Trodelvy (sacituzumab govitecan-hziy)

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.

P3, N=376, Recruiting, MediLink Therapeutics (Suzhou) Co., Ltd. | Not yet recruiting --> Recruiting

On the therapeutic front, &lsqb;177Lu]Lu-T142 elicited marked tumor regression in Trop2-positive models, while its combination with Trodelvy produced synergistic antitumor effects without significant systemic toxicity. Collectively, these results highlighted &lsqb;68Ga]Ga-T142 and &lsqb;177Lu]Lu-T142 as a highly promising Trop2-targeted theranostic platform, with strong potential for precise diagnosis, therapy monitoring, and personalized treatment of Trop2-expressing pancreatic cancer.

Patients will be stratified based on programmed death receptor-ligand 1 (PD-L1) tumor expression and randomized (1:1:1) to observation for 10 months (Arm 1), zimberelimab for 13 cycles (Arm 2) or sacituzumab govitecan and zimberelimab for 8 cycles followed by zimberelimab monotherapy for 5 cycles (Arm 3). The primary endpoint is disease-free survival, and secondary endpoints include overall survival and safety.

Trastuzumab deruxtecan expanded therapeutic utility across HER2-low and HER2-ultralow disease, whereas sacituzumab govitecan and datopotamab deruxtecan provide later-line options. Ultimately, management of hormone receptor-positive/HER2-negative MBC requires dynamic integration of tumor biology, systemic therapy advances, and patient-defined goals of care. As therapeutic complexity increases, shared decision making and equitable access to evidence-based and supportive care services remain essential for delivering high-quality, individualized oncology care.

SG demonstrated encouraging efficacy in a pretreated population that included biologically aggressive recurrent EC. Adverse events were consistent with the known safety profile.