prolong the durability of clinical responses. In this Review, we provide an overview of the current landscape of ADCs in gynaecological malignancies, highlighting key advances and future opportunities.

P1, N=152, Active, not recruiting, AbbVie | Recruiting --> Active, not recruiting | N=230 --> 152

ADCs against TROP2 (Sacituzumab govitecan) or HER2 (T-DXd) have demonstrated efficacy in metastatic breast cancer, yet paradoxically, outside of HER2-amplified breast cancers, expression levels of these breast cancer-enriched epitopes in tumor biopsies have not been strongly correlated with clinical response. Thus, while CTC burden is correlated with response to these ADCs, the level of TROP2 or HER2 expression is poorly predictive. These findings point to sensitivity to the drug payload as a potential driver of clinical response to currently approved ADCs in breast cancer.

P2, N=124, Recruiting, The First Affiliated Hospital of Soochow University

P3, N=440, Recruiting, MediLink Therapeutics (Suzhou) Co., Ltd. | Not yet recruiting --> Recruiting

P3, N=1630, Recruiting, Eli Lilly and Company | N=1080 --> 1630 | Trial primary completion date: Apr 2028 --> Nov 2028

With the expanding use of trastuzumab deruxtecan (T-DXd), sacituzumab govitecan (SG), and datopotamab deruxtecan (Dato-DXd) across HER2-positive, HER2-low, and hormone-receptor-positive disease, management of treatment-related toxicities has become a critical determinant of outcomes. Integrating these findings, we propose practical algorithms for managing pulmonary, gastrointestinal, hematologic, ocular, and mucosal adverse events. This review consolidates evidence into a clinician-oriented reference for ADC toxicity management, emphasizing multidisciplinary coordination, early recognition, and system-specific mitigation strategies to enhance treatment safety and adherence.