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

Molecular landscape of HER2-mutated non-small cell lung cancer in Northeastern Brazil: Clinical, histopathological, and genomic insights. (PubMed, Oncotarget) - "Treatment responses varied, with one patient receiving trastuzumab deruxtecan. Our findings highlight the molecular diversity and diagnostic challenges of HER2-mutated NSCLC in underrepresented populations, emphasizing the need for comprehensive molecular profiling and expanded access to targeted therapies."

Biomarker • Journal • Retrospective data • Tumor mutational burden • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • HER-2 • KRAS • STK11 • TMB • TP53

UCCL-IKF-NeoART - An international phase Ib/II trial investigating trastuzumab-deruxtecan (T-DXd) combined with neoadjuvant chemotherapy (Ctx) for HER2-positive, resectable esophagogastric adenocarcinoma (EGA) (ESMO-GI 2025) - No abstract available

Clinical • P1/2 data • Esophageal Cancer • Gastric Adenocarcinoma • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Oncology • Solid Tumor • HER-2

Study of Trastuzumab Deruxtecan Versus Standard of Care Chemotherapy for HER2-Expressing (IHC 3+/2+) Endometrial Cancer (clinicaltrials.gov) - P3 | N=710 | Not yet recruiting | Sponsor: Daiichi Sankyo

New P3 trial • Endometrial Cancer • Oncology • Solid Tumor

A Phase II Study of HLX22 in Combination With Trastuzumab Deruxtecan in HER2-low, Hormone Receptor Positive Locally Advanced or Metastatic Breast Cancer Patients (clinicaltrials.gov) - P2 | N=50 | Recruiting | Sponsor: Shanghai Henlius Biotech | Not yet recruiting ➔ Recruiting

Enrollment open • Breast Cancer • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor

PET imaging and optimization of HER2 modulation in HER2-low breast tumors to enhance therapeutic efficacy (SNMMI 2025) - "HER2 PET is predictive of subsequent drug response within weeks of therapy initiation and enables monitoring HER2 in tumors treated with T-DXd (Figure 1A). 89Zr-labeled trastuzumab and 64Cu-labeled trastuzumab enables imaging of tumors with varying HER2 protein levels (Figure 1B), including HER2-low tumors (Figure 1C). Tumors depleted of CAV-1 showed higher trastuzumab uptake when compared with control tumors."

Clinical • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • CAV1 • HER-2

HER2 PET Imaging to Assess HER2 Heterogeneity and Predict Reponse to Trastuzumab-Deruxtecan in HER2-low Breast Cancer (SNMMI 2025) - "Sponsored by Mars Shot"

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

An open-label, randomized, multicenter, phase III study of trastuzumab deruxtecan (T-DXd) with bevacizumab (BEV) vs BEV monotherapy as first-line (1L) maintenance therapy in HER2-expressing ovarian cancer: DESTINY-Ovarian01 (DO 01) (ESMO-GC 2025) - P3 | "Legal entity responsible for the study Daiichi Sankyo, Inc. In March 2019, AstraZeneca entered into a global development and commercialization collaboration agreement with Daiichi Sankyo for trastuzumab deruxtecan (T-DXd; DS-8201)."

Clinical • Monotherapy • P3 data • Oncology • Ovarian Cancer • Solid Tumor • HER-2

Beamion BCGC-1: A Study to Find a Suitable Dose of Zongertinib Used Alone and in Combination With Other Treatments to Test Whether it Helps People With Different Types of HER2+ Cancer That Has Spread (clinicaltrials.gov) - P1/2 | N=582 | Recruiting | Sponsor: Boehringer Ingelheim | Trial completion date: Aug 2028 ➔ Sep 2029 | Trial primary completion date: Feb 2027 ➔ Sep 2029

Trial completion date • Trial primary completion date • Breast Cancer • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Adenocarcinoma • Gastric Cancer • Gastroesophageal Cancer • Gastroesophageal Junction Adenocarcinoma • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor

DAISY: Study of DS-8201a, an Antibody Drug Conjugate for Advanced Breast Cancer Patients, With Biomarkers Analysis (clinicaltrials.gov) - P2 | N=186 | Completed | Sponsor: UNICANCER | Active, not recruiting ➔ Completed | Trial completion date: Apr 2025 ➔ Dec 2024

Biomarker • Trial completion • Trial completion date • 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 • ER • HER-2 • PGR

Trastuzumab Deruxtecan in Previously Treated HER2-Low Metastatic Breast Cancer: Real-World Multicentric Study in the Portuguese Population (Multidisciplinary Digital Publishing Institute) - "The study included 35 patients (34 female and 1 male patient), with a median age of 54 years at the start of T-DXd. All patients had an ECOG-PS 0–1, and 26 patients (74%) had hormone receptor (HR)-positive disease. The median number of prior lines of treatment was 4 [1–7], and 23 patients (65.8%) had metastases in three or more sites. With a median follow-up of 7.8 months, rwPFS was 6 months (95% CI, 2.3–9.7), and OS was 15 months (95% CI, 4.7–25.3). In HR-positive patients, the median rwPFS was 6 months (95% CI, 1.2–10.7), compared to 4 months (95% CI, 2.1–5.9) in HR-negative patients. The overall ORR was 52.9%."

Retrospective data • HER2 Breast Cancer

Association of HER2-low with clinicopathological features in patients with early invasive lobular breast cancer: an international multicentric study. (PubMed, Breast Cancer Res) - "HER2-low is present in more than half of the patients with early ER+ HER2- pure ILCs and is associated with larger tumor size and multifocality. HER2-low is associated with a worse DFS and OS as compared to HER2 0."

