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

Synergistic strategies: ADC-PARP inhibitor combinations in triple-negative breast cancer therapy. (PubMed, Pathol Res Pract) - "ADCs like sacituzumab govitecan (SG) and datopotamab deruxtecan (Dato-DXd) target cytotoxic payloads with specificity, whereas PARPis like olaparib, rucaparib, niraparib, and talazoparib cause synthetic lethality in homologous recombination repair (HRR)-deficient tumors. Future directions include biomarker-driven patient selection, combination with immune checkpoint inhibitors, and advancement in next-generation ADCs. The synergistic potential of ADC-PARPi combinations provides a new avenue for overcoming TNBC resistance, enhancing treatment outcomes, and widening therapeutic strategies for this challenging disease."

IO biomarker • Journal • Review • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • BRCA • HRD

A Study of Dato-DXd in Chinese Patients With Advanced Non-Small Cell Lung Cancer, Triple-negative Breast Cancer and Other Solid Tumors (TROPION-PanTumor02) (clinicaltrials.gov) - P1/2 | N=119 | Active, not recruiting | Sponsor: AstraZeneca | Trial completion date: Dec 2024 ➔ Dec 2025

Pan tumor • Trial completion date • Breast Cancer • Esophageal Cancer • Gastric Cancer • Genito-urinary Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • Urothelial Cancer • ALK • EGFR • HER-2 • PGR • ROS1

An evaluation of datopotamab deruxtecan for the treatment of non-small cell lung cancer. (PubMed, Expert Opin Biol Ther) - "however, patient selection remains paramount for future clinical development. Further research is necessary to optimize dosing strategies, manage adverse events, and better understand its role in both frontline and relapsed/refractory treatment settings as part of combination therapy, as well as neoadjuvant therapy prior to surgery."

Journal • Review • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

A pooled analysis of datopotamab deruxtecan in patients with EGFR-mutated NSCLC. (PubMed, J Thorac Oncol) - P2, P3 | "Dato-DXd demonstrated meaningful clinical activity in patients with EGFR-mutated advanced/metastatic NSCLC who had progressed on EGFR-directed therapies and chemotherapy, with an acceptable safety profile."

Journal • Retrospective data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

Efficacy and Safety of TROP-2-Targeting Antibody-Drug Conjugate Treatment in Previously Treated Patients with Advanced Non-Small Cell Lung Cancer: A Systematic Review and Pooled Analysis of Reconstructed Patient Data. (PubMed, Cancers (Basel)) - "The anti-TROP-2 regimen showed a better safety profile but failed to demonstrate a relevant clinical improvement over docetaxel. Anti-TROP-2 ADCs could find a role in the management of patients with AGAs."

Journal • Retrospective data • Review • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Multimodal cancer therapy consisting of antibody-drug conjugates and radiotherapy in cancer treatment (AACR 2025) - "Accordingly, combination of RT with ADCs targeting HER2: trastuzumab emtansine/deruxtecan/duocarmazine (T-DM1/T-DXd/T-Duo) and disitamab vedotin, TROP2: datopotamab deruxtecan and sacituzumab govitecan, EGFR: depatuxizumab MMAE, HER3: patritumab deruxtecan, Nectin4: enfortumab vedotin and CEACAM5: tusamitamab ravtansine were evaluated. Together, this study demonstrates that inherent sensitivity of tumor cells to different payload classes, DAR and TAA dynamic are of relevance for the efficacy of ADC. Informed selection of ADC exhibited synergistic effects with RT providing a novel multimodal and promising strategy for efficient cancer eradication."

Breast Cancer • Gastric Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • Squamous Cell Carcinoma • CEACAM5 • EGFR • ERBB3 • HER-2 • NECTIN4

A meta-analysis analyzing the efficacy and safety of datopotamab deruxtecan (Dato-DXd) in previously treated patients with non-small cell lung cancer (NSCLC). (ASCO 2025) - "Pooled data for Dato-DXd in the subsequent line setting demonstrated a robust overall response rate and disease control rate.In comparison DCR for docetaxel and ramucirumab in the REVEL study was 67%. Based on this, Dato-DXD could be a subsequent line treatment option in metastatic NSCLC. While meta-analysis results can be confounded by heterogeneity between studies, results of ongoing clinical studies on Dato-Dxd that may result in the near future may help better answer this question."

