Datroway (datopotamab deruxtecan-dlnk) / Daiichi Sankyo, AstraZeneca - LARVOL DELTA

Antibody-Drug Conjugates Versus Docetaxel for Previously Treated Advanced NSCLC: Systematic Review and Meta-Analysis of RCTs (IASLC-WCLC 2025) - "Methods : Databases [PubMed (MEDLINE), EMBASE and Cochrane Library], clinical trial registries, and proceedings of global oncology conferences from January 2015 to November 2024 were screened for phase II/III RCTs comparing ADC (e.g., sacituzumab govitecan, datopotamab deruxtecan, and tusamitamab ravtansine) versus docetaxel. Conclusions : Our findings report a significant survival benefit in patients with non-squamous NSCLC treated with ADCs compared to docetaxel with a manageable safety profile. However, further research is needed to address heterogeneity, refine patient selection and obtain more mature survival data with predictive biomarkers."

IO biomarker • Metastases • Retrospective data • Review • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Solid Tumor

Datopotamab Deruxtecan in Patients With Active Brain Metastases of Non-Squamous NSCLC: The TUXEDO-5 Phase II Trial [WITHDRAWN] (IASLC-WCLC 2025) - No abstract available

Clinical • P2 data • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Solid Tumor

Single-Cell RNA Sequencing Reveals Subtype-Specific Resistance Mechanisms to TROP2-Targeted ADCs in Non-Small Cell Lung Cancer (IASLC-WCLC 2025) - "The currently available TROP2-targeted ADCs, sacituzumab govitecan and datopotamab deruxtecan, have shown limited benefit in NSCLC overall, with relatively greater efficacy in lung adenocarcinoma (LUAD) compared to lung squamous cell carcinoma (LUSC), as seen in the TROPION-1 trial. These findings highlight the need to optimize ADC payload selection for improved efficacy in NSCLC, especially in LUSC. Further translational studies are warranted to validate these findings."

Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ABCC2 • SLFN11 • TACSTD2 • TOP1

Incidence and Severity of Interstitial Lung Disease Associated With Antibody-Drug Conjugates in NSCLC and SCLC: A Meta-Analysis (IASLC-WCLC 2025) - "In NSCLC, the highest pooled incidence of any-grade ILD was seen with patritumab deruxtecan (23%) and trastuzumab deruxtecan (22%), followed by datopotamab deruxtecan (9%), telisotuzumab vedotin (7%), and sacituzumab govitecan (1%)...Treatment discontinuation due to ILD in NSCLC was highest with telisotuzumab vedotin combined with erlotinib (36%), followed by trastuzumab deruxtecan (9%) and patritumab deruxtecan (7%)...In SCLC, any-grade ILD incidence was 8% with rovalpituzumab tesirine, with no reported grade ≥3 ILD events...HER2/HER3-targeted, deruxtecan-containing ADCs demonstrated the highest ILD rates, while other ADCs such as sacituzumab govitecan had minimal reported toxicity. These findings highlight the need for agent-specific ILD monitoring and support the consideration of ADC design, including target and payload, when evaluating pulmonary safety and guiding clinical decision-making."

Retrospective data • Interstitial Lung Disease • Lung Cancer • Non Small Cell Lung Cancer • Pulmonary Disease • Respiratory Diseases • Small Cell Lung Cancer • Solid Tumor • ERBB3 • HER-2

Intracranial Efficacy of Datopotamab Deruxtecan (Dato-DXd) in Patients With Advanced/Metastatic NSCLC in TROPION-Lung01 (IASLC-WCLC 2025) - P2, P3 | "Conclusions : In this retrospective analysis of TROPION-Lung01, Dato-DXd demonstrated intracranial activity and improved clinical benefit versus docetaxel in patients with baseline brain metastases, including those with untreated brain metastases or progression after radiotherapy. These findings were consistent with intracranial activity in the TROPION-Lung05 trial (NCT04484142), supporting the potential of Dato-DXd treatment in patients with NSCLC brain metastases."

