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

Clinical trial data presentation, Datopotamab deruxtecan (Dato-DXd) vs chemotherapy (CT) in previously-treated inoperable or metastatic hormone receptor-positive, HER2-negative (HR+/HER2–) breast cancer (BC): Final overall survival (OS) from the phase III TROPION-Breast01 trial (ESMO Plenary Feb 2025) - P3 | "Clinical trial identification NCT05104866"

Clinical • Metastases • P3 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • 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 (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 Ib/II BEGONIA study (ESMO 2025) - P1/2 | "Conclusions In 1L a/mTNBC, the combination of Dato-DXd + D continued to demonstrate robust antitumour activity across both arms. The safety profile was manageable with no new safety signals."

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

First-line (1L) datopotamab deruxtecan (Dato-DXd) vs chemotherapy in patients with locally recurrent inoperable or metastatic triple-negative breast cancer (mTNBC) for whom immunotherapy was not an option: Primary results from the randomised, phase III TROPION-Breast02 trial (ESMO 2025) - P1, P3 | "Methods Adult pts with previously untreated locally recurrent inoperable or mTNBC, for whom immunotherapy was not an option, were randomised 1:1 to Dato-DXd (6 mg/kg IV Q3W) or investigator's choice of chemotherapy (ICC; [nab]-paclitaxel/ capecitabine/ eribulin mesylate/ carboplatin). The Dato-DXd safety profile was manageable. Results support Dato-DXd as the new 1L standard of care."

Clinical • Late-breaking abstract • Metastases • P3 data • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • PD-L1

Intracranial activity of datopotamab deruxtecan (Dato-DXd) for patients with HER2-negative breast cancer and leptomeningeal disease (LMD): Results from Cohort C of the DATO-BASE phase 2 trial (SABCS 2025) - P2 | "Patients had a median of 2.5 (range 0-6) prior lines of cytotoxic treatment, with 7 who had received prior ADCs (3 T-DXd, 2 SG, 2 both ADCs). In this exploratory cohort of DATO-BASE, Dato-DXd demonstrated promising intracranial activity in patients with HER2-negative MBC and LMD, including radiographic responses and improvement in neurological symptoms in most patients with baseline deficits. Outcomes appeared more favorable in ADC-naïve patients, although numbers were limited."

Clinical • P2 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2 • TACSTD2

Antibody-Based Therapeutics in Breast Cancer: Clinical and Translational Perspectives. (PubMed, Antibodies (Basel)) - "Monoclonal antibodies such as trastuzumab and pertuzumab have established HER2-targeted therapy as a standard of care, while immune checkpoint inhibitors have introduced immunotherapy into the treatment of triple-negative breast cancer. The emergence of antibody-drug conjugates (ADCs), including trastuzumab deruxtecan, sacituzumab govitecan, and datopotamab deruxtecan, has further expanded the available therapeutic options...This review summarizes the biological rationale, clinical evidence, resistance mechanisms, and safety profiles of therapies based on monoclonal antibodies, bispecific antibodies, and antibody-drug conjugates in breast cancer. The development of these treatment modalities fosters the implementation of personalized, immunologically informed treatment strategies that are redefining precision oncology in breast cancer."

Journal • Review • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor 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 H2 2026 (Daiichi Sankyo) - Q3 FY2026 Results

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

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

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

Payload Diversification Overcomes Resistance and Guides Sequential Antibody-Drug Conjugate Therapy in Breast Cancer. (PubMed, Clin Cancer Res) - "Cross-resistance to sequential ADCs is primarily driven by shared payload mechanisms rather than loss of the target. Our data also suggest that the clinical benefit of sequential Topo1-based ADCs may be reduced following disease progression on a Topo1-based ADC, likely due to these shared resistance pathways. Importantly, switching to ADCs with non-cross-resistant payload classes may offer a more effective approach to guide ADC sequencing in patients with metastatic breast cancer, supporting payload diversification as a clinically actionable strategy."

