▎WuXiEdited by Kant Content Team

AstraZeneca and Daiichi Sankyo announced today that, based on feedback from the U.S. FDA, the two companies have submitted a Biologics License Application (BLA) for their jointly developed Trop2-targeted antibody-drug conjugate (ADC), datopotamab deruxtecan (Dato-DXd), seeking accelerated approval for the therapy to treat patients with epidermal growth factor receptor (EGFR) locally advanced or metastatic non-small cell lung cancer (NSCLC) in adult patients with mutations, who have previously received systemic treatment (including EGFR-targeted therapy). At the same time, the two companies voluntarily withdrew the previous BLA submitted to the FDA for the treatment of advanced or metastatic non-squamous NSCLC patients.

This new BLA submission is primarily based on the positive results from the Phase 2 TROPION-Lung05 clinical trial, supported by data from the Phase 3 TROPION-Lung01 and Phase 1 TROPION-PanTumor01 clinical trials.TROPION-Lung05 and TROPION-Lung01 trials evaluate datopotamab deruxtecan in previously treatedEGFREfficacy and Safety in Patients with Mutant NSCLC: Pooled Analysis Results from Two Trials to Be Presented at the Upcoming‍Presented at the ESMO Asia 2024 Congress.

The results of the previously announced TROPION-Lung01 Phase 3 clinical trial showed that, compared with the current standard of care, docetaxel,Patients with locally advanced or metastatic NSCLC treated with datopotamab deruxtecan showed a statistically significant improvement in progression-free survival (PFS), one of the dual primary endpoints.These patients had previously received at least one prior therapy. The safety of datopotamab deruxtecan was consistent with the results observed in other ongoing trials, with no new safety issues identified.

And this yearAmerican Society of Clinical Oncology (ASCO) Annual MeetingThe partial results of the TROPION-Lung05 trial, as announced,18 patients with target brain lesionsThe intracranial (IC) objective response rate (ORR) was 22% (95% CI: 6–48), and the IC disease control rate (DCR) was 72% (95% CI: 47–90) in previously treated patients with locally advanced or metastatic NSCLC.。Of the 18 patients, 10 (56%) experienced a reduction in the total diameter of brain tumors.

Datopotamab deruxtecan is a Trop2-targeted ADC. Designed using Daiichi Sankyo's proprietary DXd ADC technology.Datopotamab deruxtecan is generated by conjugating a humanized anti-Trop2 monoclonal antibody with multiple topoisomerase I inhibitor payloads (DXd) through a cleavable tetrapeptide linker.

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References:

[1] Datopotamab deruxtecan new BLA submitted for accelerated approval in the US for patients with previously treated advanced EGFR-mutated non-small cell lung cancer. Retrieved November 12, 2024 from https://www.astrazeneca.com/media-centre/press-releases/2024/dato-dxd-new-bla-submitted-nsq-bla-withdrawn.html

[2] Intracranial efficacy of datopotamab deruxtecan (Dato-DXd) in patients (pts) with previously treated advanced/metastatic non-small cell lung cancer (a/m NSCLC) with actionable genomic alterations (AGA): Results from TROPION-Lung05. Retrieved November 12, 2024 from https://ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.8593

[3] Datopotamab deruxtecan Biologics License Application accepted in the US for patients with previously treated advanced nonsquamous non-small cell lung cancer. Retrieved February 19, 2024 from https://www.astrazeneca.com/media-centre/press-releases/2024/fda-accepts-dato-dxd-bla-for-nonsquamous-nsclc.html

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