Initial US Approval

  • 20241

Indications

  • Adult patients 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. (This indication is approved under accelerated approval based on objective response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trial).1
  • Adult patients with unresectable or metastatic, hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative (IHC 0, IHC 1+ or IHC 2+/ISH-) breast cancer who have received prior endocrine-based therapy and chemotherapy for unresectable or metastatic disease.1

Recommended Dose/Route

  • Datopotamab deruxtecan(Dato-DXd) 6 mg/kg (up to a maximum of 540 mg for patients ≥90 kg) administered as an intravenous infusion once every 3 weeks (21-day cycle) until disease progression or unacceptable toxicity.1
  • Ophthalmic exams should be conducted at treatment initiation and annually thereafter.1
  • Administer Dato-DXd with recommended premedications and concomitant medications (see DATROWAY prescribing information).1
Figure

Pivotal Studies

TROPION-Lung052

  • Key Inclusion Criteria: Patients with EGFR-mutant, locally advanced or metastatic NSCLC who experienced disease progression following prior osimertinib therapy; no prior chemotherapy in the advanced/metastatic setting; ECOG 0–1; measurable disease by RECIST 1.1.
  • Treatment: Patients received either Dato-DXd (6 mg/kg IV every 3 weeks) in combination with osimertinib (80 mg orally once daily) or platinum-based chemotherapy (eg, cisplatin or carboplatin + pemetrexed), based on randomization arm.

TROPION-Lung013

  • Key Inclusion Criteria: Adults (≥18 years) with histologically or cytologically confirmed advanced or metastatic NSCLC (nonsquamous or squamous) who have received prior platinum-based chemotherapy with or without immunotherapy; measurable disease per RECIST 1.1; ECOG performance status 0–1; and adequate organ function.
  • Treatment: Patients received Dato-DXd; 6 mg/kg IV every 3 weeks or docetaxel 75 mg/m² IV every 3 weeksuntil disease progression or unacceptable toxicity.

TROPION-PanTumor014

  • Key Inclusion Criteria: Adults with advanced or metastatic epithelial tumors (including NSCLC) that are TROP2-expressing, and who have progressed on standard therapies; ECOG 0–1; measurable disease per RECIST 1.1; archival or fresh tissue available for biomarker assessment.
  • Treatment: Patients received datopotamab deruxtecan (Dato-DXd; dose based on tumor type and protocol cohort, commonly 6 mg/kg IV every 3 weeks) as monotherapy across multiple solid tumor types, including NSCLC, breast, and others.
Figure

Safety 

TROPION-Lung05, TROPION-Lung01, and TROPION-PanTumor011-5

  • Common Adverse Reactions (≥10%): The most frequently reported any-grade adverse events (AE) were stomatitis (71%), nausea (50%), alopecia (49%), fatigue (42%) constipation (31%), musculoskeletal pain (22%), rash (20%), decreased appetite (20%), cough (18%), vomiting (16%), dry eye (13%), infusion-related reaction (13%), headache (13%), diarrhea (12%), keratitits (12%), pruritits (12%), and dyspnea (11%).
  • Common Laboratory Abnormalities (≥10%): The most frequently reported any-grade laboratory abnormalities weredecreased hemoglobin (34%), decreased lymphocytes (32%), increased calcium (31%), increased aspartate aminotransferase (28%), decreased white blood cell count (27%), increased lactate dehydrogenase (23%), and increased alanine aminotransferase (20%).
  • Dosage Interruption Due toAEs: 43%
  • Dosage Reductions Due to AEs: 26%
  • Permanent Discontinuation Due to AEs: 8%
Figure

References

  1. DATROWAY (datopotamabderuxtecan-dlnk). Prescribing information. DaiichiSankyo, Inc; 2025. AccessedJune 26, 2025. https://daiichisankyo.us/prescribing-information-portlet/getPIContent?productName=Datroway&inline=true
  2. Sands J, Ahn MJ, Lisberg A, et al. Datopotamabderuxtecan in advanced or metastatic non-small cell lung cancer with actionable genomic alterations: results from the phase II TROPION-Lung05 study. J Clin Oncol. 2025;43(10):1254-1265. doi:10.1200/JCO-24-01349
  3. Ahn MJ, Tanaka K, Paz-Ares L, et al. Datopotamabderuxtecan 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. 2025;43(3):260-272. doi:10.1200/JCO-24-01544
  4. Sun Y, Xiao Z, Cheng Y, et al. Datopotamabderuxtecan (Dato-DXd) in Chinese patients (pts) with advanced or metastatic non-small cell lung cancer (NSCLC): Results from the phase 1/2 TROPION-PanTumor02 study. J Clin Oncol. 2024;42(16):8548.doi:10.1200/JCO.2024.42.16_suppl.8548
  5. Ahn MJ, Sands J, Lisberg AE, et al. Efficacy and safety of datopotamabderuxtecan (Dato-DXd) in patients (pts) with previously-treated EGFR-mutated advanced non-small cell lung cancer (NSCLC): A pooled analysis of TROPION-Lung01 and TROPION-Lung05. Ann of Oncol. 2024;35:S1630-S1631. doi:10.1016/j.annonc.2024.10.656