Datopotamab Deruxtecan Improves Survival Over Chemotherapy in Advanced Nonsquamous NSCLC (TROPION-Lung01)

Datopotamab deruxtecan, a TROP2 directed DXd antibody-drug conjugate developed by Daiichi Sankyo and AstraZeneca, has shown promising results in the TROPION-Lung01 phase 3 trial. This trial focused on adult patients with advanced or metastatic non-small cell lung cancer (NSCLC) who had already received at least one prior line of therapy. While the overall survival (OS) results numerically favored datopotamab deruxtecan over docetaxel, they did not achieve statistical significance across the entire trial population. However, in a pre-specified subgroup of patients with nonsquamous NSCLC, the drug significantly improved OS compared to docetaxel, which remains the current standard of care.

The TROPION-Lung01 study had previously met its dual primary endpoint of progression-free survival (PFS), with the final OS analysis reinforcing these positive outcomes. At the European Society for Medical Oncology 2023 Congress, data showed that datopotamab deruxtecan significantly improved PFS for the overall trial population and provided a meaningful PFS benefit for patients with nonsquamous NSCLC. Approximately 75% of patients enrolled in TROPION-Lung01 had nonsquamous NSCLC, reflecting the real-world incidence of this cancer type.

Safety data for datopotamab deruxtecan in this trial were consistent with previous analyses. The drug was associated with fewer dose reductions or discontinuations due to adverse events compared to docetaxel, and no new significant safety concerns were identified, including the absence of new interstitial lung disease events.

The enhanced survival and response metrics observed with datopotamab deruxtecan are promising. Dr. Ken Takeshita, Global Head of R&D at Daiichi Sankyo, suggested that these results highlight the potential of this drug to become a valuable treatment for patients with advanced nonsquamous NSCLC. The company plans to discuss these findings with global regulatory authorities to expedite the availability of datopotamab deruxtecan as a new standard of care.

Dr. Susan Galbraith, Executive Vice President of Oncology R&D at AstraZeneca, emphasized the uniqueness of datopotamab deruxtecan in providing a meaningful survival advantage over existing chemotherapy options like docetaxel. These findings support ongoing trials of the drug in first-line lung cancer treatment settings.

TROPION-Lung01 is a comprehensive phase 3 trial that enrolled approximately 600 patients across various regions, including Asia, Europe, North America, Oceania, and South America. The study's dual primary endpoints were PFS and OS, with several key secondary endpoints such as objective response rate, duration of response, and safety.

Lung cancer remains a significant global health challenge, with nearly 2.5 million cases diagnosed worldwide in 2022. NSCLC accounts for about 80% of these cases, with 75% and 25% of tumors being of nonsquamous and squamous histology, respectively. Despite advancements in immunotherapy and targeted treatments, many patients eventually require chemotherapy due to disease progression. Current chemotherapy options like docetaxel are limited by their efficacy and side effects, which underscores the need for new treatments like datopotamab deruxtecan.

Datopotamab deruxtecan is part of a broader collaboration between Daiichi Sankyo and AstraZeneca, which includes developing multiple antibody-drug conjugates (ADCs) targeting various cancers. This partnership aims to leverage Daiichi Sankyo’s proprietary DXd ADC technology, which combines monoclonal antibodies with topoisomerase I inhibitor payloads, to deliver targeted cancer therapies.

Overall, the findings from the TROPION-Lung01 trial represent a significant step forward in the treatment of advanced nonsquamous NSCLC, offering hope for improved outcomes for patients who have exhausted other therapeutic options. The data will be presented at an upcoming medical meeting and contribute to ongoing regulatory review processes in the U.S. and EU.