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

TROPION-Breast05: A Phase III Study of Dato-DXd With or Without Durvalumab Compared With Investigator's Choice of Chemotherapy in Combination With Pembrolizumab in Patients With PD-L1 Positive Locally Recurrent Inoperable or Metastatic Triple-negative Breast Cancer (clinicaltrials.gov) - P3 | N=625 | Recruiting | Sponsor: AstraZeneca | Trial completion date: Apr 2029 ➔ Mar 2031 | Trial primary completion date: Sep 2026 ➔ Dec 2026

Trial completion date • Trial primary completion date • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • PD-L1

TROPION-Breast05: a randomized phase III study of Dato-DXd with or without durvalumab versus chemotherapy plus pembrolizumab in patients with PD-L1-high locally recurrent inoperable or metastatic triple-negative breast cancer. (PubMed, Ther Adv Med Oncol) - P3 | "Patients (⩾18 years) will be randomized 1:1 to receive Dato-DXd (6 mg/kg intravenously (IV) every 3 weeks (Q3W)) plus durvalumab (1120 mg IV Q3W) or investigator's choice of chemotherapy (ICC; paclitaxel, nab-paclitaxel, or gemcitabine plus carboplatin) plus pembrolizumab (200 mg IV Q3W). The findings of this trial could lead to a new treatment option for these patients. ClinicalTrials.gov identifier: NCT06103864 (Date of registration: 27 October 2023)."

Journal • P3 data • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • PD-L1

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) - "The abstract will be released to the public on May 22, 2025 at 4:00 PM CDT"

Retrospective data • Lung 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

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

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) - "The abstract will be released to the public on May 22, 2025 at 4:00 PM CDT"

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

SYS6042, a novel anti-TROP2 pH-sensitive antibody-drug conjugate (ADC) with improved therapeutic window (AACR 2025) - "In clinical, Dato-DXd, Trodelvy and SKB264 showed obvious on-target toxicity or off-target toxicity, which affect clinical development and patient benefit. The highest non-severely toxic dose (HNSTD) for monkeys was defined as 30 mg/kg for repeating dosing. Based on these results, it demonstrates that the novel design of SYS6042 leads to an improved therapeutic window, which would help address unmet needs in the treatments of TROP2-positive tumors."

Oncology • 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

Potent antitumor efficacy of Dato-DXd compared with sacituzumab govitecan in brain metastases mouse model of triple negative breast cancer (AACR 2025) - "In this mouse model of brain metastases, Dato-DXd showed more potent antitumor activity against intracranially transplanted tumors of TNBC with higher accumulation of the payload in tumors compared with SG. The dosing utilized in this model does not directly correlate with human dosages, necessitating caution in interpreting the study results. This study warrants further clinical evaluation of Dato-DXd in TNBC patients with brain metastases."

Preclinical • Brain Cancer • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • TACSTD2

ABN202 (αTROP2), a sacituzumab-interferon-beta mutein fusion protein: a novel approach beyond antibody-drug conjugate therapeutics in ADC-naïve and ADC-refractory cancers (AACR 2025) - "TROP2-targeting antibody-drug conjugates (ADCs) such as Sacituzumab-govitecan (SG) and Datopotamab deruxtecan (Dato-DXd) demonstrated promising clinical efficacy in patients with TROP2-positive cancers. The preclinical toxicity profiles of SG, Dato-DXd, and ABN202 (αTROP2) were evaluated using human immune cells and hIFNAR KI mouse models.In conclusion, ABN202 (αTROP2) demonstrated potent anti-cancer efficacy and a tolerable safety profile compared to SG and Dato-DXd. Our findings suggest that ABN202 (αTROP2) represents a novel therapeutic approach beyond ADCs for both ADC-naïve and ADC-refractory cancers."

Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • IFNAR1 • IFNB1

OBI-992, a novel TROP2 antibody-drug conjugate, exhibits distinct resistance profiles compared to other TROP2 targeting ADCs (AACR 2025) - "As a result, several antibody-drug conjugates (ADC) have been developed targeting TROP2, such as Sacituzumab Govitecan (SG) and Datopotamab Deruxtecan (Dato-Dxd)... OBI-992, a novel TROP2 targeting ADC, emerges as a potential promising therapeutic option for patients who are resistant to other TROP2 targeting ADCs such as SG and Dato-Dxd. OBI-992 exhibits distinct resistance profiles compared to other TROP2 targeting ADCs. Understanding of potential mechanisms of resistance can provide potential combination options for TROP2-targeting ADCs to combat the drug resistance.Keywords: OBI-992, TROP2, antibody-drug conjugate, Colon cancer, resistance"

Colon Cancer • Colorectal Cancer • Oncology • Solid Tumor • ATRX • BRCA2 • MET • PALB2 • TOP1

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

KH815, a novel dual-payload TROP2-directed antibody-drug conjugate, shows potent antitumor efficacy in pre-clinical tumor model (AACR 2025) - "Several antibody-drug conjugates (ADCs) targeting TROP2, such as sacituzumab govitecan and datopotamab deruxtecan, have shown promising anti-tumor activity in multiple solid tumors, particularly in breast cancer. The non-GLP toxicity study in cynomolgus monkeys provided evidence of the favorable safety profile of KH815, the highest non-severely toxic dose (HNSTD) is 40 mg/kg/dose.In summary, KH815, an ADC with dual toxins and unique mechanisms of action, displayed superior anti-tumor effects, the ability to overcome drug resistance, and an acceptable safety profile in preclinical studies. These findings support the potential of KH815 as a promising advanced therapeutic candidate for tumors."

Preclinical • Breast Cancer • Oncology • Solid Tumor

The role of N-terminal cleavage of Trop2 in tumor progression and therapeutic resistance in triple negative breast cancer (AACR 2025) - "High expression of Trop2 has led to the development of antibody-drug conjugates (ADCs) targeting wild-type Trop2, including Sacituzumab govitecan (SG) and Datopotamab deruxtecan (Dato-dxd). Our studies found that N-terminally cleaved Trop2 induces a proliferative phenotype in vivo, reduce binding capacity of Trop2 ADCs, and are more resistance to ADC-induced killing in vitro. These data provide insight into the potential importance of N-terminally cleaved Trop2 in tumor progression and drug resistance that have not been explored. Future experiments will elucidate the mechanisms that underlie cleavage of Trop2 and refining Trop2-targeting therapies."

Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ADAM10 • HER-2 • TACSTD2

The development of PDX models from ADC-resistant breast cancer patient tissue for next-generation therapy evaluation (AACR 2025) - "Trop-2 targeting ADCs like sacituzumab govitecan (SG), datopotamab deruxtecan (Dato-DXd), and SKB-264 have shown success in clinical settings. In this study, the limited response of the models despite HRD may suggest other factors affecting the drug's efficacy targeting DNA repair mechanism, such as acquired resistance mechanisms or drug efflux activity, overriding the vulnerability provided by HRD.Conclusion The study successfully established longitudinal breast cancer PDX models from a patient with demonstrated resistance to Trop2-ADCs. These models will aid in evaluating new treatments or combination therapies and understanding drug resistance mechanisms."

Clinical • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HRD • TACSTD2

KH815, a novel dual-payload TROP2-directed antibody-drug conjugate, shows potent antitumor efficacy in pre-clinical tumor model [WITHDRAWN] (AACR 2025) - "Several antibody-drug conjugates (ADCs) targeting TROP2, such as sacituzumab govitecan and datopotamab deruxtecan, have shown promising anti-tumor activity in multiple solid tumors, particularly in breast cancer. The non-GLP toxicity study in cynomolgus monkeys provided evidence of the favorable safety profile of KH815, the highest non-severely toxic dose (HNSTD) is 40 mg/kg/dose.In summary, KH815, an ADC with dual toxins and unique mechanisms of action, displayed superior anti-tumor effects, the ability to overcome drug resistance, and an acceptable safety profile in preclinical studies. These findings support the potential of KH815 as a promising advanced therapeutic candidate for tumors."

