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

Expert consensus on the clinical application of TROP2-targeted antibody-drug conjugates in non-small cell lung cancer (2026 edition) (PubMed, Zhonghua Zhong Liu Za Zhi) - "Trophoblast cell surface antigen 2 (TROP2) has emerged as a pivotal therapeutic target, and TROP2-directed ADCs, including Sacituzumab Tirumotecan, Datopotamab Deruxtecan, and Sacituzumab Govitecan have shown substantial antitumor activity and survival benefits in clinical studies. To further standardize the clinical use and safety management of TROP2 ADCs, this expert consensus systematically reviews current evidence regarding their efficacy and safety in NSCLC. Particular emphasis is placed on strategies for the prevention and management of treatment-related adverse events such as mucositis, myelosuppression, and gastrointestinal toxicities, aiming to provide guidance for the rational and safe application of TROP2 ADCs in NSCLC."

Journal • Review • Lung Cancer • Mucositis • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Developing ADC-resistant tumor models for efficacy evaluation of next-generation anticancer therapies (AACR 2026) - "Trastuzumab deruxtecan (DS8201) targets HER2, and datopotamab deruxtecan (DS1062) targets TROP2. We developed a panel of ADC-resistant tumor models to study mechanisms of acquired resistance. These models provide a valuable preclinical platform for advancing ADC therapy."

ADC • Preclinical • Oncology • ABCB1 • ABCG2

Combination activity of T-DXd and dato-DXd with DNA damage response inhibitors (ESMO-TAT 2026) - "We profiled the activity of two TOP1i-charged ADCs (T-DXd, Dato-DXd), in combination with DDRi, targeted against ATM (AZD1390), ATR (ceralasertib), PARP (olaparib, saruparib) or WEE1 (adavosertib), using preclinical cancer models. Combinations of TOP1i-ADCs with selected DDR inhibitors and optimized dosing schedules, enhance therapeutic response and reduce toxicity, guiding ongoing and future clinical investigations."

Oncology • PARP1 • TOP1

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

Profiling membrane antigen expression of select antibody-drug conjugate (ADC) targets in EGFR-altered non-small cell lung cancer treated with osimertinib (AACR 2026) - "In patients with EGFR-altered NSCLC, we identified high expression of ERBB2, MET, and TACSTD2 (TROP2) in both pre- and post-treated samples. This may provide rationale for use of these ADC targets in second-line therapy, such as seen in recent approvals for trastuzumab deruxtecan in ERBB2-mutated, telisotuzumab vedotin in c-MET over-expressing, and datopotamab deruxtecan in EGFR-altered NSCLC. Notably, high MET pre-treatment expression was associated with poor survival outcome and appeared to be associated with post-osimertinib resistance."

ADC • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • ERBB3 • HER-2 • MET • NECTIN4 • TACSTD2

How case based education elevated clinical performance in metastatic breast cancer management: A study for TROP2 directed antibody drug conjugates (AACR 2026) - "Background: The treatment landscape of metastatic breast cancer (mBC) has advanced with antibody-drug conjugates (ADCs), notably the TROP2-directed agents sacituzumab govitecan and datopotamab deruxtecan. This case-based CME activity effectively improved clinician K/C regarding TROP2-directed ADCs for HER2- mBC and supported sustained practice change. Personalized, digital education formats may accelerate integration of newly available and emerging therapies into oncology care."

ADC • Clinical • Metastases • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Safety profile of post-CDK4/6 treatments in HR+/HER2− metastatic breast cancer (mBC): A network meta-analysis (AACR 2026) - "Among ET-based strategies, the lowest RRs were observed for: imlunestrant alone (0.98, 95% CI 0.92-1.05) for any G AEs; camizestrant 75 mg (0.81, 0.36-1.83) for G≥3 AEs; elacestrant (1.45, 0.66-3.16) for AEs leading to discontinuation. While among antibody-drug conjugates (ADCs) the lowest RRs were observed for: sacituzumab govitecan (SG) for any G AEs (1.00, 0.99-1.01); datopotamab deruxtecan (Dato-DXd) (0.47, 0.37-0.59) for G≥3 AEs; SG (0.83, 0.26-2.66) for AEs leading to discontinuation...Among ET-based options, novel mono-ETs (oral SERDs and PROTACs) showed the lowest risk of discontinuation and G≥3 AEs. Among ADCs, TROP2-directed agents had fewer discontinuations, while ADCs with DXd as a payload showed higher rates of any G AEs but (except for DESTINY-Breast06) lower G≥3 AEs risk than other tx strategies."

