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

Impact of trastuzumab deruxtecan (T-DXd) and brain stereotactic radiosurgery on intracranial control and radionecrosis risk in HER2-positive or -low breast cancer brain metastases. (PubMed, Breast) - "Combining T-DXd with SRS demonstrated a favorable safety profile without increasing the risk of radionecrosis. Furthermore, this combination was associated with superior intracranial control, encompassing both local and distant outcomes, supporting the potential of T-DXd combined with SRS as an effective and well-tolerated approach for HER2-positive or -low BCBM."

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

Trastuzumab deruxtecan (T-DXd) vs trastuzumab emtansine (T-DM1) in patients (pts) with high-risk human epidermal growth factor receptor 2–positive (HER2+) primary breast cancer (BC) with residual invasive disease after neoadjuvant therapy (tx): Interim analysis of DESTINY-Breast05 (ESMO 2025) - P3 | "Conclusions T-DXd showed a statistically significant and clinically meaningful IDFS and DFS benefit vs T-DM1, extending its superiority to post-neoadjuvant residual disease in pts with HER2+ early BC, and representing a potential new SOC. Safety of T-DXd was generally manageable with no new safety signals."

Clinical • Late-breaking abstract • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Trastuzumab botidotin vs trastuzumab emtansine (T-DM1) in HER2-positive unresectable or metastatic breast cancer: Results from a randomized phase III study (ESMO 2025) - P3 | "Results A total of 365 pts were randomized (median age 55 years; 73.4% with visceral metastases; 53.4% received ≥2 prior anti-HER2 therapies; 55.9% had prior pyrotinib). Conclusions A166 demonstrated statistically significant and clinically meaningful improvement in PFS compared with T-DM1, with a manageable safety profile in pts with HER2+ unresectable or metastatic BC. These results position A166 as a potential new therapeutic option for HER2+ disease."

Clinical • Late-breaking abstract • Metastases • P3 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

MRI-based personalisation of neoadjuvant chemotherapy duration in HER2-positive early breast cancer (TRAIN-3): primary results from a multicentre, single-arm, phase 2 study. (PubMed, Lancet Oncol) - P2 | "MRI-guided optimisation of neoadjuvant chemotherapy duration was associated with favourable 3-year event-free survival outcomes in patients with stage II-III HER2-positive breast cancer. This approach represents a novel strategy that reduces treatment burden, minimises toxicity, and preserves quality of life in a subset of patients with early HER2-positive breast cancer."

Journal • P2 data • Breast Cancer • Hematological Disorders • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Neutropenia • Oncology • Pain • Solid Tumor • Thrombocytopenia • HER-2

Efficacy and safety of DP303c versus T-DM1 in HER2-positive advanced breast cancer: Interim analysis of a randomized, open-label, phase 3 trial (SABCS 2025) - "Pts were stratified by number of lines of previous systemic therapy (≤1 vs. >1), prior pertuzumab treatment (Yes vs. No), and visceral metastasis(Yes vs. No). DP303c demonstrated statistically significant and clinically meaningful improvement in PFS compared with T-DM1 in pts with HER2+ ABC who had been previously treated with trastuzumab and taxane. The safety profile of DP303c was manageable. These results support DP303c as a potential new treatment option for HER2+ ABC."

Clinical • Metastases • P3 data • P3 data: top line • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Real-world clinical, molecular, treatment patterns and outcomes of HER2-altered lung cancer from community oncology centres in Western India (ELCC 2026) - "mOS was 26 months with T-DM1 vs 16.9 months with trastuzumab p=0.008. mOS was reported as 6months for T-Dxd.Conclusions This study delineates the real-world molecular landscape, treatment utilization & clinical outcomes of HER2-altered lung cancer managed in Indian community oncology settings."

