Kadcyla (ado-trastuzumab emtansine) / Roche, AbbVie - LARVOL DELTA

Treatment Landscape for HER2-Positive MBC: Exploring Novel Therapies Beyond T-Dxd (GBCC 2025) - "The combination of trastuzumab, pertuzumab, and docetaxel further enhanced survival outcomes and has since become the standard first-line treatment for HER2-positive MBC until present...Trastuzumab emtansine (T-DM1), an antibody-drug conjugate (ADC), has demonstrated improved progression-free survival (PFS) compared to the combination of capecitabine and lapatinib (HER2 targeting tyrosine kinase inhibitor) in the second-line setting...Anti-HER2 biparatopic antibody such as zanidatamab is currently being investigated in phase 3 trial, which enrolls patients who showed disease progression after T-Dxd. Novel ADCs, TKIs are also in development, and combination with immune- checkpoint inhibitor is also being investigated. Major progress is anticipated in the era of HER2 positive MBC, with improvement of survival outcome in near future."

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

A phase 2 basket trial of ado-trastuzumab emtansine for patients with HER2 amplified cancers. (ASCO 2025) - P2 | "Clinical Trial Registration Number: NCT02675829 The abstract will be released to the public on May 22, 2025 at 5:00 PM EDT"

Clinical • P2 data • Pan tumor • Oncology • HER-2

Genomic alterations (GAs) associated with durability of benefit from trastuzumab deruxtecan (T-DXd), trastuzumab emtansine (T-DM1) and sacituzumab govitecan (SG) in metastatic breast cancer (MBC). (ASCO 2025) - "The abstract will be released to the public on May 22, 2025 at 5:00 PM EDT"

Metastases • Breast Cancer • Oncology • Solid Tumor

A phase 2 clinical trial of adjuvant ado-trastuzumab emtansine (T-DM1) for patients with HER2-positive salivary gland cancer. (ASCO 2025) - P2 | "Clinical Trial Registration Number: NCT04620187 The abstract will be released to the public on May 22, 2025 at 5:00 PM EDT"

Clinical • P2 data • Oncology • Salivary Gland Cancer • HER-2

Kadcyla + Tecentriq: Regulatory submissions in US/EU for HER-2+ high-risk early breast cancer in 2027 (Roche) - Q1 2025 Results

EMA filing • FDA filing • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology

Transcriptomic analysis of breast cancer cell lines based on HER2 targeted antibody-drug conjugate responses (GBCC 2025) - "Cytotoxicity assays with trastuzumab emtansine (T-DM1) and T-Dxd revealed strong correlations in the high- expression group. The identification of additional biomarkers is essential for developing precise treatment strategies and predicting therapeutic responses. This study is expected to serve as a foundation for discovering novel biomarkers and improving predictors of treatment efficacy."

Omic analysis • Preclinical • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Real-World Outcomes for HER2-Positive MBC: Exploring Global Perspectives and Regional Differences in Treatment Approaches (GBCC 2025) - "Real-World Data on Recently Approved Agents and HER2-Targeting Biosimilars Recent clinical trials have introduced several promising treatment options for HER2-positive MBC, including T-DXd, tucatinib, and T-DM1. Beyond their clinical trial efficacy, real-world studies support their effectiveness and tolerability in broader patient populations. Additionally, HER2-targeting biosimilars (e.g., Ontruzant, Herzuma) have gained widespread acceptance globally, and real-world evidence supports their comparable efficacy and safety in managing HER2-positive breast cancer."

Clinical • Real-world • Real-world evidence • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Negative Breast Cancer • Oncology • Solid Tumor • ER • HER-2

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

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

Comparative Analysis of Clinical Efficacy and Safety of Pyrotinib Plus Capecitabine versus Trastuzumab Emtansine (T-DM1) as Second-Line Treatment for HER2-Positive Advanced Breast Cancer: A Retrospective Study. (PubMed, Drug Des Devel Ther) - "Neither group recorded any adverse event-related deaths. Pyrotinib plus capecitabine significantly improves median PFS compared to T-DM1 in patients with HER2-positive advanced breast cancer, demonstrating a favorable efficacy profile alongside manageable safety concerns."

