Dato-DXd Earns FDA Accelerated Approval in Pretreated EGFR-Mutated mNSCLC

Data from the TROPION-Lung05 and TROPION-Lung01 trials support the FDA approval of dato-DXd in this NSCLC population.

The News

The FDA has granted accelerated approval to datopotamab deruxtecan (dato-DXd; Datroway) as a treatment for patients with pretreated EGFR-mutant metastatic non–small cell lung cancer (NSCLC), according to a press release from the agency.1

Supporting Data

The approval for dato-DXd was supported by findings from 2 clinical trials: the phase 2 TROPION-Lung05 trial (NCT04484142) and the phase 3 TROPION-Lung01 trial (NCT04656652).

Efficacy was evaluated in a pooled subgroup analysis of the TROPION-Lung05 and TROPION-Lung01 trials composed of 114 patients with locally advanced/metastatic EGFR-mutated NSCLC who had received prior EGFR-directed therapy and platinum-based chemotherapy. Data from the pooled analysis revealed that the objective response rate (ORR) was 45% (95% CI, 35%-54%) with Dato-DXd; the median duration of response (DOR) was 6.5 months (95% CI, 4.2-8.4).

Results from the phase 2 TROPION-Lung05 trial published in the Journal of Clinical Oncology revealed that among 137 patients given 6 mg/kg of dato-DXd every 21 days for pretreated NSCLC, the confirmed ORR was 35.8% (95% CI, 27.8%-44.4%), including 32.8% of patients experiencing a partial response and 2.9% having a complete response.2 Additionally, among those with EGFR-mutant disease, the confirmed ORR was 43.6%, with a disease control rate (DCR) of 82.1% and a median DOR of 7.0 months.

Additionally, data from the phase 3 TROPION-Lung01 trial published in the Journal of Clinical Oncology revealed that dato-DXd showed a progression-free survival (PFS) advantage vs docetaxel, at a median of 4.4 months (95% CI, 4.2-5.6) vs 3.7 months (95% CI, 2.9-4.2), respectively (HR, 0.75; 95% CI, 0.62-0.91; P = .004).3 The median overall survival was 12.9 months (95% CI, 11.0-13.9) vs 11.8 months (95% CI, 10.1-12.8), respectively (HR, 0.94; 95% CI, 0.78-1.14; P = .530).

Adverse Effects

In the phase 2 TROPION-Lung05 trial, treatment-related adverse effects (TRAEs) of grade 3 or higher were observed in 28.5% of patients, and the most common included stomatitis (9.5%), nausea (2.2%), and decreased appetite (2.2%). Two fatal AEs were reported, including 1 due to dyspnea and another due to NSCLC progression; neither death was attributable to study drug.

Furthermore, the incidence of grade 3 or higher TRAEs was 25.6% among those who received dato-DXd vs 42.1% in patients who received paclitaxel in TROPION-Lung01.

The recommended dato-DXd dose is 6 mg/kg, with a maximum of 540 mg for patients with a weight of 90 kg or greater. Treatment is recommended as an intravenous infusion once every 3 weeks until progression or unacceptable toxicity.

The FDA previously granted dato-DXd priority review in pretreated EGFR-mutant metastatic NSCLC in January 2025.4

References

1. FDA grants accelerated approval to datopotamab deruxtecan-dlnk for EGFR-mutated non-small cell lung cancer. News release. FDA. June 23, 2025. Accessed June 23, 2025. https://tinyurl.com/mtay7ab9
2. Sands J, Ahn MJ, Lisberg A, et al. Datopotamab deruxtecan in advanced or metastatic non-small cell lung cancer with actionable genomic alterations: results from the phase II TROPION-Lung05 study. J Clin Oncol. Published online January 6, 2025. doi:10.1200/JCO-24-01349
3. Ahn MJ, Tanaka K, Paz-Ares L, et al. Datopotamab deruxtecan versus docetaxel for previously treated advanced or metastatic non-small cell lung cancer: the randomized, open-label phase III TROPION-Lung01 study. J Clin Oncol. Published online September 9, 2024. doi:10.1200/JCO-24-01544
4. Datopotamab deruxtecan granted priority review in the U.S. for patients with previously treated advanced EGFR-mutated non-small cell lung cancer. News release. Daiichi-Sankyo. January 13, 2025. Accessed June 23, 2025. https://tinyurl.com/3797ayww