SAPPORO MEDICAL UNIVERSITY

Datopotamab deruxtecan, an investigational TROP2-directed ADC, is being evaluated in multiple clinical trials for advanced NSCLC, including TROPION-Lung05, TROPION-Lung01, and TROPION-PanTumor01. These trials assess efficacy and safety in patients with actionable genomic alterations and those requiring systemic therapy following prior treatment. Primary endpoints include objective response rate (ORR) and progression-free survival (PFS). AstraZeneca and Daiichi Sankyo collaborate on the development and commercialization of datopotamab deruxtecan.

TROPION-Breast01 Phase III trial of datopotamab deruxtecan did not achieve statistical significance in overall survival (OS) analysis for inoperable or metastatic HR-positive, HER2-low or negative breast cancer patients, despite meeting progression-free survival (PFS) primary endpoint. Safety profile consistent with previous analysis, with no new safety concerns. Multiple ADCs approved during trial likely affected survival results. AstraZeneca and Daiichi Sankyo continue discussions with regulatory authorities and clinical development for datopotamab deruxtecan.

Final overall survival results from TROPION-Breast01 Phase III trial of datopotamab deruxtecan (Dato-DXd) did not achieve statistical significance in HR-positive, HER2-low or negative breast cancer patients, despite positive progression-free survival results. Safety profile remained consistent with no new concerns. Subsequent treatment options likely affected survival results.

TROPION-Lung01 trial results show datopotamab deruxtecan (12.9 months OS) vs. docetaxel (11.8 months OS) in overall population, with nonsquamous histology showing 14.6 months vs. 12.3 months OS. In patients with actionable genomic alterations, datopotamab deruxtecan showed 15.6 months OS compared to 9.8 months with docetaxel. NeoCOAST-2 trial preliminary results indicate 34.1% pCR and 65.9% mPR with datopotamab deruxtecan plus Imfinzi and carboplatin in early-stage NSCLC.

IMFINZI is indicated for various lung cancer treatments, including unresectable Stage III NSCLC, metastatic NSCLC, extensive-stage SCLC, and biliary tract cancer. It also treats unresectable HCC in combination with IMJUDO. TROPION-Lung01 and NeoCOAST-2 are Phase III and II trials evaluating datopotamab deruxtecan and IMFINZI, respectively, in lung cancer. AstraZeneca collaborates with Daiichi Sankyo for ADC development and aims to improve lung cancer outcomes.