Investigational Drug
Datopotamab deruxtecan
TrialFetch AI Analysis
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Overview
Datopotamab deruxtecan (Dato-DXd; DS-1062; marketed as Datroway) is a TROP2-directed antibody–drug conjugate developed for solid tumors. It is no longer solely investigational: in the United States it is approved for selected patients with HR-positive/HER2-negative or triple-negative breast cancer and, under accelerated approval, previously treated EGFR-mutated non-small-cell lung cancer (NSCLC). Studies in other disease settings and treatment combinations remain ongoing. (fda.gov)
Mechanism of action
Dato-DXd comprises a humanized anti-TROP2 IgG1 antibody connected through a cleavable linker to DXd, a potent exatecan-derived topoisomerase-I inhibitor. After binding TROP2 and internalization, lysosomal processing releases DXd, causing DNA damage and apoptosis. Preclinical evidence also supports a bystander effect against neighboring cells and induction of features associated with immunogenic cell death. (pmc.ncbi.nlm.nih.gov)
Efficacy
- Previously treated HR-positive/HER2-negative breast cancer: In the randomized phase III TROPION-Breast01 trial (732 patients), Dato-DXd improved progression-free survival versus investigator-selected chemotherapy (hazard ratio 0.63). Objective response rates were 36.4% versus 22.9%, with median response durations of 6.7 and 5.7 months, respectively. Overall-survival data were immature in the primary publication. (ascopubs.org)
- Previously untreated advanced triple-negative breast cancer unsuitable for immunotherapy: In phase III TROPION-Breast02 (644 patients), median progression-free survival was 10.8 versus 5.6 months, median overall survival was 23.7 versus 18.7 months, and objective response rates were approximately 63–64% versus 29–30% for Dato-DXd and chemotherapy, respectively. (sciencedirect.com)
- Previously treated advanced NSCLC: In phase III TROPION-Lung01, median progression-free survival was 4.4 versus 3.7 months with Dato-DXd and docetaxel, while overall survival did not differ significantly. Benefit was concentrated in the prespecified nonsquamous subgroup; outcomes did not favor Dato-DXd in squamous disease. (pubmed.ncbi.nlm.nih.gov)
- Previously treated EGFR-mutated NSCLC: A pooled FDA analysis of 114 patients from TROPION-Lung05 and TROPION-Lung01 found an objective response rate of 45% and median response duration of 6.5 months, supporting accelerated approval. (fda.gov)
Safety
The characteristic toxicities include stomatitis/oral mucositis, nausea, ocular-surface reactions, alopecia and fatigue. Interstitial lung disease/pneumonitis is an important, potentially fatal risk requiring monitoring and treatment interruption when suspected. (pubmed.ncbi.nlm.nih.gov)
In TROPION-Breast01, grade 3 or higher treatment-related adverse events occurred in 20.8% with Dato-DXd versus 44.7% with chemotherapy; treatment-related oral mucositis/stomatitis occurred in 57.2%, ocular-surface events in 43.9%, and adjudicated drug-related pneumonitis in 3.9%, including one fatal event. In TROPION-Lung01, grade 3 or higher treatment-related events occurred in 25.6% versus 42.1% with docetaxel, while drug-related pneumonitis was more frequent with Dato-DXd (8.8% versus 4.1%). (ascopubs.org)
Further reading
- TROPION-Breast01 phase III results
- TROPION-Breast02 phase III results
- TROPION-Lung01 phase III results
- TROPION-Lung05 phase II results
- Preclinical mechanism and pharmacology
- FDA approval information
Last updated: Sep 2026
Active trials using Datopotamab deruxtecan
Found 14 active trials using this drug:
TrialFetch AI summary: Adults with metastatic NSCLC harboring an osimertinib-sensitive EGFR mutation who have progressed after a third-generation EGFR TKI and received platinum chemotherapy or are ineligible for it receive ivonescimab, a PD-1/VEGF-A bispecific antibody, plus either datopotamab deruxtecan, a TROP2-directed topoisomerase I inhibitor antibody–drug conjugate, or osimertinib.
ClinicalTrials.gov ID: NCT07535437
TrialFetch AI summary: For patients with TROP2-positive stage IIIB–IV nonsquamous NSCLC without actionable genomic alterations whose disease has progressed after platinum chemotherapy and anti-PD-1/PD-L1 therapy, this study compares datopotamab deruxtecan with docetaxel. Datopotamab deruxtecan is a TROP2-directed antibody–drug conjugate that delivers a topoisomerase I inhibitor.
ClinicalTrials.gov ID: NCT07291037
TrialFetch AI summary: This single-arm study enrolls adults with endocrine-refractory, HR-positive, HER2 IHC 0 inoperable locally advanced or metastatic breast cancer who have not received chemotherapy for metastatic disease. Patients receive datopotamab deruxtecan, a TROP2-directed antibody–drug conjugate that delivers a topoisomerase I inhibitor, before chemotherapy.
ClinicalTrials.gov ID: NCT07205822
TrialFetch AI summary: Adults with unresectable locally advanced or metastatic urothelial carcinoma that progressed during or after first-line enfortumab vedotin plus pembrolizumab, and who are eligible for cisplatin or carboplatin, receive datopotamab deruxtecan plus platinum or gemcitabine plus platinum. Datopotamab deruxtecan is a TROP2-directed antibody–drug conjugate that delivers a topoisomerase I inhibitor.
