Database for
Therapeutic Antibodies
Therapeutic Antibodies
| Entry ID | 1723 |
| INN | Datopotamab deruxtecan |
| Status | Approved |
| Drug code(s) | DS-1062, Dato-DXd |
| Brand name | DATROWAY® |
| mAb sequence source | mAb humanized |
| General Molecular Category | ADC |
| Format, general category | Full length Ab conjugate |
| Format details | None |
| Isotype (Fc) | IgG1 |
| Light chain isotype | kappa |
| Linker | Glycine-Glycine-Phenylalanine-Glycine (GGFG; Tetrapeptide-based cleavable linker) |
| Ave. DAR | 4 |
| Conjugated/fused moiety | Topoisomerase I inhibitor, DXd/DX-8951 (MAAA-1181a) |
| Discovery method/technology | None |
| Target(s) | TROP-2 |
| Indications of clinical studies | Breast cancer, Advanced or Metastatic Non-Small Cell Lung Cancer With Actionable Genomic Alterations, Solid tumors |
| Primary therapeutic area | Cancer |
| Most advanced stage of development (global) | Approved US, Japan |
| Status | Active |
| Start of clinical phase (IND filing or first Phase 1) | January 31, 2018 |
| Start of Phase 2 | |
| Start of Phase 3 | December 15, 2020 |
| Date BLA/NDA submitted to FDA | |
| Year of first approval (global) | 2024 |
| Date of first US approval | January 17, 2025 |
| INN, US product name | Datopotamab deruxtecan, Datopotamab deruxtecan-dlnk |
| US or EU approved indications | US: First approval for Breast Cancer (DATROWAY is indicated for the treatment of 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) [as of January 17, 2025 label] |
| Company | Daiichi Sankyo Co. Ltd |
| Licensee/Partner | AstraZeneca |
| Comments about company or candidate | January 2025: EMA issues positive opinion for breast cancer indication; MAA for non-squamous NSCLC withdrawn. January 17, 2025: the Food and Drug Administration approved datopotamab deruxtecan-dlnk (Datroway, Daiichi Sankyo, Inc.), a Trop-2-directed antibody and topoisomerase inhibitor conjugate, for adult patients with unresectable or metastatic, hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative (IHC 0, IHC1+ or IHC2+/ISH-) breast cancer who have received prior endocrine-based therapy and chemotherapy for unresectable or metastatic disease. Jan 13, 2025: AstraZeneca and Daiichi Sankyo’s Biologics License Application for datopotamab deruxtecan (Dato-DXd) has been accepted and granted Priority Review in the US for the treatment of adult patients with locally advanced or metastatic epidermal growth factor receptor-mutated (EGFRm) non-small cell lung cancer (NSCLC) who have received prior systemic therapies, including an EGFR-directed therapy. FDA action date for its regulatory decision, is anticipated during the third quarter of 2025. December 27, 2024 I Daiichi Sankyo’s DATROWAY® (datopotamab deruxtecan) has been approved in Japan for the treatment of adult patients with hormone receptor (HR) positive, HER2 negative (IHC 0, IHC 1+ or IHC 2+/ISH-) unresectable or recurrent breast cancer after prior chemotherapy. December 24, 2024 I Daiichi Sankyo and AstraZeneca have voluntarily withdrawn the marketing authorization application (MAA) in the EU for datopotamab deruxtecan (Dato-DXd) for the treatment of adult patients with locally advanced or metastatic nonsquamous non-small cell lung cancer (NSCLC) based on the TROPION-Lung01 phase 3 trial. Apr 2024: Biologics License Application (BLA) for datopotamab deruxtecan (Dato-DXd) has been accepted in the U.S. for the treatment of adult patients with unresectable or metastatic hormone receptor (HR) positive, HER2 negative (IHC 0, IHC 1+ or IHC 2+/ISH-) breast cancer who have received prior systemic therapy for unresectable or metastatic disease. The Prescription Drug User Fee Act (PDUFA) date, the U.S. Food and Drug Administration (FDA) action date for its regulatory decision, is