Clinical • Journal • Retrospective data • Breast Cancer • Hematological Disorders • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • Thrombocytopenia • HER-2

Breast53: Adjuvant Chemoradiation and Biomarkers of Response in High-risk Breast Cancer (clinicaltrials.gov) - P2/3 | N=45 | Recruiting | Sponsor: University of Virginia | Trial completion date: Oct 2026 ➔ Dec 2029 | Trial primary completion date: Dec 2024 ➔ Dec 2028

Trial completion date • Trial primary completion date • Breast Cancer • Oncology • Solid Tumor

CompassHER2-pCR: Decreasing Chemotherapy for Breast Cancer Patients After Pre-surgery Chemo and Targeted Therapy (clinicaltrials.gov) - P2 | N=2175 | Active, not recruiting | Sponsor: ECOG-ACRIN Cancer Research Group | Recruiting ➔ Active, not recruiting

Enrollment closed • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • Thyroid Gland Carcinoma • Thyroid Gland Follicular Carcinoma • ER • PGR

The impact of ethnicity on benefit from novel drugs approved for breast cancer treatment: a systematic review and meta-analysis of randomized phase 3 trials of the last decade. (SABCS 2024) - "23 phase III RCTs were identified in the aBC setting, with 1547 (11.1%) patients of Asian ethnicity. Experimental drugs tested included CDK4/6i (palbociclib, ribociclib, abemaciclib), SERD (elacestrant), PI3Ki (alpelisib), PARPi (olaparib, talazoparib), broad variety of anti-HER2 drugs (tucatinib, trastuzumab deruxtecan, pertuzumab, T-DM1, neratinib, margetuximab), anti-PD-1 and anti-PD-L1 drugs (pembrolizumab, atezolizumab) and anti-TROP2 drug (sacituzumab govitecan). 16 RCTs provided HR (95%CI) for PFS in the subgroup of Asians and 17 RCTs for Non-Asians."

IO biomarker • P3 data • Retrospective data • Review • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor

Disproportionality analysis of interstitial lung disease associated with novel antineoplastic agents during breast cancer treatment: a pharmacovigilance study. (PubMed, EClinicalMedicine) - "We identified 9 agents with reporting signals for ILD in FAERS: ROR and 95% confidence interval (CI) for trastuzumab deruxtecan was 12.17 (95% CI 11.04-13.41), atezolizumab 6.04 (5.02-7.28), everolimus 3.21 (2.95-3.50), abemaciclib 2.87 (2.52-3.27), pertuzumab 2.84 (2.49-3.25), olaparib 2.29 (1.65-3.19), trastuzumab emtansine 2.27 (1.91-2.69), pembrolizumab 2.06 (1.65-2.58), and trastuzumab 1.36 (1.25-1.49). These findings highlight the need for vigilant ILD monitoring but require validation through prospective studies to clarify true clinical risks. None."

Adverse events • Journal • Breast Cancer • Interstitial Lung Disease • Oncology • Pulmonary Disease • Respiratory Diseases • Solid Tumor

Novel humanized cell and murine models expressing tumor-associated antigens for ADC toxicity and IO combination evaluation (AACR 2025) - "Tumor-bearing models were treated with monotherapy of trastuzumab-deruxtecan (T-Dxd), sacituzumab govitecan or enfortumab vedotin, or combination therapy with anti-PD-1 antibodies. For the toxicity study, 180 mg/kg T-Dxd and 100 mg/kg trastuzumab-emtansine (T-DM1) were injected into hHER2 mice weekly for two doses by intravenous injection. A highly HER2-expressing HuCell line (clone #2) successfully grew in hHER2 models but not in WT models, with tumors displaying nearly 100% of human Her2 positive cells with high surface expression (2×105 molecules per cell)...Combination treatment of T-Dxd (4 mg/kg+2 mg/kg, QW) with Keytruda (5 mg/kg, BIW×2) resulted in a complete response rate (8/8) with 87% TGI (p<0.01) compared to T-Dxd monotherapy (7/8) with 96% TGI (p<0.001) in hHER2/PD-1 double knock in mice... HuCell and HuGEMM models provide an advanced platform to evaluate ADC drug monotherapy and combination therapies with immune checkpoint inhibitors...."

IO biomarker • Preclinical • Oncology • HER-2 • NECTIN4

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

Antibody-drug conjugates in breast cancer treatment: resistance mechanisms and the role of therapeutic sequencing. (PubMed, Cancer Drug Resist) - "While ADCs like trastuzumab emtansine (T-DM1), trastuzumab deruxtecan (T-DXd), and sacituzumab govitecan have shown significant efficacy, resistance mechanisms such as antigen loss, impaired internalization, and efflux of cytotoxic payloads challenge their effectiveness. The potential of combination therapies, such as ADCs with immune checkpoint inhibitors (ICIs), further highlights the evolving landscape of breast cancer treatment. As ADC technology advances, personalized approaches integrating biomarkers and optimized sequencing protocols offer promising avenues to enhance treatment outcomes and combat resistance in breast cancer."