ClinicalTrials.gov ID: NCT07129993
TrialFetch AI summary: Adults with locally advanced or metastatic NSCLC and ECOG 0–1 are enrolled in first-line cohorts without known actionable alterations (PD-L1 ≥1%) or a second-line nonsquamous cohort with actionable alterations after progression on targeted therapy. First-line treatment is rilvegostomig (a PD-1/TIGIT bispecific antibody) with or without ramucirumab (anti-VEGFR2), depending on PD-L1 expression; second-line treatment is datopotamab deruxtecan (a TROP2-directed, topoisomerase I inhibitor–delivering antibody–drug conjugate) plus ramucirumab, with or without rilvegostomig.
ClinicalTrials.gov ID: NCT07098338
TrialFetch AI summary: Adults with unresectable locally advanced or metastatic HER2-low or HER2-0 breast cancer, including hormone receptor–positive and –negative disease, receive trastuzumab deruxtecan (HER2-directed) or datopotamab deruxtecan (TROP2-directed), both antibody–drug conjugates carrying topoisomerase I inhibitors. Eligible patients may receive the other agent after progression, including those who enter having already progressed on one of the two drugs.
ClinicalTrials.gov ID: NCT06533826
TrialFetch AI summary: For patients with EGFR-mutated, locally advanced or metastatic nonsquamous NSCLC with extracranial progression on osimertinib and no prior non-EGFR-TKI systemic therapy for metastatic disease, this trial compares datopotamab deruxtecan (Dato-DXd) alone or with continued osimertinib against platinum–pemetrexed chemotherapy. Dato-DXd is a TROP2-directed antibody–drug conjugate that delivers a topoisomerase I inhibitor.
ClinicalTrials.gov ID: NCT06417814
TrialFetch AI summary: Adults with previously untreated, unresectable locally advanced, metastatic, or recurrent nonsquamous NSCLC harboring an EGFR exon 19 deletion or L858R mutation are randomised to first-line osimertinib alone or with datopotamab deruxtecan. Datopotamab deruxtecan is a TROP2-directed antibody–drug conjugate that delivers a topoisomerase I inhibitor.
ClinicalTrials.gov ID: NCT06350097
TrialFetch AI summary: Adults with previously untreated, unresectable stage IIIB/IIIC or metastatic non-squamous NSCLC, PD-L1 expression ≥50%, no actionable genomic alteration, and ECOG 0–1 are randomized to datopotamab deruxtecan plus rilvegostomig, rilvegostomig alone, or pembrolizumab alone. Datopotamab deruxtecan is a TROP2-directed antibody–drug conjugate carrying a topoisomerase I inhibitor; rilvegostomig is a bispecific PD-1/TIGIT antibody.
ClinicalTrials.gov ID: NCT06357533
TrialFetch AI summary: Adults with HER2-negative metastatic breast cancer and ECOG 0–2 are eligible if they have ER-positive brain metastases after endocrine therapy, triple-negative brain metastases, or leptomeningeal disease of any ER status. All receive datopotamab deruxtecan, a TROP2-directed antibody–drug conjugate that delivers a topoisomerase I inhibitor, every 21 days; there is no comparator arm.
ClinicalTrials.gov ID: NCT06176261
TrialFetch AI summary: For patients with PD-L1–positive (CPS ≥10), inoperable locally recurrent or metastatic triple-negative breast cancer who have received no systemic therapy for advanced disease, this trial compares datopotamab deruxtecan (Dato-DXd) plus durvalumab, Dato-DXd alone, and chemotherapy plus pembrolizumab. Dato-DXd is a TROP2-directed antibody–drug conjugate delivering a topoisomerase I inhibitor; durvalumab and pembrolizumab are immune checkpoint inhibitors.
ClinicalTrials.gov ID: NCT06103864
TrialFetch AI summary: Adults with advanced or metastatic endometrial, gastric, castration-resistant prostate, ovarian, colorectal, urothelial, or biliary tract cancer receive datopotamab deruxtecan, a TROP2-directed antibody–drug conjugate delivering a topoisomerase I inhibitor, either alone or in tumor-specific combinations. Combination partners include fluoropyrimidines, platinum chemotherapy, bevacizumab, corticosteroids, or the investigational bispecific antibodies volrustomig (PD-1/CTLA-4) and rilvegostomig (PD-1/TIGIT).
ClinicalTrials.gov ID: NCT05489211
TrialFetch AI summary: Patients with advanced solid tumors are enrolled in biomarker- and tumor-specific cohorts, including homologous-recombination-repair–mutated breast, ovarian, pancreatic or castration-resistant prostate cancer; recurrent IDH-mutant glioma; HER2-expressing or HER2-mutant tumors; and previously treated triple-negative breast, endometrial, ovarian or prostate cancer. They receive the brain-penetrant, PARP1-selective inhibitor palacaparib (AZD9574) alone or with temozolomide, the HER2-directed antibody–drug conjugate trastuzumab deruxtecan, or the TROP2-directed antibody–drug conjugate datopotamab deruxtecan.
ClinicalTrials.gov ID: NCT05417594
TrialFetch AI summary: Adults with previously untreated, unresectable stage IIIB/IIIC or stage IV nonsquamous NSCLC, PD-L1 TPS ≥50%, and no actionable genomic alterations are randomized to pembrolizumab plus datopotamab deruxtecan or pembrolizumab alone. Datopotamab deruxtecan is a TROP2-directed antibody–drug conjugate that delivers a topoisomerase I inhibitor.
ClinicalTrials.gov ID: NCT05215340