Journal • Breast Cancer • Oncology • Solid Tumor

Product Performance (Investing.com) - "ENHERTU continues to be a key growth driver, maintaining the number one new patient share across major countries and regions. The product generated global sales of JPY 506.8 billion in Q3 YTD, representing a 25.3% year-over-year increase and achieving 73.0% progress against the October forecast....DATROWAY, another important product in Daiichi Sankyo’s oncology portfolio, has exceeded initial forecasts in both the US and Japan, primarily driven by lung cancer indications. The company has treated more than 3,000 patients globally since launch, with the treatment rate approximately 1.5 times that of the prior quarter."

Commercial • Sales • Biliary Tract Cancer • Bladder Cancer • Cervical Cancer • Colorectal Cancer • Endometrial Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Non Small Cell Lung Cancer • Ovarian Cancer • Pancreatic Cancer • Thoracic Cancer • Urothelial Cancer • Uterine Cancer

TROPION-Breast04: a randomized phase III study of neoadjuvant datopotamab deruxtecan (Dato-DXd) plus durvalumab followed by adjuvant durvalumab versus standard of care in patients with treatment-naïve early-stage triple negative or HR-low/HER2- breast cancer. (PubMed, Ther Adv Med Oncol) - P3 | "Approximately 1728 patients (aged ⩾18 years) will be randomized 1:1 to eight cycles of neoadjuvant Dato-DXd (6 mg/kg intravenously (IV) every 3 weeks (Q3W)) plus durvalumab (1120 mg IV Q3W) followed by nine cycles of adjuvant durvalumab (1120 mg IV Q3W) with or without chemotherapy versus eight cycles of pembrolizumab (200 mg IV Q3W) plus chemotherapy followed by nine cycles of adjuvant pembrolizumab (200 mg IV Q3W) with or without chemotherapy. The findings of this trial could lead to promising treatment options for these patients. ClinicalTrials.gov identifier: NCT06112379."

Journal • P3 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2

Resistance Mechanisms and Post-Trastuzumab Deruxtecan (T-DXd) Strategies in HER2+ and HER2-Low Breast Cancer: From Biology to Clinical Practice. (PubMed, Crit Rev Oncol Hematol) - "Novel agents such as ARX788, patritumab deruxtecan, and Dato-DXd demonstrate promise in overcoming resistance through diversified mechanisms. Real-world data further support a "three-step strategy" involving ADC rechallenge after interim non-ADC therapies, offering a practical, mechanism-informed treatment model. This review provides a framework for precision-guided care in patients with advanced breast cancer and supports ongoing efforts to extend the therapeutic window beyond initial T-DXd benefit."

IO biomarker • Journal • Review • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Datroway + Keytruda: Topline results from P3 TROPION-Lung07 trial (NCT05555732) for 1L advanced or metastatic NSCLC in FY2026 (Daiichi Sankyo) - Q3 FY2025 Results

P3 data: top line • Lung Cancer • Non Small Cell Lung Cancer • Oncology

TROPION-Urothelial03: A phase 2/3 study of datopotamab deruxtecan (Dato-DXd) + platinum chemotherapy (CT) vs gemcitabine + platinum CT in participants with locally advanced or metastatic urothelial carcinoma (la/mUC) with progression on or after enfortumab vedotin (EV) + pembrolizumab (pembro). (ASCO-GU 2026) - P2/3 | "Clinical Trial Registry Number: NCT07129993. The full, final text of this abstract will be available on Feb 23 at 05:00 PM EST."

Metastases • P2/3 data • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer

Quarterly Performance Highlights (Investing.com) - "The company reported consolidated revenue of JPY 1,533.5 billion, representing a 12.1% year-over-year increase, while core operating profit grew 8.8% to JPY 249.2 billion....The revenue growth was primarily driven by the oncology business unit, which saw a remarkable 102.1% year-over-year increase. ENHERTU and DATROWAY were the standout performers, contributing JPY 85.5 billion and JPY 22.5 billion respectively to the revenue increase."