Metastases • Retrospective data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

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

A novel synergistic dual-payload TROP2 ADC (CTPH-03) delivering enhanced safety by increased MTD (AACR 2026) - "Although there are two FDA-approved ADCs, Trodelvy and Datroway, anti-tumor efficacy from these TROP2 ADCs have been subpar due to dose-limiting toxicities. We have developed a novel TROP2-targeting dual-payload ADC (AD2C) by using MMAE-based dual-payload combination to address this unmet need. The presentation highlights advantages of the synergistic dual-payload TROP2 ADC over known single-payload ADCs or other dual-payload ADC formats by demonstrating, (1) in vitro cytotoxicity for cancer cells having different TROP2 expression levels (2) in vivo efficacy in various CDX(cancer-cell derived xenograft) models (3) in vivo ADC stability in rats and monkeys by PK(pharmacokinetics) studies, and (4) preliminary toxicity studies conducted in mice and monkeys.In due course, we are currently in preparation of PDX efficacy studies for further confirming its in vivo efficacy over various patient-derived tumor cells, and IND-enabling toxicology studies in order to quickly move..."

ADC • Clinical • Oncology • TACSTD2

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

Datopotamab Deruxtecan Plus Pembrolizumab With or Without Platinum-Based Chemotherapy for Advanced or Metastatic NSCLC: The Phase Ib TROPION-Lung02 Trial. (PubMed, J Thorac Oncol) - P1 | "Dato-DXd plus pembrolizumab therapy (with and without Pt-CT) exhibited appreciable safety and durable antitumor activity across PD-L1 expression levels in patients with amNSCLC."

IO biomarker • Journal • P1 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PD-L1 • TACSTD2

Real-world data of datopotamab deruxtecan in an expanded access program for pretreated metastatic non-small cell lung cancer: The Dato real-ICO study (ELCC 2026) - "In the phase III TROPION-Lung01 trial, datopotamab deruxtecan (Dato-DXd) improved progression-free survival (PFS) versus docetaxel, mainly in nonsquamous disease. Interstitial lung disease/pneumonitis occurred in 2 patients (5.3%, both grade ≥3). Non grade 5 AE were observed.Conclusions Patients treated with Dato-DXd in the EAP showed similar PFS to that of TROPION-Lung01 trial patients, with manageable toxicity."

Clinical • IO biomarker • Metastases • Real-world • Real-world evidence • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • PD-L1

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) - "Importantly, data also indicated the potential of osimertinib pre-treatment to enhance TROP2 expression and Dato-DXd internalization in EGFRm models.Conclusions These preclinical data support the notable clinical activity of Dato-DXd in EGFRm NSCLC and provide a potential mechanistic rationale for why EGFRm disease has broad inherent sensitivity to Dato-DXd. Further validation in clinical cohorts is warranted."

Preclinical • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ABCC1 • EGFR • TACSTD2

Plinabulin boosts antitumor efficacy of topoisomerase inhibitor-based antibody-drug conjugates without or with immune checkpoint inhibitor (AACR 2026) - "Preclinically, Plin boosts irinotecan activity in human colon cancer models and reduces topotecan-induced neutropenia. Here we investigated Plin synergy with TOP1-ADC in-vitro, and with or without PD-1/L1 inhibitor pembrolizumab (Pembro) or atezolizumab (Atezo) in-vivo. For combinations in-vitro, HER2+ KPL-4 breast cancer cells were treated with Plin (1.46 - 46.8 nM), T-DXd (0.105 - 3.37 μM) or both. For combinations in-vivo, MC38 mouse colon adenocarcinoma cells overexpressing hTROP2 (hTROP2-MC38) or hHER2 (hHER2-MC38), were inoculated in B-hPD-1 or B-hPD-1/hPD-L1/hHER2 mice respectively, and antitumor activities of Plin (7.5 mg/kg) plus Dato-DXd (5 mg/kg) ± Pembro (0.3 mg/kg) or T-DXd (3 mg/kg) ± Atezo (8 mg/kg) were evaluated. On HER2+ KPL-4 cells, Plin showed synergistic activity with T-DXd with median CI <1 at 1:1, 2:1 and 4:1 ratios (T-DXd:Plin)... Plinabulin is a Phase 3 novel agent clinically validated to promote DC maturation and T-cell activation,..."

ADC • Checkpoint inhibition • Clinical • Breast Cancer • Colon Adenocarcinoma • Colon Cancer • Colorectal Adenocarcinoma • Colorectal Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2 • PD-L1 • TACSTD2 • TOP1

Alopecia in cancer immunotherapy: Incidence and patterns with monoclonal antibodies and antibody-drug conjugates (AACR 2026) - "Antibody-drug conjugates (ADCs), including datopotamab deruxtecan, trastuzumab deruxtecan, tisotumab vedotin, enfortumab vedotin, and disitamab vedotin, showed the highest rates of alopecia, ranging from 37% to 56% (predominantly grade 1-2)...In contrast, immune checkpoint inhibitors such as cemiplimab (anti-PD-1) and trastuzumab (anti-HER2) were rarely associated with alopecia (1-2.2% incidence, grade 1-2) in lung and breast cancer patients, respectively...In contrast, antibody-only and interferon therapies demonstrated substantially lower rates (1-28%). Recognizing these trends across biologic classes can help clinicians set patient expectations, guide counseling, and implement supportive measures for those experiencing hair loss throughout treatment."