Preclinical • Breast Cancer • Oncology • Solid Tumor

DATO-Base: A phase II study of DATOpotamab deruxtecan for patients with breast cancer brain metastases or leptomeningeal disease. (ASCO 2025) - P2 | "Clinical Trial Registration Number: NCT06176261 The abstract will be released to the public on May 22, 2025 at 4:00 PM CDT"

Clinical • P2 data • Breast Cancer • Oncology • Solid Tumor

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 | "Clinical Trial Registration Number: NCT06350097 The abstract will be released to the public on May 22, 2025 at 4:00 PM CDT"

Clinical • Metastases • P3 data • Lung 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 | "Clinical Trial Registration Number: NCT04612751 The abstract will be released to the public on May 22, 2025 at 4:00 PM CDT"

Clinical • Metastases • 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 | "Clinical Trial Registration Number: NCT04526691 The abstract will be released to the public on May 22, 2025 at 4:00 PM CDT"

Clinical • Metastases • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

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

DIAMOND: Investigating Datopotamab Deruxtecan Plus Durvalumab Versus Datopotamab Deruxtecan in Patients With PDL1-negative Metastatic Triple-negative Breast Cancer (clinicaltrials.gov) - P2 | N=140 | Not yet recruiting | Sponsor: Queen Mary University of London

New P2 trial • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

Screening or Early Detection of Brain Metastases and the Treatment in the Era of New Agents (GBCC 2025) - "Advances in systemic therapy have been greatest in HER2-positive breast cancer, where the current NCCN guidelines include a growing list of CNS-active regimens, such as tucatinib-capecitabine-trastuzumab, T-DXd, T-DM1, high dose trastuzumab and pertuzumab, neratinib-capecitabine, and lapatinib-capecitabine...There are a number of novel blood-brain-barrier (BBB) penetrant HER2-targeted tyrosine kinase inhibitors (e.g. ZN1041, IAM1363) in early-phase clinical trials. For patients with HER2-negative tumors, the data are more sparse; however, activity of chemotherapy drugs such as capecitabine, anthracyclines, platinums, and eribulin has been reported...Ongoing clinical trials are testing a wide variety of ADCs, such as patritumab deruxtecan, datopotamab deruxtecan, ARX788, and others...For example, the ELECTRA trial is testing the combination of elacestrant and abemaciclib. Overall, the expanding array of systemic options with clinically meaningful intracranial activity, as..."

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 • ER • HER-2

Therapeutic Potential of Datopotamab Deruxtecan in the Treatment of Advanced Non-Small Cell Lung Cancer: Evidence to Date. (PubMed, Onco Targets Ther) - "Dato-DXd used along with pembrolizumab, with or without systemic chemotherapy, in TROPION Lung 02 with promising efficacy results. Dato-DXd is currently pending approval from the US Food and Drug Administration (FDA). If approved, datopotamab deruxtecan will be the first TROP2-directed antibody-drug conjugate for non-small cell lung cancer."

IO biomarker • Journal • Review • Alopecia • Dental Disorders • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Stomatitis

OBI-902, a novel TROP2 targeted antibody-drug conjugate via GlycOBI® platform, has favorable pharmacokinetics and sustained antitumor activities in challenging solid tumors (AACR 2025) - "The antitumor activity studies of OBI-902 were conducted in NSCLC, PC, GC, and challenging CRC xenograft mouse models with Dato-DXd, SG, or MK-2870 as benchmarks. Similarly, in the large-tumor PC xenograft model, OBI-902 prolonged survival beyond day 50, while all mice in the benchmark groups were sacrificed by day 28. OBI-902 can efficiently deliver payload to the site of action (tumor) to achieve desirable drug exposure and sustainable antitumor activities in various challenging solid tumors, pointing to its potential to be the best-in-class TROP2 ADC."

PK/PD data • Colorectal Cancer • Gastric Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • TACSTD2 • TOP1