Retrospective data • Dental Disorders • Inflammation • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pneumonia • Solid Tumor • Stomatitis

Comparisons of survival outcomes of antibody-drug-conjugates in metastatic breast cancer: A network meta-analysis. (ASCO 2025) - " A total of 6449 patients from 12 RCTs of ADCs ado-trastuzumab emtansine (T-DM1), sacituzumab govitecan (SG), trastuzumab deruxtecan (T-DXd), and datopotamab deruxtecan (Dato-DXd) were included in the analysis. This network meta-analysis showed prominent survival benefits with ADC-containing regimens for mBC. Our results provide valuable insights into personalized treatment strategies for mBC patients."

Metastases • Retrospective data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor

Treatment-related toxicities of antibody-drug conjugates in breast cancer: A Bayesian network meta-analysis. (ASCO 2025) - " A total of 9307 patients in 17 RCTs of five different ADCs (ado-trastuzumab emtansine [T-DM1], sacituzumab govitecan [SG], trastuzumab deruxtecan [T-DXd], datopotamab deruxtecan [Dato-DXd], and ARX788) were included. This Bayesian network meta-analysis highlights significant variability in TRAEs among different ADCs in breast cancer therapy. T-DM1 was primarily associated with thrombocytopenia and hepatic toxicities, while SG and T-DXd were associated with neutropenia, anemia, GI disorders, and dermatological TRAEs. Our findings may help with selection of ADC therapies for patients with breast cancer, facilitating personalized approaches to minimize treatment-related toxicities."

Retrospective data • Alopecia • Anemia • Breast Cancer • CNS Disorders • Dermatology • Fatigue • Gastrointestinal Disorder • HER2 Breast Cancer • HER2 Positive Breast Cancer • Immunology • Musculoskeletal Diseases • Neutropenia • Oncology • Pruritus • Solid Tumor • Thrombocytopenia

DATO-Base: A phase II study of DATOpotamab deruxtecan for patients with breast cancer brain metastases or leptomeningeal disease. (ASCO 2025) - P2 | "In this setting, antibody-drug conjugates (ADCs) have shown promise, with impressive intracranial activity observed with trastuzumab deruxtecan. The trial was activated in December 2023, with enrollment ongoing. Clinical trial information: NCT06176261."

Clinical • P2 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Lung Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ER • HER-2

TROPION-Lung14: A phase 3 study of osimertinib ± datopotamab deruxtecan (Dato-DXd) as first-line (1L) treatment for patients with EGFR-mutated locally advanced or metastatic (LA/M) non-small cell lung cancer (NSCLC). (ASCO 2025) - P3 | "Overall survival is a key secondary endpoint; other secondary endpoints include PFS by investigator, objective response rate, duration of response, PFS2, safety, pharmacokinetics and immunogenicity. Enrollment is ongoing."

Clinical • Metastases • P3 data • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

First-line (1L) datopotamab deruxtecan (Dato-DXd) + rilvegostomig in advanced or metastatic non-small cell lung cancer (a/mNSCLC): Results from TROPION-Lung04 (cohort 5). (ASCO 2025) - P1 | "The safety profile for the combination of Dato-DXd + rilvegostomig was consistent with the expected toxicities of each agent and without new safety findings. Dato-DXd + rilvegostomig had encouraging activity as 1L treatment for pts with a/mNSCLC without AGAs, with responses seen in both histologies and across all PD-L1 levels."

Clinical • Metastases • Alopecia • Cardiovascular • Dental Disorders • Fatigue • Gastrointestinal Disorder • Immunology • Infectious Disease • Interstitial Lung Disease • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pneumonia • Pulmonary Disease • Respiratory Diseases • Septic Shock • Solid Tumor • Stomatitis • TIGIT

A meta-analysis of safety and efficacy of datopotamab deruxtecan and sacituzumab govitecan for second line treatment of metastatic non-small cell lung cancer (NSCLC). (ASCO 2025) - "Funded by No funding sources reported Background: Subsequent line treatment options for metastatic NSCLC remain limited. Direct comparisons between ADC (Dato-Dxd and SG) and docetaxel did not show a significant difference in disease progression or death rate. This study was limited by the small number of participants and heterogeneity of published literature as many clinical trials are still ongoing. Despite this, SG and Dato-DXd had a promising overall response rate of 67.6% and 76.5%, respectively."

