Enhertu (fam-trastuzumab deruxtecan-nxki) / Daiichi Sankyo, AstraZeneca - LARVOL DELTA

Distinguishing on-target efficacy and off-target toxicity with antibody drug conjugates (ADCs) on diseased and normal hematopoietic cells (ASH 2025) - "Therefore, many ADCs, for example Trastuzumab-vc-MMAE (Enhertu) targeting specific diseased proteins (HER-2) which are not present on hematopoietic cells, may still have hematopoietic liabilities. Although this value was significantly different to that of Mylotarg on normal marrow progenitors, off-target toxicity was demonstrated. These data suggest that clonal assays with primary normal and diseased bone marrow cells may provide insight as to relative potency of an ADC on a disease-specific target as well as potential off-target toxicity to normal hematopoietic progenitors."

Clinical • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Neutropenia • Thrombocytopenia • CD33 • HER-2 • PTPRC

Molecular pathology of bladder cancer. (PubMed, Histopathology) - "Alterations in FGFR3, commonly found in the luminal-papillary molecular subtype associated with low response to immunotherapy, are the target of erdafitinib. Enfortumab vedotin, which targets Nectin-4 (expressed in >95% of urothelial carcinomas), is approved for patients who progress after chemotherapy and/or immunotherapy...Sacituzumab govitecan, an antibody-drug conjugate directed against Trop-2, is effective in basal, luminal and stroma-rich subtypes but not in neuroendocrine carcinomas. In addition, therapies developed for HER2-positive breast cancer have shown efficacy in urothelial carcinoma, with recent data from the DESTINY pan-tumour phase II trial leading to FDA approval of trastuzumab deruxtecan for HER2-overexpressing metastatic urothelial carcinoma. This paper is a comprehensive review of the molecular pathology of bladder cancer, highlighting advances in molecular classification, biomarkers and personalized therapies. The transition from morphology-based..."

Biomarker • IO biomarker • Journal • Review • Bladder Cancer • Breast Cancer • Endocrine Cancer • Genito-urinary Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Neuroendocrine Carcinoma • Oncology • Solid Tumor • Urothelial Cancer • FGFR3 • HER-2 • KDM6A • KMT2D • PIK3CA • RB1 • TP53

Effusion Reduction after Early Trastuzumab Deruxtecan Therapy for Unresectable HER2-Low Breast Cancer in an Older Patient: A Case Report. (PubMed, Surg Case Rep) - "T-DXd is potentially a safe and effective treatment option for older patients with HER2-low breast cancer and for those with impaired ADL. Further accumulation of cases and investigations of long-term outcomes are warranted."

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

Invited Discussant – Asian perspectives on DESTINY-Breast11: Neoadjuvant trastuzumab deruxtecan alone (T-DXd) or followed by paclitaxel + trastuzumab + pertuzumab (T-DXd-THP) vs SOC for high-risk HER2+ early breast cancer (eBC) (ESMO Asia 2025) - No abstract available

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

DESTINY-Breast11: Neoadjuvant trastuzumab deruxtecan alone (T-DXd) or followed by paclitaxel + trastuzumab + pertuzumab (T-DXd-THP) vs SOC for high-risk HER2+ early breast cancer (eBC) (ESMO Asia 2025) - No abstract available

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

Trastuzumab deruxtecan (T-DXd) + pertuzumab (P) vs taxane + trastuzumab + pertuzumab (THP) for first-line (1L) treatment of Asian patients (pts) with HER2+ advanced/metastatic breast cancer (a/mBC): A DESTINY-Breast09 analysis (ESMO Asia 2025) - P3 | "T-DXd + P demonstrated consistent efficacy as 1L treatment in Asian pts with HER2+ a/mBC, with no new safety signals. Table: 88MO Data in brackets are 95% CIs. *Estimate may change at updated analysis BICR, blinded independent central review; CI, confidence interval; DOR, duration of response; INV, investigator; mo, months; NC, not calculable; PFS, progression-free survival; ORR, objective response rate"

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

A new era in metastatic endometrial carcinoma: Integrating chemotherapy, immunotherapy, targeted therapy and antibody-drug conjugates (ESMO Asia 2025) - "This case illustrates an evolving treatment landscape, including the use of immunotherapy and trastuzumab deruxtecan (Tdxd) in the HER2 2+ setting...She received first line therapy with paclitaxel and carboplatin...She presented with disease progression in feb 2023, for which she received 2nd line pembrolizumab and lenvatinib till oct 2023... This case highlights the shifting treatment paradigm in advanced endometrial carcinoma, demonstrating how the sequential use of chemotherapy, immunotherapy, targeted therapy, and radiotherapy can extend disease control and improve survival. It highlights the potential role of Tdxd in HER2-low metastatic endometrial carcinoma, even in heavily pretreated patients. Careful toxicity monitoring is essential to optimize outcomes."