Clinical • Real-world • Real-world evidence • Lung Cancer • Oncology • Solid Tumor • EGFR • HER-2 • KRAS • TP53

Trastuzumab Deruxtecan in Residual HER2-Positive Early Breast Cancer. (PubMed, N Engl J Med) - P3 | "In patients with high-risk, residual invasive HER2-positive breast cancer, postneoadjuvant T-DXd resulted in a significantly higher likelihood of invasive disease-free survival than T-DM1; toxic effects were mainly gastrointestinal and hematologic. An important identified risk of T-DXd is interstitial lung disease, which requires appropriate monitoring and management. (Funded by Daiichi Sankyo and AstraZeneca; DESTINY-Breast05 ClinicalTrials.gov number, NCT04622319.)."

Journal • Breast Cancer • Constipation • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • HER2 Breast Cancer • HER2 Positive Breast Cancer • Interstitial Lung Disease • Oncology • Pulmonary Disease • Respiratory Diseases • Solid Tumor • HER-2

IL Believe: A Study to Investigate Safety and Tolerability of TransCon IL-2 β/γ Alone or in Combination With Pembrolizumab and/or TransCon TLR7/8 Agonist or Other Anticancer Therapies in Adult Participants With Locally Advanced or Metastatic Solid Tumor Malignancies (clinicaltrials.gov) - P1/2 | N=320 | Active, not recruiting | Sponsor: Ascendis Pharma Oncology Division A/S | Recruiting ➔ Active, not recruiting

Enrollment closed • First-in-human • Breast Cancer • Cervical Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Small Cell Lung Cancer • Solid Tumor • CTLA4

Prediction of survival after de-escalated neoadjuvant therapy in HER2+ early breast cancer: A pooled analysis of three WSG trials. (ASCO 2025) - P2, P2/3 | "WSG-ADAPT-HR-/HER2+ (NCT01817452) compared trastuzumab and pertuzumab (T + P, n=92) vs. T +P + pac (n=42); WSG-ADAPT-HR+/HER2+ (NCT01779206) compared trastuzumab emtansine (T-DM1, n=118) vs. T-DM1 + standard endocrine therapy (ET, n=125) vs. T + ET (n=129); WSG-TP-II (NCT03272477) compared neoadjuvant/adjuvant T + P + ET (n=100) vs. T + P + pac (n=107). This pooled analysis demonstrates that de-escalation trials in HER2+ eBC are feasible and safe for patients. 12× weekly paclitaxel + HER2 blockade is an effective and well-tolerated regimen with excellent 5-year survival. The favorable survival after pCR to sCTx-free NAT lays the groundwork for further de-escalation strategies, such as the currently ongoing WSG-ADAPT-HER2-IV evaluating T-DXd as NAT."

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

Trastuzumab deruxtecan (T-DXd) vs trastuzumab emtansine (T-DM1) in patients with high-risk human epidermal growth factor receptor 2-positive (HER2+) primary breast cancer (BC) with residual invasive disease after neoadjuvant therapy: Interim analysis of DESTINY-Breast05 (SABCS 2025) - P3 | "The additional analyses further characterize the positive benefit of T-DXd over T-DM1 in the post-neoadjuvant HER2+ BC residual disease setting, supporting T-DXd as a potential new standard-of-care in this setting. Timing of adjuvant RT did not impact incidence of adjudicated drug-related ILD with T-DXd. Additional results will be presented.Table."

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

Breast cancer organoids as a complementary preclinical model to PDX, enabling immunotherapy evaluation (AACR 2026) - "We further evaluated responses to HER2-targeted therapies using trastuzumab-emtansine (T-DM1) in two pairs of PDX and PDXO models differing in HER2 expression... The establishment of a mirror biobank comprising matched PDX and PDXO models enables acceleration of early-stage drug screening and seamless in vivo validation using corresponding PDXs. Beyond pharmacological testing, organoids offer an advantage by facilitating the evaluation of immunotherapeutic strategies. Together, these complementary models provide powerful translational tools for the development of novel breast cancer therapies and open new avenues for advancing immunotherapy research."