Clinical • Metastases • CNS Disorders • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Solid Tumor • EGFR

Datopotamab deruxtecan induces hallmarks of immunogenic cell death. (PubMed, Cell Stress) - "Importantly, the TROP2-targeted ADC also exerted a bystander antitumor effect on parental U2OS cells (lacking TROP2 expression) co-cultured with TROP2-expressing U2OS cells. These findings demonstrate that datopotamab deruxtecan delivers a cytotoxic payload capable of inducing hallmark features of ICD in vitro."

Journal • Oncology • Osteosarcoma • Sarcoma • Solid Tumor • CALR • HMGB1 • TACSTD2

A Tale of Two TROP-2 ADCs: A Comparative Saga of Datopotamab Deruxtecan (Dato-DXd) and Sacituzumab Govitecan (SG). (PubMed, Oncologist) - No abstract available

Journal

LIBRA: A Study of Novel Combinations in Non-Small Cell Lung Cancer (NSCLC) (clinicaltrials.gov) - P2 | N=278 | Not yet recruiting | Sponsor: AstraZeneca

New P2 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Datroway: Regulatory decision in China for HR+, HER2 low 2L/3L breast cancer (based on TROPION-Breast01 trial) in H1 FY2025 (Daiichi Sankyo) - Q1 FY2025 Results

China approval • Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology

Datroway: Retrospective intracranial efficacy data from P3 TROPION-LUNG01 trial (NCT04656652) for 2L+ NSCLC at WCLC (Sep 6-9, 2025) (Daiichi Sankyo) - Q1 FY2025 Results: Data from P2 TROPION-PanTumor03 trial (NCT05489211) for urothelial cancer at ESMO (Oct 17-21, 2025)

P2 data • P3 data • Bladder Cancer • Genito-urinary Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Urothelial Cancer

Datroway + Keytruda: Data from P3 TROPION-Lung07 trial (NCT05555732) for 1L advanced or metastatic NSCLC in H1 2026 (AstraZeneca) - H1 & Q2 2025 Results

P3 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology

US expert Delphi consensus on the prevention and management of stomatitis in patients treated with datopotamab deruxtecan. (PubMed, Support Care Cancer) - "We used the expert consensus to provide guidelines for the prevention and management of stomatitis in patients treated with Dato-DXd."

Journal • Breast Cancer • Dental Disorders • Lung Cancer • Mucositis • Oncology • Solid Tumor • Stomatitis

Preclinical pharmacokinetic, pharmacodynamic, and safety profile of OBI-992: a novel TROP2-targeted antibody-drug conjugate. (PubMed, Mol Cancer Ther) - P1/2 | "The stability, pharmacokinetics, pharmacodynamics, and off-target toxicity of OBI-992 were evaluated and compared with a benchmark ADC datopotamab deruxtecan (Dato-DXd)...Major toxicities were target-related skin lesions and reduced reticulocytes, which were reversible during recovery period. These results support further clinical development of OBI-992 for the treatment of TROP2-expressing cancers, which it is currently in Phase 1 clinical trial (NCT06480240)."

Journal • PK/PD data • Preclinical • Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • TACSTD2 • TOP1

Datopotamab deruxtecan (Dato-DXd) + rilvegostomig (rilve) in patients (pts) with locally advanced or metastatic urothelial cancer (a/mUC): Results from the phase 2 TROPION-PanTumor03 study (ESMO 2025) - No abstract available

Clinical • Metastases • P2 data • Pan tumor • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer

Phase 1b Study of Valemetostat in Combination With Datopotamab Deruxtecan (Dato-DXd) in Advanced Non-Squamous Non-Small-Cell Lung Cancer (NSCLC): Initial Safety Results (ESMO 2025) - No abstract available

Clinical • Combination therapy • Metastases • P1 data • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Datopotamab deruxtecan (Dato-DXd) + durvalumab (D) as first-line (1L) treatment (tx) for unresectable locally advanced/metastatic triple-negative breast cancer (a/mTNBC): Final results from the phase 1b/2 BEGONIA study (ESMO 2025) - No abstract available

