FDA Considers Dato-DXd for Accelerated Approval in Pretreated EGFR-Mutated NSCLC
Key Insights
The FDA is reviewing a BLA for datopotamab deruxtecan (Dato-DXd) for EGFR (search)-mutated NSCLC (search) after prior systemic therapies, including EGFR-directed treatments.
The application is supported by phase 2 TROPION-Lung05 data, showing a 43.6% ORR and 5.8-month median PFS in previously treated patients.
AstraZeneca and Daiichi Sankyo voluntarily withdrew the BLA for Dato-DXd in advanced or metastatic nonsquamous NSCLC (search) after TROPION-Lung01 results.
The FDA is evaluating a biologics license application (BLA) seeking accelerated approval for datopotamab deruxtecan (Dato-DXd) for treating adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC (search)) harboring EGFR mutations (search), who have previously undergone systemic therapies, including EGFR (search)-directed treatments. AstraZeneca and Daiichi Sankyo voluntarily withdrew a prior BLA for Dato-DXd in advanced or metastatic nonsquamous NSCLC.
The new BLA is supported by data from the phase 2 TROPION-Lung05 trial, along with data from TROPION-Lung01 and the phase 1 TROPION-PanTumor01 trial.
TROPION-Lung05 Trial Results
Findings from TROPION-Lung05, presented at the 2023 ESMO Congress, indicated that patients with previously treated, EGFR (search)-mutated advanced NSCLC (search) (n = 74) achieved an overall response rate (ORR) of 43.6% (95% CI, 32.4%-55.3%) and a disease control rate (DCR) of 82.1% (95% CI, 71.7%-89.8%). The median duration of response was 7.0 months (95% CI, 4.2-10.2), and the median progression-free survival (PFS) was 5.8 months (95% CI, 5.4-8.3).
Breakthrough Therapy Designation
The FDA previously granted breakthrough therapy designation to Dato-DXd for EGFR (search)-mutated NSCLC (search) progressing after EGFR TKI and platinum-based chemotherapy. A pooled analysis of TROPION-Lung05 (n = 78) and TROPION-Lung01 (n = 39) showed an ORR of 42.7% (95% CI, 33.6%-52.2%), a complete response (CR) rate of 4.3%, and a partial response (PR) rate of 38.5%. The disease control rate (DCR) was 86.3% (95% CI, 78.7%-92.0%).
Additional data from the pooled analysis showed a median duration of response (DOR) of 7.0 months (95% CI, 4.2-9.8). The median progression-free survival (PFS) was 5.8 months (95% CI, 5.4-8.2), and the median overall survival (OS) was 15.6 months (95% CI, 13.1-19.0).
Safety Profile
Safety data from TROPION-Lung05 (n = 137) showed that all patients experienced at least one treatment-emergent adverse effect (TEAE), with 47% experiencing grade 3 or higher TEAEs. Treatment-related TEAEs of any grade occurred in 94% of patients, and grade 3 or higher events occurred in 29%. Serious adverse events of any grade were reported in 25% of patients.
Expert Commentary
Susan Galbraith, executive vice president of Oncology R&D at AstraZeneca, stated, "TROPION-Lung01 has also provided exciting exploratory data supporting our biomarker development, which will be validated in ongoing and planned phase 3 lung cancer trials."
Galbraith also noted regarding the breakthrough therapy designation, "This breakthrough therapy designation reinforces Dato-DXd as a promising potential therapy for patients with EGFR (search)-mutated lung cancer who continue to face significant unmet needs following disease progression on or after initial treatments."