Metastases • Endometrial Cancer • Oncology • Solid Tumor • CCNE1 • ER • HER-2 • TP53

EMILIA and DESTINY: Real-World Sequencing Insights in a HER2-positive Metastatic Breast Cancer with Rare Pancreatic metastasis (ESMO Asia 2025) - "In an attempt to render her no evidence of disease (NED), MDT pursued mastectomy (ypTis) and chest wall radiotherapy, followed by maintenance trastuzumab pertuzumab 1 year...Gemcitabine bridging was administered during visceral crisis, after which trastuzumab emtansine (TDM-1) was commenced, achieving stable disease with marginal regression sustained over six cycles...Repeated biopsy was critical to exclude a second primary and reaffirm HER2 status, enabling optimal therapeutic choice. These observations support further investigation into post–T-DXd sequencing strategies and may inform management of biologically similar patient subgroups in ongoing and future trials."

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

Patient (pt) characteristics, HER2 testing, and treatment (Tx) patterns in advanced HER2 (ERBB2)-mutant (HER2m) NSCLC in real-world clinical practice (ESMO Asia 2025) - "In March 2019, AstraZeneca entered into a global development and commercialization collaboration agreement with Daiichi Sankyo for trastuzumab deruxtecan (T-DXd; DS-8201)... Median time from advanced NSCLC diagnosis to HER2 test result decreased between 2019 to 2022, suggesting HER2 testing practices improved over time. Chemotherapy only was the most common Tx used across all LOT; targeted Tx regimens, including HER2-directed Tx, were more frequently used in later LOT, possibly reflecting changes in evidence and Tx availability during the study period. Although low pt numbers receiving 3L Tx limit interpretation, data provide valuable insights into HER2 testing and Tx patterns in advanced HER2m NSCLC."

Clinical • Metastases • Real-world • Real-world evidence • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • HER-2

Patient-reported outcome measures for toxicities and HRQoL in cancer patients treated with antibody-drug conjugates: A systematic review (ESMO Asia 2025) - "Unique toxicities were reported, such as keratopathy with belantamab mafodotin, for which OSDI was used in the DREAMM-2 study, and dysgeusia with enfortumab vedotin, assessed using CiTAS in one observational study...In the DESTINY-Breast series, trastuzumab deruxtecan was associated with interstitial lung disease, yet no PROM is currently available to monitor this toxicity. Current PROMs are not tailored to the unique toxicity profiles of ADCs. Current PROMs are not tailored to the unique toxicity profiles of ADCs. There is an urgent need to develop and validate tools that capture symptoms such as ocular toxicity, pulmonary toxicity, and dysgeusia. Integrating these instruments into clinical trials and routine care will improve toxicity monitoring and enable more accurate, patient-centered quality-of-life assessments."

Clinical • Patient reported outcomes • Review • Brain Cancer • Breast Cancer • Glioblastoma • Hematological Malignancies • Lymphoma • Multiple Myeloma • Oncology • Ovarian Cancer • Solid Tumor • Urothelial Cancer

First-line (1L) trastuzumab deruxtecan (T-DXd) 5.4 mg/kg + fluoropyrimidine (FP) + pembrolizumab (pembro) in advanced HER2+ gastric cancer (GC), gastroesophageal junction adenocarcinoma (GEJA), or esophageal adenocarcinoma: updated results from DESTINY-Gastric03 (DG-03) Part 2F (ESMO Asia 2025) - P2 | "In arm 2F, pts received T-DXd 5.4 mg/kg IV Q3W + reduced-dose FP (5-fluorouracil 600 mg/m2/day, CIV, Days 1–5 Q3W or capecitabine 750 mg/m2, BID, Days 1–14 Q3W) + pembro 200 mg IV Q3W. Results provide further evidence of antitumor activity with 1L T-DXd 5.4 mg/kg + reduced-dose FP + pembro in HER2+ GCs, with no new safety signals observed; ORRs were consistent irrespective of PD-L1 status. Data support the ongoing studies with this 1L T-DXd triplet regimen in HER2+ GCs."