Clinical • Metastases • P1/2 data • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

Revolutionizing breast cancer treatment: the promise of antibody-drug conjugates. (PubMed, Clin Adv Hematol Oncol) - "Currently, 4 ADCs-sacituzumab govitecan, trastuzumab deruxtecan, trastuzumab emtansine, and the more-recent datopotamab deruxtecan-are approved for clinical application, with several others in advanced stages of development. Additionally, biomarker-driven strategies to identify those patients most likely to benefit from ADC therapy will support more personalized approaches to treatment. This review explores the structural and mechanistic features of ADCs in breast cancer, highlighting their therapeutic potential, and discusses ongoing clinical trials exploring new-generation ADCs and combination therapies."

Journal • Review • Breast Cancer • Oncology • Solid Tumor

Toxicity Profiles of Antibody-Drug Conjugates: Synthesis and Graphical Insights to Optimize Patient-Centered Treatment Strategies for HER2-Negative Metastatic Breast Cancer. (PubMed, Cancers (Basel)) - "The choice between ADCs in HER2-negative metastatic BC when both T-DXd and SG are treatment options should consider toxicity profiles to optimize patient-centered treatment strategies. Tailoring ADC selection based on individual tolerance and preferences is critical for shared decision-making, and future research should focus on assessing the utility and acceptability of such clinical tools to guide treatment selection."

Journal • Breast Cancer • Fatigue • Hematological Disorders • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Neutropenia • Oncology • Pneumonia • Solid Tumor • HER-2

Antibody-drug conjugates for treating early-stage breast cancer: current use, anticipated evolutions. (PubMed, NPJ Breast Cancer) - "After improving outcomes for patients with metastatic disease, ADC testing moved to the curative setting, where already one agent (trastuzumab emtansine) has been approved, after demonstrating to improve overall survival. Herein, we review the rationale, evidence, and challenges with the use of ADCs in the early-stage setting."

Journal • Review • Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

Datroway + Imfinzi: Data from P3 AVANZAR trial (NCT05687266) for 1L NSCLC in H1 2026 (AstraZeneca) - H1 & Q2 2025 Results

P3 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology

Datroway: Data from P2 TROPION-PanTumor03 trial (NCT05489211) for advanced solid tumors post 2026 (AstraZeneca) - H1 & Q2 2025 Results: Data from P1 TROPION-PanTumor01 trial (NCT03401385) for solid tumors in H2 2025

P1 data • P2 data • Oncology • Solid Tumor

Datroway: Data from P3 TROPION-Lung15 trial (NCT06417814) for locally advanced or metastatic NSCLC in H2 2026 (AstraZeneca) - H1 & Q2 2025 Results: Data from P1 TROPION-Lung04 trial (NCT04612751) for advanced or metastatic NSCLC in H1 2026

P1 data • P3 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology

Datroway: Data from P3 TROPION-Lung12 trial (NCT06564844) for stage I NSCLC post 2026 (AstraZeneca) - H1 Q2 2025 Results: Data from P3 TROPION-Lung14 trial (NCT06350097) for locally advanced or metastatic NSCLC post 2026

P3 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology

Datroway: Data from P3 TROPION-Breast05 trial (NCT06103864) for PD-L1-positive locally recurrent inoperable or metastatic TNBC post 2026 (AstraZeneca) - H1 & Q2 2025 Results: Data from P3 TROPION-Lung08 trial (NCT05215340) for advanced or metastatic NSCLC in H1 2026

P3 data • Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Triple Negative Breast Cancer

Datroway: Data from P3 TROPION-Breast02 trial (NCT05374512) for 1L TNBC in H2 2025 (AstraZeneca) - H1 & Q2 2025 Results: Data from P3 TROPION-Breast04 trial (NCT06112379) for early stage TNBC post 2026

P3 data • Breast Cancer • Oncology • Triple Negative Breast Cancer