Trodelvy (sacituzumab govitecan-hziy)

P=N/A, N=200, Recruiting, Zhejiang Cancer Hospital | Not yet recruiting --> Recruiting

P3, N=640, Active, not recruiting, Gilead Sciences | Recruiting --> Active, not recruiting

In Caucasian AEG/S patients, TROP2 is expressed in the majority of cases. TROP2 expression intensity itself has an impact on survival, which could be explained by a more aggressive phenotype, which leads to lymphatic invasion and lymph node metastasis.

P2, N=30, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Dec 2026 --> Jul 2028 | Trial primary completion date: Dec 2025 --> Jul 2028

P1/2, N=120, Not yet recruiting, National Cancer Institute (NCI)

P1/2, N=58, Completed, Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest | Active, not recruiting --> Completed | Trial completion date: Mar 2027 --> Jan 2026 | Trial primary completion date: Feb 2027 --> Jan 2026

In HR+ early BC, the SOFT/TEXT 15-year update confirmed the benefit of ovarian suppression plus endocrine therapy, while OASIS-4 showed elinzanetant reduced endocrine-related vasomotor symptoms. In early TNBC, NRG-BR003 found no survival benefit from adding carboplatin...In advanced disease, DESTINY-Breast09 established trastuzumab deruxtecan plus pertuzumab as superior first-line therapy. SERENA-6 and VERITAC-2 highlighted ESR1-targeted strategies, while ASCENT-04/KEYNOTE-D19 demonstrated sacituzumab govitecan plus pembrolizumab improved outcomes in PD-L1-positive advanced TNBC.

Pre-therapeutic UGT1A1 genotyping is increasingly performed in patients receiving irinotecan, as its active metabolite SN-38 is primarily cleared through UGT1A1-mediated glucuronidation. Furthermore, a statistically significant increased risk was found for developing grade ≥ 3 diarrhea or febrile neutropenia in this group. Although the meta-analysis was underpowered due to small sample sizes, the pharmacological analysis demonstrated higher SN-38 levels in patients treated with sacituzumab govitecan, supporting the rationale for UGT1A1 genotyping in this context.

Furthermore, two prodrug derivatives of compound 20 were designed to improve aqueous solubility, achieving dose-proportional systemic exposure in rats during dose-escalation preclinical toxicity studies. Additionally, the combination of prodrug 22 with TrodelvyⓇ, a TROP2 ADC, demonstrated synergistic antitumor activity in triple-negative breast cancer MDA-MB-231 xenograft models.

Clinical studies of antibody-drug conjugates such as trastuzumab emtansine (T-DM1), trastuzumab deruxtecan (T-DXd), and sacituzumab govitecan have demonstrated significant improvements in progression-free survival and overall survival across diverse breast cancer patient populations. It covers mechanistic insights, linker-payload innovations, receptor-based targeting approaches, clinical trial progress, and next-generation modalities that extend beyond HER2-directed ADCs. Current challenges, safety profiles, and future opportunities in engineering more selective and effective ADC platforms are also discussed.

TROPION-Breast01 met its dual primary endpoint of PFS by BICR. While there was no statistically significant improvement in the dual primary endpoint of OS with Dato-DXd versus ICC, subsequent ADC treatment may have affected OS results. The totality of efficacy and safety data support Dato-DXd as a new treatment option for patients with previously treated, inoperable/metastatic HR+/HER2‒ breast cancer.