ADC • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • IFNAR2 • TOP1

What can we expect from a combination of datopotamab deruxtecan, carboplatin, and pembrolizumab for brain metastases from non-small cell lung cancer? (PubMed, Expert Opin Emerg Drugs) - No abstract available

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

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

TROP2 normalised membrane ratio (NMR) assessed by quantitative continuous scoring (QCS): Association with clinical outcomes with datopotamab deruxtecan (Dato-DXd) ± osimertinib (osi) in EGFR-mutated (EGFRm) NSCLC (ELCC 2026) - P1, P2, P3 | "Data indicate that pts with EGFRm NSCLC derive benefit from Dato-DXd irrespective of TROP2 NMR status, suggesting limited value in pt selection for Dato-DXd therapy in this setting. Benefit of Dato-DXd in pts with EGFRm NSCLC is being tested in phase III studies (1st-line osi + Dato-DXd, TROPION-Lung14, NCT06350097; 2nd-line Dato-DXd ± osi, TROPION-Lung15; NCT06417814)."

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

Antitumor activity of datopotamab deruxtecan in a co-clinical trial with patient derived xenografts (AACR 2026) - "A pretreatment PDX model was generated from a patient with PDAC who had received topoisomerase inhibitor treatment (FOLFIRINOX) as well as gemcitabine/abraxane, and had PD as best response to Dato-DXd...Combinations may further enhance antitumor activity. Further studies are needed to explore the mechanisms of resistance and potential combinations."

Clinical • Breast Cancer • Esophageal Adenocarcinoma • Esophageal Cancer • Head and Neck Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor • Urothelial Cancer • HER-2 • TACSTD2

Functional organoid screening uncovers target dependency and bystander killing in TROP2 ADCs (AACR 2026) - "The combined organoid screening and HCI workflow provides a robust, translationally relevant platform for ADC evaluation, integrating efficacy profiling, mechanistic validation, and functional bystander effect modeling. CRISPR-generated isogenic organoids enable precise dissection of target dependency and resistance, supporting the preclinical optimization of TROP2-targeted ADCs."

ADC • Oncology • TACSTD2

Dual-payload antibody drug conjugate targeting TROP2: Multi-Payload Conjugates™ targeting orthogonal mechanisms of cell killing (AACR 2026) - "Sacituzumab govitecan (SG), is approved as a 3rd line therapy in metastatic HER2 negative breast cancer...In head-to-head comparisons, CATB-101 outperforms T-DXd, SG and Dato-DXd with full tumor elimination at low doses... Advances have been made in the design of ADCs to expand to previously unaddressed populations. High patient relapse and the failure of recent mono-payload ADCs in late-stage trials indicate a need for next generation multi-payload conjugates. Catena's MPCs™ offer a next step in ADC design and allow for targeted delivery of multiple mechanisms of action with a single MPC™ while reducing off-target toxicity."

ADC • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • EGFR • HER-2 • TACSTD2 • TOP1

TROPION-Lung17: Phase III Study of Datopotamab Deruxtecan Versus Docetaxel in Previously Treated TROP2-positive Advanced or Metastatic Non-squamous NSCLC Without Actionable Genomic Alterations (clinicaltrials.gov) - P3 | N=400 | Recruiting | Sponsor: AstraZeneca | N=103 ➔ 400

Enrollment change • Trial initiation date • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • BRAF • HER-2 • KRAS • RET • ROS1

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

WEE1 inhibition as a therapeutic strategy in triple-negative breast cancer: Evaluating single agent and combination activity of azenosertib in preclinical models (AACR 2026) - "We demonstrated in vitro and in vivo evidence that TNBC models are susceptible to WEE1 inhibition. Our findings suggest that azenosertib as a single agent, or in combination with standard-of-care therapies, may be a potential treatment strategy for TNBC and warrants further exploration."

IO biomarker • Preclinical • Breast Cancer • Oncology • Ovarian Cancer • Solid Tumor • Triple Negative Breast Cancer • CCNE1

SHEDDING LIGHT ON PATIENT-REPORTED OUTCOME MEASURE UTILIZATION ACROSS NSCLC THERAPIES (ISPOR 2026) - "Within monotherapies, disease-specific quality-of-life (QOL) measures, particularly EORTC QLQ-C30 (n=11) and EORTC QLQ-LC13 (n=8), were frequently used in trials of ALK inhibitors (e.g., alectinib), PD-L1 inhibitors (e.g., atezolizumab, durvalumab), and PD-1 inhibitors (e.g., nivolumab, and pembrolizumab). Tyrosine kinase inhibitors (e.g., zongertinib, entrectinib) combined disease-specific EORTC QLQ-C30 and generic QOL instruments, such as EQ-5D (n= 4). In contrast, TIGIT inhibitors (e.g. rilvegostomig) and antibody-drug conjugates (e.g. dato-DXd) predominantly utilize PROMIS, which assesses general health and physical and mental functioning rather than QOL (n= 4). PRO measures remain underutilized in NSCLC monotherapy trials and are primarily positioned as supportive endpoints. PRO measures remain underutilized in NSCLC monotherapy trials and are primarily positioned as supportive endpoints. Substantial heterogeneity in PRO instrument selection suggests a lack of..."

Clinical • Patient reported outcomes • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • TIGIT