IO biomarker • Preclinical • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • TP53

Next-generation human vascularized tumor models reveal HER2-independent efficacy and reduced vascular toxicity of T-DXd (AACR 2026) - "Human vascularized tumor models capture key pharmacodynamic features of ADCs, including the HER2-independent mechanism of action, extracellular payload activity, and vascular toxicity, which are not recapitulated in 2D systems. HER2-independent efficacy of T-DXd, but not of T-DM1, has also been reported in in vivo breast cancer xenograft models in agreement with these findings. Furthermore, real-time monitoring enabled quantification of tumor regression and vascular remodelling, underscoring the functional relevance and predictive performance of the platform."

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

Safety, tolerability, and early immune responses in the safety run-in of an HER2 multi-epitope vaccine combined with T-DM1 in residual HER2-positive breast cancer (AACR 2026) - "Concurrent administration of H2NVAC with T-DM1 was safe and did not increase toxicity beyond single-agent T-DM1. To our knowledge, this is the first study to demonstrate that a cancer vaccine can be delivered concurrently with an antibody-drug conjugate without increasing adverse effects while still eliciting robust T-cell responses. Ongoing analyses will further define the kinetics and durability of vaccine-induced antibody and T-cell responses at later time points, as well as evaluate the efficacy of H2NVAC in reducing recurrence risk in the randomized phase 2 trial."

Clinical • IO biomarker • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • CD4 • CD8 • HAVCR2 • HER-2 • IFNG • IGFBP2 • LAG3 • MB

Real-time, label-free assessment of HER2-targeted antibody-drug conjugate therapies (AACR 2026) - "As expected, impedance data showed that DS-8201a had enhanced cytotoxic effects on the high HER2-expressing SKOV3 cells compared to the other two cell types with lower HER2 expression. Finally, we compared the cytotoxic effects of DS-8201a to another trastuzumab-based ADC, trastuzumab-emtasine (T-DM1, branded as Kadcyla®) on the Maestro Z. Taken together, these results show that the cytotoxic capacity of ADC therapies toward HER2 positive cell types can be screened using the Maestro Z. The assay presented here can be used to further develop ADC therapies aimed at HER2-positive cancers as well as ADCs toward other cancer-specific targets."

ADC • Oncology • HER-2

Fully human anti-HER-2 antibodies to HER-2 domains distinct from trastuzumab as antibody drug conjugates for tumor growth inhibition (AACR 2026) - "While first FDA approved as a naked antibody, it is at the basis of the development of several antibody drug conjugates bearing different linker and payloads such Ado-Trastuzumab-Emtansine (Kadcyla) and fam-trastuzumab-deruxtecan-nhki (Enhertu). Two trastuzumab noncompeting antibodies were further characterized for their ability to inhibit proliferation in vitro and in vivo in mouse xenografts studies and to potentiate trastuzumab effect. Our data also demonstrates that the use of fully human mice constitutes a powerful approach to develop fully human monoclonal antibodies against cancer targets allowing to by-pass the need for humanization and affinity maturation of antibodies."

ADC • Gastric Cancer • Oncology • Solid Tumor

Clonal evolutionary trajectory of HER2-positive breast cancer with ERBB2 or PIK3CA mutations under neoadjuvant treatment (AACR 2026) - "In this study, we profiled the multi-omics landscape of ERBB2- and PIK3CA-mutant tumors from the randomized PREDIX HER2 trial, which compared neoadjuvant trastuzumab emtansine (T-DM1) with dual HER2 blockade plus chemotherapy in early-stage HER2-positive disease. Fresh-frozen tumor biopsies were used for RNA sequencing and whole-exome sequencing (WES), while FFPE biopsies were used for Xenium 5K spatial transcriptomics... This longitudinal evolutionary analysis of ERBB2- or PIK3CA-mutant, HER2+ breast cancer suggests that tumors evolve heterogeneously under HER2-targeted therapies, revealing the positive selection of pathogenic ERBB2 and PIK3CA mutations."