IO biomarker • Journal • Review • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • 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

Utilizing endocytosis as a predictive biomarker for ADCs (AACR 2025) - "We are currently investigating the interplay between different ADCs and the endo/lysosomal machinery, and aim to develop this concept to a diagnostic tool for patients to be treated with ADCs. We use Trastuzumab emtansine, Trastuzumab deruxtecan and Sacituzumab Govitecan as model ADCs and evaluate the impact of different Rab GTPases on their mechanism of actions in cell lines from breast- and lung-cancer."

Biomarker • Breast Cancer • Lung Cancer • Oncology • Solid Tumor • HER-2 • RAB5A

Genomic and transcriptomic mediators of resistance to antibody-drug conjugates (ADCs) in metastatic breast cancer (MBC): A comprehensive multi-center study (AACR 2025) - "Three ADCs are US FDA-approved in MBC: sacituzumab govitecan (SG), trastuzumab deruxtecan (T-DXd) and trastuzumab emtansine (T-DM1), with many others in development. This might be related to the ADC MoA, particularly the payload release and bystander effect. Additional research is needed to validate these novel findings and the molecular underpinnings mediating resistance to ADCs."

Clinical • Metastases • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ABCB1 • ABCC1 • ABCC2 • HER-2 • TOP1

Comparison of activities and identification of predictive genomic biomarkers of response to trastuzumab and the trastuzumab deruxtecan ADC using the OncoPanel® platform (AACR 2025) - "In 2013, the first ADC approved for treating solid tumors was the Her2-targeted ado-trastuzumab emtansine, which was developed for metastatic breast cancer. In this study, we compare and contrast the potency and efficacy of each tested agent and explore the genomic biomarkers associated with sensitivity and resistance to each of these treatments. Additionally, we have also evaluated the effect of these agents from a broader tissue biology perspective, including use of the BioMAP® cellular phenotypic platform."

Biomarker • Breast Cancer • Colorectal Cancer • Gastric Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Lung Cancer • Oncology • Solid Tumor

Multi-modal assessment of an anti-HER2 (trastuzumab) antibody-drug conjugate screening assay for breast cancer models (AACR 2025) - "To overcome this, ADCs such as Trastuzumab-Emtansine (DM1) or Trastuzumab-Deruxtecan (Dxd) can be used at lower doses, reducing the risk of resistance and potentially enhancing treatment efficacy.Assessment of Trastuzumab ADCs in multiple murine breast cancer models can be costly, but in vitro evaluation of various cancer histotypes facilitates the selective identification of the best murine model. The ability of ADCs to target bystander cells suggest that even in heterogenous HER-2 expressing tumors, these therapies may still be effective. Our cutting-edge approaches provide precise insights into the activity and efficacy of Trastuzumab ADCs."

Preclinical • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor

Advanced models of breast cancer brain metastasis and imaging protocols for preclinical efficacy studies (AACR 2025) - "Transport of HER2 targeting trastuzumab across the BBB was confirmed by PET/MRI, resulting in a subsequent study evaluating efficacy of Trastuzumab emtansine (T-DM1) (ST1339 and ST3338)... We've successfully developed multiple complex orthotopic models for BCBM mimicking different aspects of BCBM. ICar and ICt models especially resemble the pathophysiology of BCBM to a large extent with extravasation and micro seeding in the brain. Together with the developed imaging protocols allowing longitudinal evaluation of compound delivery, tumor growth and BBB permeability this serves as a great platform for preclinical studies with novel anti-cancer agents."

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

ADC efficacy and safety evaluation based on organoid models (AACR 2025) - "Responses to four groups of HER2-targeted ADC drugs were evaluated in these models by assessing cell viability, including Trastuzumab deruxtecan, Trastuzumab duocarmazine, Trastuzumab emtansine, Trastuzumab MMAE, and their corresponding payloads (with or without linker). The HER2 expression levels in the in vitro cultured PDXO models were almost consistent at both RNA and protein levels, and they accurately reflected the expression status of the original tissues. The ADC screening revealed a differential sensitivity of organoids based on HER2 expression levels, with high HER2 expression correlating with increased sensitivity to ADC treatment, while low expression indicated resistance. Interestingly, normal organoid models were insensitive to ADC treatment, suggesting a potential for minimal side effects."

Clinical • Oncology • HER-2

Trastuzumab Emtansine(T-DM1) After Trastuzumab Deruxtecan(T-DXd) in HER2-Positive Breast Cancer in Korea (clinicaltrials.gov) - P=N/A | N=100 | Recruiting | Sponsor: Seoul National University Hospital

New trial • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor