Datopotamab Deruxtecan Demonstrates Meaningful Survival Improvement in Advanced Non-Small Cell Lung Cancer in TROPION-Lung01 Phase III Study

The TROPION-Lung01 Phase III trial indicated that patients with advanced nonsquamous non-small cell lung cancer (NSCLC) treated with datopotamab deruxtecan experienced a clinically significant improvement in overall survival (OS) compared to those receiving chemotherapy. Despite numerical favorability towards datopotamab deruxtecan, the overall survival results did not reach statistical significance in the entire trial population.

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Previously, TROPION-Lung01 achieved one of its primary goals, showing progression-free survival (PFS) benefits. These findings are instrumental for ongoing regulatory reviews in regions including the US and EU.

The trial's high-level OS results, which had already demonstrated PFS advantages, showed that datopotamab deruxtecan (Dato-DXd) outperformed docetaxel in patients with locally advanced or metastatic NSCLC who had undergone at least one prior therapy. While the overall OS improvement was not statistically significant, the subgroup with nonsquamous NSCLC showed notable clinical benefits over the standard chemotherapy, docetaxel.

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The detailed OS analysis complements earlier PFS data presented at the 2023 European Society for Medical Oncology Congress, which highlighted significant PFS improvements for datopotamab deruxtecan across the trial population and particularly in nonsquamous NSCLC patients. Approximately 75% of participants had nonsquamous NSCLC, reflecting real-world distributions.

Datopotamab deruxtecan's safety profile remained consistent with prior analyses, showing fewer dose reductions or therapy discontinuations due to side effects compared to docetaxel. Importantly, no new safety issues, including drug-related interstitial lung disease, were identified.

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Jointly developed by AstraZeneca and Daiichi Sankyo, datopotamab deruxtecan is a TROP2-directed DXd antibody drug conjugate. The latest trial data will be presented at an upcoming medical conference and support ongoing regulatory applications in various global regions for treating adults with locally advanced or metastatic nonsquamous NSCLC who have undergone previous systemic therapy.

TROPION-Lung01 is a global, randomized, multicenter, open-label Phase III study assessing the efficacy and safety of datopotamab deruxtecan (6.0mg/kg) versus docetaxel (75mg/m2) in adults with advanced or metastatic NSCLC with and without actionable genomic alterations who need systemic therapy after previous treatment. Those with actionable genomic alterations had prior platinum-based chemotherapy and targeted therapy, while those without had prior platinum-based chemotherapy and PD-1 or PD-L1 inhibitors.

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The study's primary endpoints are PFS, as evaluated by blinded independent central review (BICR), and OS. Key secondary endpoints include PFS assessed by investigators, objective response rate, duration and time to response, disease control rate (evaluated by both BICR and investigators), and safety.

In 2022, nearly 2.5 million new lung cancer cases were reported globally. NSCLC accounts for approximately 80% of these cases, with about 75% being nonsquamous and 25% squamous. Despite advances in first-line treatments with immunotherapy and targeted therapies, most patients eventually face disease progression and resort to chemotherapy, which has long been the final treatment option despite its limited efficacy and well-known side effects.

TROP2 is widely present in most NSCLC tumors. Currently, there is no approved TROP2-directed antibody-drug conjugate (ADC) for lung cancer treatment.