A Pooled Analysis of Datopotamab Deruxtecan in Patients With EGFR-Mutated NSCLC.

Background: This exploratory analysis assessed datopotamab deruxtecan (Dato-DXd) in pretreated patients with advanced or metastatic NSCLC and EGFR mutations.

Methods: Data were pooled from the phase II TROPION-Lung05 (NCT04484142) and phase III TROPION-Lung01 (NCT04656652) trials. Patients with EGFR-mutated advanced or metastatic NSCLC, who had received previous targeted therapies and platinum-based chemotherapy, received Dato-DXd 6 mg/kg (TROPION-Lung05) or were randomized to Dato-DXd 6 mg/kg or docetaxel 75 mg/m² (TROPION-Lung01) once every 3 weeks. End points included objective response rate, duration of response, and progression-free survival, all per blinded independent central review, overall survival, and safety.

Results: In total, 117 patients with EGFR mutations who received Dato-DXd were included in the pool. The population was heavily pretreated (median three lines of previous therapies; range, 1-5) and predominantly Asian (69%). The most common mutations were exon 19 deletion (51%), L858R (32%), and T790M (27%); more than one EGFR mutation could be present. The confirmed objective response rate was 43% (95% confidence interval [CI]: 34-52), including five complete responses (4%). Median duration of response was 7.0 months (95% CI: 4.2-9.8). Median progression-free survival and overall survival were 5.8 (95% CI: 5.4-8.2) and 15.6 months (95% CI: 13.1-19.0), respectively. The safety profile of Dato-DXd was consistent with the individual studies. No new safety signals were observed. Rates of grade greater than or equal to 3 treatment-related adverse events and serious adverse events were 23% and 6%, respectively.

Conclusion: Dato-DXd demonstrated meaningful clinical activity in patients with EGFR-mutated advanced or metastatic NSCLC who had progressed on EGFR-directed therapies and chemotherapy, with an acceptable safety profile.