Commercial • Biliary Tract Cancer • Bladder Cancer • Cervical Cancer • Colorectal Cancer • Endometrial Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Non Small Cell Lung Cancer • Ovarian Cancer • Pancreatic Cancer • Thoracic Cancer • Urothelial Cancer • Uterine Cancer

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

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

AstraZeneca and Daiichi Sankyo’s supplemental Biologics License Application (sBLA) for Datroway (datopotamab deruxtecan) has been accepted and granted Priority Review in the US for the treatment of adult patients with unresectable or metastatic triple-negative breast cancer (TNBC) who are not candidates for PD-1/PD-L1 inhibitor therapy (AstraZeneca Press Release) - "The Prescription Drug User Fee Act date, the FDA action date for its regulatory decision, is anticipated during the second quarter of 2026. The sBLA is being reviewed under Project Orbis....The sBLA is based on results from the TROPION-Breast02 Phase III trial..."

FDA approval • FDA filing • Priority review • Project Orbis • Triple Negative Breast Cancer

Datopotamab deruxtecan (Dato-DXd) + rilvegostomig (rilve) in patients (pts) with locally advanced or metastatic urothelial cancer (a/mUC): Results from the phase II TROPION-PanTumor03 study (ESMO 2025) - P2 | "We present results from pts with a/mUC who received Dato-DXd + rilve, an Fc reduced anti–PD-1/TIGIT bispecific antibody (anti–TIGIT component derived from COM902 [Compugen]). Methods Pts with histologically documented unresectable a/mUC were enrolled in two eligible populations: 1L population, no prior systemic therapy in the a/mUC setting (progression >12 months after platinum-based neoadjuvant or adjuvant therapy permitted), and ineligible for cisplatin-based chemotherapy (CT); 2L population, had received previous platinum-based CT in the a/mUC setting or progressed <12 months after platinum-based neoadjuvant or adjuvant therapy...Conclusions Dato-DXd in combination with rilve showed encouraging efficacy and a manageable safety profile in pts with a/mUC. Table: 3072MO Incidence of AEs, n (%) Dato-DXd + rilve 1L (n=22) 2L (n=18) TRAEs 21 (95.5) 17 (94.4) Grade ≥3 TRAEs 4 (18.2) 7 (38.9) Any TRAE leading to: Dose reduction of any study treatment 12 (54.5) 4..."

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

LIBRA: A Study of Novel Combinations in Non-Small Cell Lung Cancer (NSCLC) (clinicaltrials.gov) - P2 | N=278 | Recruiting | Sponsor: AstraZeneca | Trial primary completion date: Mar 2027 ➔ Apr 2029

Trial primary completion date • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EGFR • PD-L1

A Study of Dato-DXd Versus Investigator's Choice Chemotherapy in Patients With Locally Recurrent Inoperable or Metastatic Triple-negative Breast Cancer, Who Are Not Candidates for PD-1/PD-L1 Inhibitor Therapy (TROPION-Breast02) (clinicaltrials.gov) - P3 | N=644 | Active, not recruiting | Sponsor: AstraZeneca | Trial completion date: Dec 2025 ➔ Nov 2028

Trial completion date • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2 • PGR

A Phase-3, Open-Label, Randomized Study of Dato-DXd Versus Investigator's Choice of Chemotherapy (ICC) in Participants With Inoperable or Metastatic HR-Positive, HER2-Negative Breast Cancer Who Have Been Treated With One or Two Prior Lines of Systemic Chemotherapy (TROPION-Breast01) (clinicaltrials.gov) - P3 | N=732 | Active, not recruiting | Sponsor: AstraZeneca | Trial completion date: Dec 2025 ➔ Jul 2026

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

Identification of DXd sensitivity biomarkers and osimertinib induced datopotamab deruxtecan (Dato-DXd) internalization as potential mechanisms for enhanced activity of Dato-DXd in preclinical models of EGFR-mutant (EGFRm) non-small cell lung cancer (NSCLC) (ELCC 2026) - No abstract available

Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

TROPION-Lung17: A randomised phase 3 study of datopotamab deruxtecan (Dato-DXd) vs docetaxel in patients with previously-treated TROP2 NMR positive advanced/metastatic non-squamous non-small cell lung cancer (NSCLC) without actionable genomic alterations (AGA) (ELCC 2026) - No abstract available

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