FDA Approves Datopotamab for Treatment of EGFR-Mutated Non-Small Cell Lung Cancer

Datopotamab deruxtecan-dlnk (Datroway, Daiichi Sankyo, Inc) received FDA approval for treatment of adults with locally advanced or metastatic epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) who have received prior EGFR-directed therapy and platinum-based chemotherapy. The decision is based on data from the TROPION-Lung05 (NCT04484142) and TROPION-Lung01 (NCT04656652) trials.^1,2

3D rendering of lung cancer screening x-ray | Image Credit: © Vector Market - stock.adobe.com

NSCLC is the most common type of lung cancer, accounting for approximately 80% of all cases. EGFR mutations are highly prevalent and occur in about 10% to 15% of lung adenocarcinomas, of which exon 19 deletion and exon 21 L858R are most frequently detected. Standard of care for these patients involves EGFR-targeting Tyrosine kinase inhibitors (TKIs), which have improved outcomes; however, many patients eventually experience disease progression and need subsequent treatment.^3.4

Datopotamab is a TROP-2 targeting antibody drug conjugate (ADC) comprised of a humanized anti-TROP2 IgG1 monoclonal antibody attached to a number of topoisomerase I inhibitor payloads via tetrapeptide-based cleavable linkers. In 2024, the FDA granted datopotamab a breakthrough therapy designation for patients with NSCLC based on data from the TROPION-Lung05 and TROPION-Lung01 trials that have since led to the agent’s accelerated approval.⁵

The global, multicenter, single-arm, open-label phase II trial TROPION-Lung05 assessed the safety and efficacy of datopotamab in patients with locally advanced or metastatic NSCLC with actionable genomic alterations who have advanced on at least one platinum-based chemotherapy regimen and at least 1 TKI, whereas TROPION-Lung01 is a multicenter, open-label, randomized controlled trial assessing the same population. The end points measured across the studies were overall response rate (ORR), duration of response (DOR), PFS, and safety. ORR and DOR were established by blinded independent central review in accordance with RECIST v1.1.^3,5

In a pooled subgroup of 114 patients, the investigators reported a median DOR of 6.5 months (95% CI: 4.2, 8.4) and an ORR of 45% (95% CI: 35, 54).⁵

The FDA’s decision marks another step in the continued evolution of care for patients with EGFR-mutated NSCLC who continue to progress beyond initial lines of therapy. Datopotamab represents the latest advancement in the treatment landscape for NSCLC, expanding and diversifying treatment options for patients who progress after prior therapies.

REFERENCES

1. Study of DS-1062a in advanced or metastatic non-small cell lung cancer with actionable genomic alterations (TROPION-Lung05). Updated June 3, 2025. Accessed June 23, 2025. https://clinicaltrials.gov/study/NCT04484142

2. Study of DS-1062a versus docetaxel in previously treated advanced or metastatic non-small cell lung cancer with or without actionable genomic alterations (TROPION-LUNG01). Updated March 30, 2025. Accessed June 23, 2025. https://clinicaltrials.gov/study/NCT04656652

3. Datopotamab deruxtecan granted breakthrough therapy designation in US for patients with previously treated advanced EGFR-mutated non-small cell lung cancer. AstraZeneca. December 9, 2024. Accessed June 23, 2025. https://www.astrazeneca.com/media-centre/press-releases/2024/datopotamab-deruxtecan-granted-breakthrough-therapy-designation-us-patients-previously-treated-advanced-egfr-mutated-non-small-cell-lung-cancer.html

4. Gerlach A. Navigating EGFR mutations and ALK fusions in early-stage non-small cell lung cancer. Pharmacy Times. June 19, 2025. Accessed June 23, 2025. https://www.pharmacytimes.com/view/navigating-egfr-mutations-and-alk-fusions-in-early-stage-non-small-cell-lung-cancer

5. FDA grants accelerated approval to datopotamab deruxtecan-dlnk for EGFR-mutated non-small cell lung cancer. 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?utm_medium=email&utm_source=govdelivery