January 29, 2025. https://www.astrazeneca.com/media-centre/press-releases/2024/fda-accepts-dato-dxd-bla-for-breast-cancer.html. Mar 5, 2024: The European Medicines Agency has validated two marketing authorization applications (MAA) for Daiichi Sankyo and AstraZeneca’s antibody-drug conjugate (ADC) datopotamab deruxtecan in two types of cancer. One MAA is for the treatment of adult patients with locally advanced or metastatic nonsquamous non-small cell lung cancer who require systemic therapy following prior treatment. The other MAA is for the treatment of adult patients with unresectable or metastatic hormone receptor positive, HER2 negative (IHC 0, IHC 1+ or IHC 2+/ISH-) breast cancer who have progressed on and are not suitable for endocrine therapy and received at least one additional systemic therapy. Feb 19, 2024: AstraZeneca and Daiichi Sankyo’s Biologics License Application (BLA) for datopotamab deruxtecan (Dato-DXd) has been accepted in the US for the treatment of adult patients with locally advanced or metastatic nonsquamous non-small cell lung cancer (NSCLC) who have received prior systemic therapy. The Prescription Drug User Fee Act date, the Food and Drug Administration (FDA) action date for its regulatory decision, is Dec 20, 2024. Phase 3 studies for Non-small cell lung cancer (NCT05555732, NCT05215340, NCT04656652, NCT05687266); Breast cancer (NCT05374512, NCT05104866, NCT05629585) are all recruiting as of Feb-May, 2023, except NCT05104866 for breast cancer which is active not recruiting as of March, 2023. AZ H1 2022 update: Expect regulatory submission for datopotamab deruxtecan TROPION-Lung01 2L+ NSCLC with and without actionable alterations in H1 2023. NCT05555732 Phase 3 in NSCLC due to start in Nov 2022. Four Phase 3 studies recruiting as of June 2022. NCT05104866 Phase 3 in breast cancer started in Oct 2021. Dec 14, 2020: Daiichi Sankyo Company, Limited and AstraZeneca announced the initiation of TROPION-Lung01, a global pivotal phase 3 head-to-head study of datopotamab deruxtecan (Dato-DXd; DS-1062), a TROP2 directed antibody drug conjugate (ADC), versus docetaxel in patients with advanced or metastatic non-small cell lung cancer (NSCLC) without actionable genomic alterations who have previously received platinum-based chemotherapy and immunotherapy. NCT04656652 Phase 3 in NSCLC not yet recruiting when first posted on Dec 7, 2020 July 2020: AstraZeneca has agreed to develop Daiichi Sankyo’s Phase I cancer antibody drug conjugate (ADC) DS-1062 worldwide except Japan, through a collaboration that the Japanese pharma said today could generate for it up to $6 billion—of which $1 billion will be paid within two years. NCT04484142 Phase 2 in NSCLC not yet recruiting when first posted on July 23, 2020 As of June 2020, Daiichi Sankyo anticipates to initiate a Phase II study of DS-1062 in NSCLC without mutations of dose A and B in the fourth quarter of fiscal year 2020. NCT03401385 First-in-human Study of DS-1062a for Advanced Solid Tumors; anti-TROP-2 antibody ADC. Initial results reported at ASCO in June 2019: DS-1062a was well tolerated at doses up to 2.0-mg/kg. An observable PR and multiple pts with SD warrant further evaluation of DS-1062a. The maximum tolerated dose has not been reached, and this study is ongoing.http://abstracts.asco.org/239/AbstView_239_256199.html |
| Full address of company | Chuo City, Tokyo, Japan Asia Japan https://www.daiichisankyo.com/ |
DS-1062 is a smart chemotherapy composed of a humanized anti-TROP2 monoclonal antibody attached to a novel topoisomerase I inhibitor payload by a tetrapeptide-based cleavable linker with a drug-to-antibody ratio (DAR) of four.
| Anticipated events | Review in the EU(?), China |
| Factor(s) contributing to discontinuation | None |