Datopotamab deruxtecan (Dato-DXd) is an investigational TROP2 directed ADC that is designed using Daiichi Sankyo’s proprietary DXd ADC technology. Datopotamab deruxtecan is one of the three lead ADCs in the oncology pipeline of Daiichi Sankyo, and one of the most advanced programs in AstraZeneca’s ADC scientific platform. According to the data presented at the ASCO 2023, at the data cutoff on April 7, 2023, around 58% and 75% of patients were receiving doublet or triplet therapy, and they were treated in the 1L setting. The detailed results for the TROPION-Lung02 study are explained below in the table.
Summary of Efficacy Results
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In terms of safety data, datopotamab deruxtecan-based combinations maintain safety profiles in line with previous data, unveiling no new safety signals. Grade 3 or higher Treatment-Related adverse events (TRAEs) were encountered in 31% of patients on doublet therapy and 58% on triplet therapy. Across treatment cohorts, there were 27 interstitial lung disease (ILD) or pneumonitis events adjudicated as drug-related by an independent committee.
KOL insights
“Nearly all patients with advanced non-small cell lung cancer experience disease progression following initial therapy, underscoring the need for novel therapeutic approaches across treatment lines.” –Expert Opinion.
“These early data give us confidence in the ongoing phase 3 development program evaluating datopotamab deruxtecan combinations as potential first-line treatment options for patients with advanced lung cancer across tumor histologies and PD-L1 expression levels.” –Expert Opinion.
Conclusion
More than one million people are diagnosed with advanced stage NSCLC each year. Initial therapy utilizing immune checkpoint inhibitors, with or without chemotherapy, enhances results for NSCLC patients lacking actionable genomic alterations such as EGFR or ALK. Nevertheless, disease progression remains a challenge for the majority of patients over time. Importantly, TROP2 is a protein expressed in more than 90% of NSCLC tumors, and currently there are no TROP2 directed ADCs approved for the treatment of lung cancer.
TROPION-Lung02 is the first study evaluating datopotamab deruxtecan + pembrolizumab ± platinum chemotherapy in advanced NSCLC without actionable genomic alterations. Based on the above findings, the combination demonstrated encouraging antitumor activity in patients with first line and second line and above settings. Apart from that, datopotamab deruxtecan + pembrolizumab ± platinum chemotherapy is also being compared with standard of care therapies in the 1L setting in the pivotal Phase III TROPION-Lung07 and TROPION-Lung08 trials. Lastly, these updated TROPION-Lung02 findings indicate the potential of datopotamab deruxtecan combinations in enhancing outcomes for NSCLC patients, marking a significant milestone in the quest for a novel standard treatment beyond immunotherapy. These results propel hope for improved therapeutic approaches for NSCLC
