FDA Approves Datopotamab Deruxtecan for EGFR-Mutated NSCLC

Today, the FDA granted accelerated approval to datopotamab deruxtecan-dlnk (Datroway; Daiichi Sankyo Inc) for the treatment of adults with locally advanced or metastatic EGFR-mutated non–small cell lung cancer (NSCLC) who have previously received EGFR-directed therapy and platinum-based chemotherapy.¹

The approval was based on efficacy data pooled from 2 clinical trials: TROPION-Lung05 (NCT04484142), a multicenter, single-arm study, and TROPION-Lung01 (NCT04656652), a multicenter, open-label, randomized controlled trial. Together, these studies evaluated 114 patients who had received prior EGFR-directed therapy and platinum-based chemotherapy and were treated with datopotamab deruxtecan at the recommended dose. According to a blinded independent central review using RECIST v1.1 criteria, the confirmed overall response rate was 45% (95% CI, 35%-54%), and the median duration of response was 6.5 months (95% CI, 4.2-8.4), indicating meaningful clinical activity in a difficult-to-treat group of patients.

Datopotamab deruxtecan is administered as an intravenous infusion at a recommended dose of 6 mg/kg every 3 weeks, up to a maximum of 540 mg for patients weighing 90 kg or more. Treatment should continue until disease progression or unacceptable toxicity. The drug’s prescribing information includes warnings and precautions for serious adverse events, including interstitial lung disease/pneumonitis, ocular adverse reactions, stomatitis, and embryo-fetal toxicity.

Earlier this year, datopotamab deruxtecan received FDA approval for the treatment of adult patients with unresectable or metastatic/HR-positive, HER2-negative breast cancer who had received prior endocrine-based therapy and chemotherapy.² The approval was based on results from the phase 3 TROPION-Breast01 (NCT05104866) trial, which demonstrated a statistically significant improvement in progression-free survival (6.9 vs 4.9 months; HR, 0.63; P < .0001) and a higher confirmed objective response rate (36% vs 23%) compared with standard chemotherapy.

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://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-datopotamab-deruxtecan-dlnk-egfr-mutated-non-small-cell-lung-cancer
2. Steinzor P. FDA approves datopotamab deruxtecan for HR-positive/HER2-negative metastatic breast cancer. AJMC^®. January 17, 2025. Accessed June 23, 2025. https://www.ajmc.com/view/fda-approves-datopotamab-deruxtecan-for-hr-positive-her2-negative-metastatic-breast-cancer