Clinical • Metastases • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Oncology • Solid Tumor • HER-2 • PD-L1

Preliminary efficacy and safety of TQB2102 in HER2-positive locally advanced unresectable or metastatic biliary tract cancer: Phase Ib study results (ESMO Asia 2025) - P1/2 | "Notably, in Cohort 1, the ORR was 28.6% (95% CI: 3.7–71.0) in pts with prior anti-HER2 therapy( Trastuzumab,Pertuzumab,DS-8201) and 50% (95% CI: 6.8–93.2) in HER2 IHC 2+ and ISH+ pts. TQB2102 demonstrated favorable tolerability and encouraging antitumor activity in HER2-positive locally advanced/metastatic BTC. The 7.5 mg/kg dose showed superior efficacy versus 6.0 mg/kg and is therefore recommended as the RP2D for BTC. The Phase 2 study is currently in preparation."

Clinical • Metastases • P1 data • Biliary Cancer • Biliary Tract Cancer • Oncology • Solid Tumor • CD4 • HER-2

HydroLock: A versatile ADC platform with robust plasma stability, excellent bystander killing and superior in vivo efficacy (ESMO Asia 2025) - "Efficacies of Herceptin-GSC4903 and the potential to overcome DS8201 resistance were determined...We also conjugate eribulin to pertuzumab (Pertuzumab-GSC4781)... All these results warrant HydroLock as a novel and promising linker-payload platform for ADC development. HydroLock was leveraged in several bispecific ADC programs and the first IND submission is expected in late 2025."

Preclinical • Oncology

HERTHENA-Breast01: A phase Ib/II, multicenter, open-label, dose-finding study to evaluate the safety and antitumor activity of patritumab deruxtecan (HER3-DXd) in HER2+ advanced breast cancer (BC) (ESMO Asia 2025) - P1/2 | "Background: Although HER2-targeted antibody-drug conjugates (ADCs) have improved outcomes in HER2+ advanced BC, safe and effective later-line therapies are needed for patients who have progressed on trastuzumab deruxtecan (T-DXd)...Pts in Arms 2 and 3 receive the same regimen as Arm 1, with either pertuzumab 840 mg IV followed by 420 mg IV Q3W (Arm 2) or tucatinib 300 mg orally BID (Arm 3)...Secondary endpoints are pharmacokinetics of HER3-DXd ADC, total HER3-DXd antidrug antibody and free DXd payload. Enrollment began in early 2025."

Clinical • Metastases • P1/2 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • ERBB3 • HER-2

HER2 and TROP2 antibody–drug conjugates in metastatic breast cancer: A systematic review of clinical outcomes (ESMO Asia 2025) - "Background: Antibody-drug conjugates (ADCs) targeting HER2 (trastuzumab emtansine [T-DM1], trastuzumab deruxtecan [T-DXd]) and TROP2 (sacituzumab govitecan [SG]) offer novel treatment opportunities for patients with metastatic breast cancer (mBC). HER2- and TROP2-targeting ADCs demonstrate meaningful survival benefits across different metastatic breast cancer subtypes with manageable toxicity profiles. T-DXd shows improved efficacy over T-DM1 in HER2-positive mBC patients, while SG demonstrates clinical benefit in triple-negative and HR+/HER2-negative populations."

Clinical • Clinical data • Metastases • Review • 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

Segregating HER2-low metastatic breast cancer into positive-like and zero-like subgroups using a transcriptomic HER2 signature (ESMO Asia 2025) - "Background: HER2-low metastatic breast cancer (mBC) has gained clinical relevance following trastuzumab-deruxtecan approval, yet its biological distinctiveness remains debated... A 17-gene signature refines HER2-low mBC more precisely into positive-like and zero-like subgroups, revealing a continuum of HER2 activity. Alternative signaling pathways may underlie HER2 activity in HER2-low positive-like versus zero-like mBC."

Metastases • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • GRB7 • HER-2 • MBD4 • MED1 • MIEN1

Preliminary analysis for baseline characteristics and treatment patterns of trastuzumab deruxtecan in Chinese patients with HER2-positive and HER2-low breast cancer: First interim analysis of REFRESH study (ESMO Asia 2025) - P | "This analysis provides insights into the real-world treatment patterns and patient characteristics of T-DXd use in Chinese patients with BC in clinical practice. T-DXd is emerging as a practice changing therapy in China clinical practice, now being prescribed earlier, as HER2+ mBC enters first-line treatment and HR+/HER2-low mBC receives T-DXd before chemotherapy."