Clinical • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • FGF21 • HER-2 • KLB • PIK3CA

Enhancing the predictability of human pharmacokinetics for antibody-drug conjugates (ADCs) using human FcRn transgenic mice (AACR 2026) - "This study evaluates hFcRn and HSA/hFcRn transgenic mice using marketed ADCs to establish their role in translational DMPK assessment.Methods Four ADCs (T-DXd, T-DM1, SG, EV) were administered intravenously (10 mg/kg) to C57BL/6 WT, hFcRn, and HSA/hFcRn mice. Please find the comparison of PK parameters in the table 1.Furthermore, the platform successfully differentiated the stability characteristics between ADCs with stable (T-DXd) and more labile (EV) linkers, providing insights into ADC structure complexity and PK relationships.Conclusion This study demonstrates that hFcRn transgenic mouse model accurately recapitulates human-relevant PK profiles that directly address a major limitation of conventional WT mouse models. The implementation of this platform enables more reliable human PK predictions and informs FIH trial design, and also provides a strategic approach to de-risking ADC development through data-driven candidate selection, reducing early discovery and..."

ADC • PK/PD data • Preclinical • Oncology

Integrative analysis of proteomic, transcriptomic, and FACS-based surface marker data for ADC target discovery in cancer cell lines (AACR 2026) - "We also established a multi-omics strategy integrating transcriptomic and proteomic data to enhance target characterization. Finally, we explored the relationship between protein expression of the targets and drug sensitivity by analyzing ADC targets in the context of responses to clinically approved ADCs, including trastuzumab emtansine (Kadcyla), and sacituzumab govitecan."

ADC • Preclinical • Oncology • HER-2 • TACSTD2

HER2 ADC resistance driven by IL-17 signaling and ROR1 upregulation: Overcoming DS-8201 resistance with BRY812 and BR111 (AACR 2026) - "Literature research revealed possible mechanism includes tumor microenvironment remodeling, enhanced cell survival, and immune evasion.BRY812 (an anti-LIV1 ADC conjugated to MMAE) and BR111 (an anti-ROR1 ADC conjugated to eribulin) are novel ADCs that have shown potent antitumor activity in various solid tumors. Further investigation revealed that treatment with HER2-targeting ADCs (DS-8201 and T-DM1) dose-dependently upregulated ROR1 expression, providing a potential mechanism for BR111's efficacy in this resistant setting. In conclusion, our research findings collectively revealed DS-8201 resistance mechanism and provided evidence that BRY812 and BR111 can overcome DS-8201 resistance."

ADC • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Lung Cancer • Oncology • Solid Tumor • CXCL1 • HER-2 • IL17A • ROR1

Systematic mechanistic profiling of ADC-resistant cancer cell lines (AACR 2026) - "To further unravel the underlying drug resistance mechanisms, we applied RNA-Seq and global proteomics profiling on several resistant models paired with their parental controls, including HCC1954 and NCI-N87 Enhertu-resistant, HCC1806 and Colo-205 Trodelvy-resistant cells...Subsequent cross-drug sensitivity profiling revealed that HCC1954 Enhertu-resistant cells were resistant to the other two HER2-targeting ADCs, T-DM1 and RC48 rather than their respective payloads, which further consolidated that reduction of HER2 expression other than any adaptive resistance to payload plays a pivotal role in the HCC1954 Enhertu-resistant model. Interestingly, we didn't observe any robust reduction of antibody target expression in the other three ADC resistant models, implying diverse resistance mechanisms across different ADCs and cancer cell lines. We will continue to do datamining and validation on these models in the near future, aiming to shed light on more ADC resistance..."

