Positive high-rate results from AstraZeneca’s TROPION-Lung01 phase III trial showed datopotamab deruxtecan (Dato-DXd) showed a statistically significant improvement for the dual primary end point of progression-free survival (PFS) compared to docetaxel, the current standard of chemotherapy treatment, in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) treated with at least one prior therapy.
For the overall survival (OS) dual primary endpoint, the data were immature and an early trend was observed in favor of datopotamab deruxtecan versus docetaxel which did not meet predetermined thresholds for statistical significance in this interim analysis. The trials will continue as planned to assess the OS with greater maturity. Investigators and participants will remain in the dark about the results.
The safety profile of datopotamab deruxtecan is consistent with previous clinical trials with no new safety signals identified. All grades of interstitial lung disease were generally consistent with previous clinical trials, with the majority being low grade. Several Class 5 events were observed.
Datopotamab deruxtecan is a specially engineered DXd antibody drug (ADC) conjugate co-developed by AstraZeneca and Daiichi Sankyo.
“Convincing evidence” according to AstraZeneca
Susan Galbraith, executive vice president, R&D oncology, AstraZeneca, said: “With TROPION-Lung01, we are meeting the dual primary endpoint of progression-free survival, challenging entrenched standards of care in long-viable previously treated and non-selected patient populations. Get alternative chemotherapy. The results of the first phase III trial of the datopotamab deruxtecan clinical program provide strong evidence for the potential role that this TROP2-directed antibody drug conjugate could play in treating patients with lung cancer.
Ken Takeshita, global head, oncology R&D, Daiichi Sankyo, said: “We are encouraged by the statistically significant results from the dual primary end point of progression-free survival seen with datopotamab deruxtecan and look forward to the final analysis of overall survival. We plan to share this data with the authorities to discuss next steps.”
More than one million people worldwide are diagnosed with advanced NSCLC each year. While immunotherapy and targeted therapy have improved outcomes in the first-line metastatic setting, the majority of patients eventually progress to disease progression and receive chemotherapy.
For decades, chemotherapy has been the last available treatment for patients with advanced NSCLC in the absence of other treatment options and despite limited effectiveness and known side effects. TROP2 is a protein that is highly expressed in most lung cancers. There are currently no TROP2-directed ADCs approved for the treatment of patients with lung cancer.
TROPION-Lung01 enrolls patients with and without actionable genomic changes, such as EGFR and ALK. Patients with actionable genomic alterations were previously treated with platinum-based chemotherapy and approved targeted therapy. Patients without previous actionable genomic alterations were treated, concomitantly or sequentially, with platinum-based chemotherapy and PD-1 or PD-L1 inhibitors.