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

Real-world incidence of interstitial lung disease and cardiotoxicity with trastuzumab deruxtecan in metastatic breast cancer: Qatar's national experience (ESMO Asia 2025) - "Real-world ILD/pneumonitis and cardiotoxicity rates with T-DXd were consistent with pivotal trials. Vigilant monitoring enables early detection, effective management, and safe treatment continuation in selected patients."

Clinical • Metastases • Real-world • Real-world evidence • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Efficacy and safety of trastuzumab deruxtecan (T-DXd) in HER2-positive (HER2+) advanced breast cancer (ABC) with CNS progression after local treatment: Real-world data (ESMO Asia 2025) - "Median lines of previous treatment in ABC was four (1-8), 47 (84%) pts have received pertuzumab, T-DM1 – 45 (80%) pts, lapatinib – 22 (39%) pts; all 3 anti-HER2 Rx received 15 (27%)pts. T-DXd is effective even in pts with CNS progression previously treated with radiation therapy. No new safety signals were recorded."

Clinical • Metastases • Real-world • Real-world evidence • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Collaborations Supporting Innovation in Breast Cancer ResearchCollaborations Supporting Innovation in Breast Cancer Research (Businesswire) - "Two spotlight poster presentations will report interim results from the HALLOW prospective observational trial (PD13-11) evaluating the efficacy and safety of ENHERTU in patients with HER2 low (IHC 1+ or 2+/ISH-) metastatic breast cancer with and without active brain metastases in Japan, and a post-hoc pooled efficacy analysis (PD13-10) from the TUXEDO-3 phase 2 trial of patritumab deruxtecan (HER3-DXd)...Two poster presentations will report on the intracranial and/or extracranial activity of ENHERTU and DATROWAY. A translational ctDNA analysis of intracranial and extracranial activity (PS2-08-20) of ENHERTU from the DEBBRAH phase 2 trial in patients with HER2 positive and HER2 low breast cancer with leptomeningeal disease will be highlighted, as well as results of intracranial activity (PS1-09-02) of DATROWAY from the DATO-BASE phase 2 trial in patients with HER2 negative breast cancer with leptomeningeal disease."

Clinical data • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer

MEDSIR's activity at SABCS 2025 has also included the presentation of the…CEBBRAH studies. (PRNewswire) - "During the congress, MEDSIR also presented the results of the CEBBRAH translational analysis, which evaluates for the first time the presence of ctDNA in both plasma and cerebrospinal fluid of patients with HER2+ breast cancer and leptomeningeal disease treated with T-DXd. The patients who, after receiving T-DXd, showed a reduction of ctDNA in the cerebrospinal fluid presented better control of the leptomeningeal disease, which supports its possible role as a biomarker of the disease."

Clinical data • HER2 Positive Breast Cancer

Advances in breast cancer: PONTIAC… (PRNewswire) - "PONTIAC is a Phase II trial evaluating the efficacy and safety of the use of trastuzumab deruxtecan (T-DXd) as a first-line treatment for patients with HR+/HER2-low/ultralow breast cancer and a non-luminal genomic subtype."

Clinical protocol • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer

Comparative effectiveness of trastuzumab deruxtecan versus real-world treatment in HER2-amplified advanced solid tumors detected by cell-free DNA: An exploratory analysis of the HERALD trial and GOZILA study. (ASCO-GI 2026) - "The full, final text of this abstract will be available on Jan 05 at 05:00 PM EST."

Cell-free DNA • Clinical • HEOR • Metastases • Real-world • Real-world evidence • Gastrointestinal Cancer • Oncology • Solid Tumor • HER-2

Exploratory analysis of HER2 status based on central and local testing results from the DESTINY-Gastric04 study. (ASCO-GI 2026) - P3 | "In March 2019, AstraZeneca entered into a global development and commercialization collaboration agreement with Daiichi Sankyo for trastuzumab deruxtecan (T-DXd; DS-8201a). Clinical Trial Registration Number: NCT04704934 The full, final text of this abstract will be available on Jan 05 at 05:00 PM EST."

Esophageal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • HER-2

Efficacy and safety of trastuzumab deruxtecan in HER2-positive advanced gastric and gastroesophageal junction cancers: A meta-analysis of real-world studies and clinical trials. (ASCO-GI 2026) - "The full, final text of this abstract will be available on Jan 05 at 05:00 PM EST."

Metastases • Real-world • Real-world evidence • Retrospective data • Esophageal Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor • HER-2