ADC • Preclinical • Oncology • HER-2

Overcoming acquired and intrinsic resistance with an integrated ADC platform (AACR 2026) - "An Her2- and Trop2-positive gastric PDX shown clear resistance (TGI < 10%) to trastuzumab deruxtecan and sacituzumab govitecan, two clinically used Her2 and Trop2 ADCs respectively, limited response (TGI 10-30%) to Herceptin and no response to Dxd treatment. In addition, the well-known ocular toxicity associated with multiple clinically used ADCs can be recapitulated by a cell-based assay using human corneal epithelial cells. On this platform, belantamab mafodotin, trodelvy and T-DM1 demonstrated consistent high, medium and low cytotoxicity respectively.The integration of above-mentioned platforms facilitates a deep understanding of resistance mechanisms and promotes the development of ADCs that are better aligned with clinical needs, with the ultimate goal of overcoming resistance."

ADC • IO biomarker • Oncology • HER-2

B836: A novel bispecific antibody-drug conjugate (ADC) as a clinical candidate to overcome trastuzumab deruxtecan resistance (AACR 2026) - "Resistance to single-antigen HER2-targeted ADCs, such as Enhertu (trastuzumab deruxtecan, DS-8201) and Kadcyla (trastuzumab emtansine, T-DM1), poses a significant challenge in HER2-positive cancers, often due to tumor heterogeneity and antigen downregulation. Furthermore, no systemic toxicity was detected at doses up to 5 mg/kg. These collective findings support the continued clinical development of B836, promising therapeutic potential in oncology."

ADC • Bispecific • Clinical • Oncology • HER-2

An integrated DMPK and bioanalytical platform for comprehensive characterization of antibody-drug conjugates (ADCs) (AACR 2026) - "Here, we present an integrated DMPK platform evaluating Trastuzumab Deruxtecan (T-DXd), Enfortumab Vedotin (EV), and Trastuzumab Emtansine (T-DM1), with distinct linkers/payloads, to delineate PK behavior and biotransformation pathways. For three marketed ADCs, including T‑DXd, EV, and T‑DM1, in vitro plasma stability was assessed in human, monkey, rat, and mouse plasma (37 °C, 7-21 days) and followed a single 10 mg/kg i.v. dose for in vivo PK in naïve C57BL/6 mice. Our integrated DMPK platform provides comprehensive and robust ADC characterization capability, promoting critical insights into ADC stability, biotransformation, and exposure profiles. This supports direct correlation between ADC design, in vitro properties, and in vivo PK behavior, thereby de-risking candidate selection and accelerating the development of novel ADC therapeutics."

ADC • Oncology

Site-specific dual-payload antibody conjugation enhances antitumor efficacy (AACR 2026) - "A trastuzumab-based ADC carrying DM1 (DAR 2) and seco-DUBA (DAR 2) demonstrated potent inhibition of JIMT-1 xenograft tumors, a model known to be resistant to T-DM1. Additionally, a dual-payload MMAE/exatecan ADC (DAR 2+2) achieved antitumor activity comparable to T-DXd (DAR 8), despite using substantially lower total payload. These results show the versatility and therapeutic potential of our dual-payload site-specific conjugation strategy. The platform provides a method to overcoming drug resistance and expanding therapeutic windows for next-generation ADCs."

Clinical • Oncology • HER-2

Quantitative analysis of microtubule lattice damage in NF1-deficient HER2-positive breast cancer under mitotic and pharmacological stress (AACR 2026) - "This in turn causes mitotic defects (potentially contributing to tumorigenesis) but also sensitization to maytansinoids like DM1, a drug class frequently used in Antibody-Drug Conjugates (ADC, T-DM1 and Mirvetuximab Soravtansine). EB1 shaft localization and mitotic defects (chromosome missegregation, aneuploidy) were rescued by NF1 re-expression.By establishing a quantitative framework to measure EB1 redistribution at single MT resolution, our study provides a previously unavailable strategy to monitor intra-lattice damage in cancer cells. These findings establish for the first time a direct causative link between unrepaired MT damage and chromosomal instability, providing a new model to understand maytansinoid mechanism of action."

Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2 • LASP1 • NF1