Datopotamab Deruxtecan Met Dual Primary Endpoint of Progression-Free Survival in Patients With Advanced Non-Small Cell Lung Cancer in TROPION-Lung01 Phase III Trial

Positive high-level results from the TROPION-Lung01 Phase III trial showed datopotamab deruxtecan (Dato-DXd) demonstrated a statistically significant improvement for the dual primary endpoint of progression-free survival (PFS) compared to docetaxel, the current standard of care chemotherapy, in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) treated with at least one prior therapy.

For the dual primary endpoint of overall survival (OS), the data were not mature and an early trend was observed in favor of datopotamab deruxtecan versus docetaxel that did not meet the prespecified threshold for statistical significance at this interim analysis. The trial will continue as planned to assess OS with greater maturity. The investigators and participants will remain blinded to the results.

The safety profile of datopotamab deruxtecan was consistent with previous clinical trials with no new safety signals identified. All grade interstitial lung disease was generally consistent with prior clinical trials, with the majority being low grade. Some Grade 5 events were observed.

Datopotamab deruxtecan is a specifically engineered TROP2-directed DXd antibody drug conjugate (ADC) being jointly developed by AstraZeneca and Daiichi Sankyo.

Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: “With TROPION-Lung01, we met the dual primary endpoint of progression-free survival, challenging the entrenched standard of care in a previously treated and unselected patient population that has long deserved an alternative to chemotherapy. These first Phase III trial results from the datopotamab deruxtecan clinical program provide compelling evidence for the potential role this TROP2-directed antibody drug conjugate can play in treating patients with lung cancer.”

Ken Takeshita, MD, Global Head, Oncology R&D, Daiichi Sankyo, said: “We are encouraged by the statistically significant results of the dual primary endpoint of progression-free survival seen with datopotamab deruxtecan and look forward to the final overall survival analysis. We plan to share these data with regulatory authorities to discuss next steps.”

More than one million people worldwide are diagnosed with advanced NSCLC each year.^1,2 While immunotherapy and targeted therapies have improved outcomes in the 1st-line metastatic setting, most patients eventually experience disease progression and receive chemotherapy.^3-5 For decades, chemotherapy has been the last treatment available for patients with advanced NSCLC in the absence of other treatment options and despite limited effectiveness and known side effects.^3-5 TROP2 is a protein highly expressed in a large majority of lung cancers. There are currently no TROP2-directed ADCs approved for the treatment of patients with lung cancer.^6-8