Datopotamab Deruxtecan Demonstrates Significant Survival Benefit Over Chemotherapy in Advanced Nonsquamous NSCLC: TROPION-Lung01 Phase III Trial Results

Monday, May 27, 2024

The high-level overall survival (OS) results from the TROPION-Lung01 Phase III trial showed that datopotamab deruxtecan (Dato-DXd) had a numerical advantage over docetaxel in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) who had undergone at least one prior line of therapy.

However, the OS results did not achieve statistical significance in the overall trial population. In a predefined subgroup of patients with nonsquamous NSCLC, datopotamab deruxtecan demonstrated a clinically meaningful improvement in OS compared to docetaxel, which is the current standard-of-care chemotherapy.

These final OS findings build on the positive progression-free survival (PFS) results presented at the 2023 European Society for Medical Oncology Congress. At that time, datopotamab deruxtecan showed a statistically significant improvement in PFS across the overall trial population and a clinically meaningful benefit in patients with nonsquamous NSCLC.

In the TROPION-Lung01 trial, patient enrollment by tumor histology was balanced across treatment arms and aligned with real-world incidence, with approximately 75% of patients having nonsquamous NSCLC.

The safety profile of datopotamab deruxtecan in the TROPION-Lung01 trial was consistent with previous analyses, with fewer dose reductions or discontinuations due to adverse events compared to docetaxel, and no new safety concerns were identified. Additionally, no new cases of interstitial lung disease of any grade were determined to be drug-related.

Executive Vice President of Oncology R&D at AstraZeneca, stated: “Datopotamab deruxtecan is the only investigational therapy to show a clinically meaningful survival improvement in patients with previously treated nonsquamous non-small cell lung cancer compared to docetaxel, which has long been unsurpassed in this post-targeted treatment and post-immunotherapy setting.

These results reinforce the potential for datopotamab deruxtecan to replace conventional chemotherapy in this late-line setting and bolster our confidence in ongoing trials evaluating this therapy in first-line lung cancer.”

The improvement in overall survival seen with datopotamab deruxtecan, along with the previously reported clinically meaningful progression-free survival, more than doubling of overall response, and prolonged duration of response compared to docetaxel.

suggest that this TROP2-directed antibody-drug conjugate could potentially become an important new treatment for patients with nonsquamous non-small cell lung cancer in this advanced setting.

These data will support our ongoing discussions with regulatory authorities globally to potentially bring datopotamab deruxtecan to patients as quickly as possible and mark another step forward in creating new standards of care for patients with cancer.”

The data will be presented at an upcoming medical meeting and will support regulatory applications currently under review globally, including in the US and EU, for the treatment of adult patients with locally advanced or metastatic nonsquamous NSCLC who have received prior systemic therapy.


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