Trodelvy (sacituzumab govitecan-hziy)

P1/2, N=1132, Recruiting, Hoffmann-La Roche | N=792 --> 1132

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.

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.

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.

Conventional chemotherapy and first-generation antibody-drug conjugates (ADCs), such as ado-trastuzumab emtansine (T-DM1), were limited by non-specific cytotoxicity, heterogeneous drug-antibody ratios, linker instability, and insufficient bystander killing, yielding modest efficacy in heavily pretreated populations...Clinically, trastuzumab deruxtecan demonstrated meaningful progression-free survival benefit in HER2-low metastatic breast cancer, while enfortumab vedotin reduced mortality risk in platinum- and immunotherapy-refractory urothelial carcinoma, establishing ADC efficacy across solid tumor histologies...Trastuzumab deruxtecan carries a 15.4% incidence of interstitial lung disease, including fatal events, and sacituzumab govitecan is associated with grade 3 or higher neutropenia in approximately 51% of patients. Furthermore, next-generation ADCs are not resistance-proof, with antigen downregulation, payload efflux, and impaired internalization emerging as clinically relevant escape mechanisms. Biomarker-driven patient selection, rigorous toxicity monitoring, and prospective trials addressing resistance will be essential to realizing the full and durable potential of this drug class.

P=N/A, N=60, Recruiting, Regina Elena Cancer Institute | Trial completion date: Jun 2025 --> Jun 2027

In multivariable analysis, Eastern Cooperative Oncology Group (ECOG) performance status was the only independent predictor of poorer survival (hazard ratio 1.97, 95% CI 1.42-2.74, p < 0.01), while gBRCA1/2 status showed no independent association. In this large retrospective cohort of mTNBC patients treated with SG, the presence of gBRCA1/2 was not associated with statistically significant differences in PFS or OS.

P2, N=192, Active, not recruiting, Gilead Sciences | Recruiting --> Active, not recruiting

Late-phase ADCs include trastuzumab deruxtecan (targeting HER2 [human epidermal growth factor receptor 2]), datopotamab deruxtecan and sacituzumab govitecan (targeting TROP2 [trophoblast cell-surface antigen 2]), patritumab deruxtecan (targeting HER3), telisotuzumab vedotin (targeting c-MET [cellular-mesenchymal epithelial transition factor]), and sigvotatug vedotin (targeting IB6 [integrin beta-6]). Ongoing, biomarker-driven trials and combination strategies with immunotherapy or tyrosine kinase inhibitors hold the potential to further enhance the efficacy of ADCs. In this review, the authors highlight the current landscape and future directions of ADCs in NSCLC, emphasizing available results for compounds in late-stage clinical development and different disease settings.

Although Osimertinib was initiated as first-line therapy based on the identified EGFR exon 21 L858R mutations, the patient experienced disease progression. Subsequent treatment with ivonescimab plus pemetrexed disodium was administered, but disease progression persisted...Our case demonstrates that the lung cancer organoids serve as a powerful preclinical platform for individualized treatment selection in patients with advanced lung adenocarcinoma via rapid functional drug screening. This personalized strategy shows great potential to optimize clinical outcomes for heavily pretreated patients.

SG's success in breast cancer and broad expression in epithelial tumors has sparked interest in its potential applicability to CRC. This review provides an overview of SG's mechanism of action and current clinical applications, discussing its therapeutic potential in the context of CRC.