AstraZeneca and Daiichi Sankyo's TROP2 ADC Dato-DXd Meets Primary PFS Endpoint in First Phase III Trial for Previously Treated NSCLC

On July 3, AstraZeneca and Daiichi Sankyo jointly announced that the Phase III TROPION-lung 01 study of Dato-DXd (datopotamab deruxtecan, DS-1062) for patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) who have previously received at least one treatment met the primary endpoint of progression-free survival (PFS). Data on the other primary endpoint, overall survival (OS), are not yet mature. According to the press release, this is the first Phase III clinical result for Dato-DXd.

TROPION-Lung01 is a randomized, open-label global multicenter Phase III clinical trial designed to evaluate the efficacy and safety of Dato-DXd (6.0mg/kg) versus docetaxel (75mg/m²) in patients with locally advanced or metastatic NSCLC who have previously received at least one prior treatment. The primary endpoints of the study are overall survival (OS) and progression-free survival (PFS) assessed by a blinded independent central review committee (BICR). Key secondary endpoints include investigator-assessed PFS, objective response rate (ORR), duration of response, time to response, as well as disease control rates evaluated by BICR and investigators, and safety.

The results showed that the study met the primary endpoint of PFS with a statistically significant improvement. The primary endpoint of OS has not yet matured, but a trend favoring Dato-DXd was observed in the interim analysis. In terms of safety, the data were consistent with previous findings, with no new safety signals observed. Interstitial lung disease (ILD) events were mostly low-grade.

Dato-DXd is a TROP2 ADC developed through the collaboration between AstraZeneca and Daiichi Sankyo, designed using Daiichi Sankyo's proprietary DXd ADC technology. It consists of a humanized anti-TROP2 IgG1 monoclonal antibody, co-developed with Sapporo Medical University, linked via a cleavable tetrapeptide linker to multiple topoisomerase I inhibitor payloads (a derivative of exatecan).

Source: AstraZeneca Official Website

Currently, Dato-DXd is undergoing the global TROPION series of clinical development programs, aiming to evaluate its efficacy and safety across various solid tumors, including NSCLC, triple-negative breast cancer, HR-positive/HER2-low or negative breast cancer. Additionally, the product is being assessed in multiple clinical trials using new combination approaches.

Source: Daiichi Sankyo Official Website

据统计，每年有超过一百万人被诊断为晚期NSCLC。虽然一线免疫检查点抑制剂±化疗治疗方案改善了无靶向基因组改变（如EGFR或ALK）的NSCLC患者的预后，但大多数患者仍会出现疾病进展。TROP2是一种表达于90%以上的非小细胞肺癌的蛋白质，目前没有靶向TROP2的ADC药物被批准用于肺癌治疗。

Currently, globally, only Gilead's Trodelvy (sacituzumab govitecan), a TROP2 ADC, has been approved for marketing, with indications including urothelial carcinoma, HR-positive breast cancer, and triple-negative breast cancer.

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