Metastases • Retrospective data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

TROPION-Lung02: Datopotamab deruxtecan (Dato-DXd) plus pembrolizumab (pembro) with or without platinum chemotherapy (Pt-CT) as first-line (1L) therapy for advanced non-small cell lung cancer (aNSCLC). (ASCO 2025) - P1 | " Pts across 6 cohorts were dosed with Dato-DXd (4 or 6 mg/kg) plus pembro 200 mg alone (doublet) or with pembro plus Pt-CT (triplet; cisplatin 75 mg/m2 or carboplatin AUC 5) Q3W. In this largest data set to date evaluating an ADC combined with an anti-PD-1/L1 agent in the 1L setting, the combination of Dato-DXd plus pembro treatment both with and without Pt-CT elicited durable antitumor activity in pts with aNSCLC. Tolerability of the combinations was as expected, based on known profiles of the individual agents. aProportion of pts with confirmed CR + PR + SD at 12 wks."

Clinical • IO biomarker • Metastases • Dental Disorders • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Stomatitis • PD-L1

Neoadjuvant durvalumab (D) + chemotherapy (CT) + novel anticancer agents and adjuvant D ± novel agents in resectable non-small-cell lung cancer (NSCLC): Updated outcomes from NeoCOAST-2. (ASCO 2025) - P2 | " Pts were stratified by PD-L1 expression (<1% vs ≥1%) and randomized to neoadjuvant D + platinum-doublet CT + oleclumab (anti-CD73 monoclonal antibody [mAb]) then adjuvant D + oleclumab (Arm 1), neoadjuvant D + platinum-doublet CT + monalizumab (anti-NKG2A mAb) then adjuvant D + monalizumab (Arm 2), or neoadjuvant D + single-agent platinum CT + Dato-DXd (TROP2-directed antibody-drug conjugate [ADC]) then adjuvant D (Arm 4). All arms show that novel perioperative combinations may improve pCR rates and maintain tolerability and feasibility of surgery in resectable NSCLC. The final analysis of pCR and mPR rates in Arm 4 is the first for an ADC in this setting and confirms the encouraging efficacy and manageable safety profile of D + CT + Dato-DXd. Presurgical ctDNA clearance is associated with pathological responses."

Clinical • IO biomarker • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KLRC1

Datroway: "Results showed a numerically higher pCR rate in Arm 4 compared to current standard-of-care options and promising mPR rates"; Non small cell lung cancer (Daiichi Sankyo) - ASCO 2025: "The pCR and mPR rates in Arm 4 are the first reported for an antibody-drug conjugate in the neoadjuvant setting and confirm the encouraging efficacy and manageable safety profile of neoadjuvant durvalumab + Dato-DXd + Plt in this context"

P2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology

Datroway: "At TROPION-Lung02 final analysis, the combination of Dato-DXd + pembrolizumab ± Pt-CT continued to elicit durable antitumor activity in patients with a/mNSCLC, with efficacy observed in both high and low PD-L1 expression subgroups"; Non small cell lung cancer (Daiichi Sankyo) - ASCO 2025

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

Datopotamab Deruxtecan for Metastatic Hormone Receptor Positive HER2 Low or Negative Breast Cancer (ASCO 2025) - No abstract available

Metastases • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2

TROPION-Breast04: A Phase III Randomised Study to Evaluate Dato-DXd and Durvalumab for Neoadjuvant/Adjuvant Treatment of Triple-Negative or Hormone Receptor-low/HER2-negative Breast Cancer (clinicaltrials.gov) - P3 | N=1900 | Recruiting | Sponsor: AstraZeneca | Trial completion date: Aug 2030 ➔ Nov 2032 | Trial primary completion date: Mar 2028 ➔ Nov 2028

Trial completion date • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2

Diffuse interstitial lung disease induced by antibody-drug conjugates (PubMed, Rev Mal Respir) - "Among the many ADCs being developed, several can cause ILD of varying grades and intensity. Knowledge of their risks, diagnostic and therapeutic modalities is required in order to quickly detect and treat ADC-induced ILD."

