Datopotamab Deruxtecan BLA Submitted to FDA for EGFR-Mutated NSCLC
核心洞察
AstraZeneca and Daiichi Sankyo submitted a BLA to the FDA for datopotamab deruxtecan (Dato-DXd) to treat adults with metastatic or locally advanced EGFR-mutated NSCLC (搜索) who have received prior treatment.
The BLA submission is based on data from the phase 2 TROPION-Lung05 study and pooled analysis from TROPION-Lung01, demonstrating enhanced efficacy in EGFR (搜索)-mutant NSCLC (搜索).
In the TROPION-Lung05 trial, Dato-DXd showed a confirmed objective response rate of 43.6% in patients with EGFR (搜索) mutations, with a median duration of response of 7.0 months.
The FDA has received a biologics license application (BLA) for datopotamab deruxtecan (Dato-DXd) as a potential treatment for adult patients with metastatic or locally advanced non-small cell lung cancer (NSCLC (搜索)) harboring EGFR (搜索) mutations, specifically those who have previously undergone treatment. This submission, a collaborative effort between AstraZeneca and Daiichi Sankyo, follows feedback from the FDA and replaces a prior BLA for nonsquamous NSCLC. The new application is supported by data from the phase 2 TROPION-Lung05 study and data from the phase 3 TROPION-PanTumor01 and TROPION-Lung01 trials.
Clinical Efficacy in EGFR-Mutated NSCLC
The decision to focus the BLA on EGFR-mutated NSCLC (搜索) was informed by the pronounced benefit observed in this patient population within the TROPION-Lung05 and TROPION-Lung01 trials. Susan Galbraith, Executive Vice President of Oncology Research and Development at AstraZeneca, noted that TROPION-Lung01 demonstrated the potential to improve upon standard-of-care chemotherapy in a broad, previously treated, advanced lung cancer population, with particularly encouraging results in patients with EGFR (搜索) mutations. Data from the TROPION-Lung05 trial, presented at the 2023 ESMO Congress, showed a confirmed objective response rate (cORR) of 43.6% in patients with EGFR mutations (n = 78). The median duration of response (DOR) was 7.0 months (95% CI, 4.2-10.2), the confirmed disease control rate (DCR) was 82.1% (95% CI, 71.7%-89.8%), and the median progression-free survival (PFS) was 5.8 months (95% CI, 5.4-8.3).
TROPION-Lung05 Trial Details
The phase 2 TROPION-Lung05 study enrolled patients with stage IIIB, IIIC, or IV NSCLC (搜索) with an ECOG performance status of 0 or 1 and at least one actionable genomic alteration, including EGFR (搜索), ALK, ROS1, NTRK, BRAF, MET exon 14 skipping, or RET. Participants had received at least one line of targeted therapy and one or two cytotoxic agent-containing regimens, including platinum-based therapy in the metastatic setting, and had experienced radiographic disease progression following targeted treatment. In the overall study population (n = 137), Dato-DXd achieved a cORR of 35.8% (95% CI, 27.8%-44.4%), with 3% of patients achieving a complete response and 33% experiencing a partial response. The median DOR in all treated patients was 7.0 months (95% CI, 4.2-9.8), the confirmed DCR was 78.8% (95% CI, 71.0%-85.3%), and the median PFS was 5.4 months (95% CI, 4.7-7.0).
Safety Profile
The safety profile of Dato-DXd was also evaluated in the TROPION-Lung05 trial. Grade 3 or higher treatment-emergent adverse events (TEAEs) were observed in 47.4% of all patients, with serious TEAEs occurring in 24.8%. Dose reductions were required in 21.9% of patients, and drug discontinuations due to TEAEs occurred in 9.5%. TEAEs led to death in 1.5% of patients.
About Datopotamab Deruxtecan
Datopotamab deruxtecan is an antibody-drug conjugate (ADC) composed of a human anti-TROP2 (搜索) IgG1 monoclonal antibody covalently linked to a potent topoisomerase I inhibitor payload via a plasma-stable, tumor-selective, tetrapeptide-based cleavable linker. It is currently under evaluation in over 20 clinical trials across multiple cancers, including NSCLC (搜索), triple-negative breast cancer, and hormone receptor-positive, HER2-low or -negative breast cancer. Phase 3 trials are ongoing to assess Dato-DXd as a monotherapy and in combination with other anticancer treatments in lung and breast cancer.