Jiataile (sacituzumab tirumotecan)

While TROP2-targeted antibody-drug conjugates (ADCs), such as sacituzumab govitecan, sacituzumab tirumotecan, and datopotamab deruxtecan (DXD), achieved clinical success, the mechanisms underlying resistance to these therapies remain incompletely understood. R7059-DXD is a differentiated, epitope-distinct TROP2-targeted ADC with the potential to overcome resistance to existing therapies. These findings support its further clinical development as a novel treatment for TROP2-expressing malignancies, including in patients previously treated with sacituzumab- or datopotamab-based regimens.

P2, N=43, Recruiting, Second Affiliated Hospital, School of Medicine, Zhejiang University

Importantly, early clinical studies demonstrated that the EGFR-targeted ADC MRG003 and the TROP2-targeted ADC Sac-TMT showed notable efficacy in patients with refractory ACC and high expression of these targets. This pioneering study introduces a biomarker-based stratification system, categorizing ACC patients by histological subtype and target expression profiles, EGFR/TROP2 for non-solid ACC and B7-H4/Nectin-4 for solid ACC, to inform ADC therapy decisions.

P2, N=75, Not yet recruiting, Fudan University

This study estimated the cost-effectiveness of sacituzumab tirumotecan (Sac-TMT) versus pemetrexed-platinum chemotherapy as second-line therapy for advanced EGFR-mutated non-small cell lung cancer (NSCLC) in China. A price reduction exceeding 73.81% would bring the ICER below the WTP threshold. At current prices, Sac-TMT is not cost-effective as second-line therapy for advanced EGFR-mutated NSCLC in China.

An ongoing phase 2 trial evaluating first-line sac-TMT plus osimertinib combination therapy in patients with advanced EGFR-mutant NSCLC shows preliminary efficacy. Together, our findings establish TROP2 as a therapeutically actionable vulnerability in DTP cells and support the clinical development of TROP2-ADC combined with EGFR-TKI as a first-line strategy to delay TKI resistance and improve outcomes in EGFR-mutant NSCLC.

P1/2, N=190, Recruiting, Merck Sharp & Dohme LLC | Trial completion date: May 2037 --> Apr 2032

P2, N=20, Not yet recruiting, Virginia Commonwealth University

P3, N=420, Not yet recruiting, Fudan University

P2, N=24, Recruiting, Fudan University

P2, N=20, Active, not recruiting, Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd. | Recruiting --> Active, not recruiting

Among patients with PD-L1-positive advanced NSCLC without targetable genomic alterations, first-line treatment with sac-TMT plus pembrolizumab significantly prolonged progression-free survival compared with pembrolizumab alone. Therefore, sac-TMT plus pembrolizumab has the potential to redefine first-line treatment for patients with PD-L1-positive advanced NSCLC without targetable genomic alterations.