Journal • Review • Interstitial Lung Disease • Lung Cancer • Nephrology • Non Small Cell Lung Cancer • Oncology • Pulmonary Disease • Renal Disease • Respiratory Diseases • Solid Tumor • CEACAM5 • ERBB3 • HER-2 • MET

Efficacy and Safety of Antibody-Drug Conjugates for Lung Cancer Therapy: A Systematic Review of Randomized and Non-Randomized Clinical Trials. (PubMed, Pharmaceutics) - "Five ADCs were evaluated: trastuzumab deruxtecan (T-DXd), trastuzumab emtansine (T-DM1), telisotuzumab vedotin, patritumab deruxtecan, and datopotamab deruxtecan (Dato-DXd)...Dato-DXd demonstrated improved ORR (26.4% vs. 12.8%) and PFS (4.4 vs. 3.7 months) compared to docetaxel...While ADCs offer significant clinical benefits, careful patient selection and proactive management of adverse events remain crucial. Ongoing and future trials will further refine the role of ADCs in personalized NSCLC treatment, potentially expanding their tumor-agnostic use to broader patient populations."

Clinical • IO biomarker • Journal • Review • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • HER-2 • MET • TACSTD2

From Development to Current Status: The Evolution of ADCs (GBCC 2025) - "Since the approval of trastuzumab emtansine for the treatment of HER-2 positive breast cancer in 2013, antibody drug conjugates (ADC’s) have rapidly become the preferred first and second-line agents for patients with metastatic breast cancer across tumor subtypes. We will then discuss seminal trials that led to approval of trastuzumab deruxtecan, sacituzumab govitecan, and most recently, datopotamab deruxtecan. We will discuss drug sequencing across tumor subtypes, and will review on-going efforts to determine optimal sequencing based on tumor subtype and biomarker expression."

Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Development and preclinical characterization of HER2×Trop-2 bispecific antibody-drug conjugates (bsADCs) with auristatin microtubule inhibitors (AACR 2025) - "HER2 is a well-established target for ADCs such as trastuzumab emtansine and trastuzumab deruxtecan, demonstrating significant clinical benefits in HER2-positive breast cancers...Trop-2-directed ADCs such as sacituzumab govitecan and datopotamab deruxtecan have demonstrated potent antitumor efficacy in a broad range of solid tumors including patients with advanced triple-negative breast cancer, lung cancers and urothelial cancers... HER2×Trop2 bsADCs represent a novel and exciting class of therapeutic agents with the potential to transform the treatment of multiple cancer types. Preclinical studies of HER2×Trop2 bsADCs have demonstrated that bsADCs can effectively inhibit tumor growth and prolong survival in xenograft animal models, with a favorable safety profile and low incidence of severe adverse events."

Preclinical • Breast Cancer • Genito-urinary Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Lung Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • Urothelial Cancer • HER-2 • TACSTD2

Decoding Clinical Trials in Metastatic Breast Cancer: Practical Insights for Optimal Therapy Sequencing. (PubMed, Am Soc Clin Oncol Educ Book) - "In addition, for both ER+ and ER- metastatic breast cancer (MBC) with nonoverexpressed human epidermal growth factor receptor 2 (HER2), this review highlights pivotal trials investigating antibody-drug conjugates (ADCs)-including trastuzumab deruxtecan, sacituzumab govitecan, and datopotamab deruxtecan-and the challenges related to control arm selection and crossover that may affect outcome interpretation. Finally, for patients with HER2-positive disease, the review explores first-line and maintenance strategies-including insights from landmark trials like CLEOPATRA and PATINA-and addresses the impact of brain metastases on sequencing decisions. By critically appraising current data and identifying gaps in biomarker-guided and sequencing-specific strategies, this review provides practical insights to inform clinical practice and optimize personalized treatment plans for patients with MBC."

Journal • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • CDK4 • ER • HER-2

DATROWAY plus durvalumab and chemotherapy demonstrate encouraging pathological response rates in patients with early-stage resectable NSCLC (Daiichi Sankyo Press Release) - P2 | N=630 | NeoCOAST-2 (NCT05061550) | Sponsor: AstraZeneca | "Final results from Arm 4 of the NeoCOAST-2 phase 2 platform trial evaluating neoadjuvant DATROWAY plus AstraZeneca’s anti-PD-L1 therapy IMFINZI (durvalumab) and single-agent platinum chemotherapy were presented during a poster session (#8046) on Saturday, May 31 and showed the combination demonstrated a pathologic complete response (pCR) rate of 35.2% (95% CI: 22.7-49.4) and a major pathologic response (mPR) rate of 63% (95% CI: 48.7-75.7). This was numerically higher than response rates shown by other combination regimens evaluated in Arm 1 and Arm 2 of NeoCOAST-2; however, the trial was not powered to make direct statistical comparisons between arms."

P2 data • Non Small Cell Lung Cancer