Biomarker • Journal • Retrospective data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • ER • HER-2

Analytical and clinical validation of PATHWAY HER2 (4B5) assay for assessment of HER2-low/HER2-ultralow status and eligibility for trastuzumab deruxtecan in DESTINY-Breast06. (PubMed, ESMO Open) - "For patients with HER2 IHC 0 mBC, rescoring and/or retesting with the Roche HER2 4B5 assay is encouraged to determine eligibility for T-DXd."

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

Advancing Antibody-Drug Conjugates: Precision Oncology Approaches for Breast and Pancreatic Cancers. (PubMed, Cancers (Basel)) - " In TNBC, ADCs such as sacituzumab govitecan and trastuzumab deruxtecan have improved progression-free survival in advanced cases. While ADCs have significantly advanced treatment options in TNBC, PDAC remains a difficult target due to its stroma-rich microenvironment and lack of high-density, tumor-specific antigens. This article emphasizes the need for tailor-made ADC designs to enhance results in various types of cancers and provides valuable insight into future advancements in precision oncology."

Journal • Review • Breast Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • Triple Negative Breast Cancer • MSLN • MUC1

Real World-clinical Outcomes of Tucatinib, Trastuzumab, and Capecitabine Following Trastuzumab Deruxtecan (T-DXd) for the Treatment of HER2-positive Metastatic Breast Cancer. (clinicaltrials.gov) - P=N/A | N=93 | Active, not recruiting | Sponsor: Pfizer | Not yet recruiting ➔ Active, not recruiting

Enrollment closed • Real-world evidence • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor

T-DXd effective as second-line therapy in G/GEJ cancers. (PubMed, Nat Rev Clin Oncol) - No abstract available

Journal • Gastric Cancer • Oncology

Comparative pharmacological analysis of fam-trastuzumab deruxtecan-nxki and sacituzumab govitecan-hziy: Two recently developed chemotherapies in the crucial battle against breast cancer. (PubMed, Toxicol Rep) - "While both therapies demonstrate therapeutic promise, continuous safety monitoring is essential. The FAERS dataset's demographic limitations highlight the need for more comprehensive post-marketing surveillance to assess long-term AE risks and optimize BC treatment safety."

Journal • Breast Cancer • Cardiovascular • Infectious Disease • Musculoskeletal Diseases • Oncology • Solid Tumor

Testing the Combination of DS-8201a and Olaparib in HER2-Expressing Cancers With Expansion in Patients With Platinum Resistant Ovarian Cancer (clinicaltrials.gov) - P1 | N=55 | Recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Jun 2025 ➔ Dec 2026 | Trial primary completion date: Jun 2025 ➔ Dec 2026

Platinum resistant • Trial completion date • Trial primary completion date • High Grade Serous Ovarian Cancer • Oncology • Ovarian Cancer • Solid Tumor • CD4

Reply to Letter to the Editor: 'A pooled analysis of trastuzumab deruxtecan in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer with brain metastases' by Y. Liu & C. Zhang. (PubMed, Ann Oncol) - No abstract available

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

A Study of Subcutaneous Trastuzumab Deruxtecan in Participants With Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=76 | Not yet recruiting | Sponsor: Daiichi Sankyo

New P1 trial • Solid Tumor

Sotorasib in Combination With Trastuzumab Deruxtecan for the Treatment of Locally Advanced and Metastatic Non-small Cell Lung Cancer With a KRAS G12C Mutation (clinicaltrials.gov) - P1/2 | N=37 | Not yet recruiting | Sponsor: National Cancer Institute (NCI)

New P1/2 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ERBB3 • KRAS

Case report: a R0 resection successfully induced by T-DXd plus PD-1 inhibitor regimen in a primary unresectable stage IIIB NSCLC with ERBB2-mutation. (PubMed, NPJ Precis Oncol) - "The patient remained recurrence-free at a 9-month follow-up. This induction targeted-IO strategy enabled surgical conversion in ERBB2-mutant NSCLC with durable remission and acceptable toxicity, warranting investigation in molecular subgroups with limited CRT-IO benefit."

IO biomarker • Journal • Interstitial Lung Disease • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pulmonary Disease • Respiratory Diseases • Solid Tumor • HER-2 • PD-L1

Prevalence of histology-agnostic biomarkers in pure squamous cell carcinomas of the genitourinary tract. (ASCO 2025) - "There are 8 FDA-approved histology-agnostic treatments based on biomarker profiling: dostarlimab (dMMR/MSI-H), pembrolizumab (dMMR/MSI-H; TMB-H), larotrectinib (NTRK fusion), entrectinib (NTRK fusion), selpercatinib (RET fusion), trastuzumab deruxtecan (HER2 positive), and dabrafenib plus trametinib (BRAF V600E mutation). This study provides a comprehensive analysis of the genetic landscape of pure SCC of the GU tract that may inform future therapeutic strategies for this rare tumor with limited treatment options. Almost one-third of patients were TMB-High, reflecting a population that may benefit from immune checkpoint inhibitors monotherapy or combination strategies. Other histology-agnostic targets for current therapies were relatively infrequent."

Biomarker • IO biomarker • Tumor mutational burden • Bladder Cancer • Genito-urinary Cancer • Microsatellite Instability • Oncology • Squamous Cell Carcinoma • Urothelial Cancer • BAP1 • BRAF • BRCA1 • BRCA2 • BRIP1 • CDKN2A • CHEK2 • FAT1 • FGFR3 • HER-2 • KDM6A • MSI • NTRK • PALB2 • PIK3CA • PTEN • RAD51 • RET • TERT • TMB • TP53

DESTINY-Lung04: A Study to Investigate the Efficacy and Safety of Trastuzumab Deruxtecan as the First Treatment Option for Unresectable, Locally Advanced/Metastatic Non-Small Cell Lung Cancer With HER2 Mutations (clinicaltrials.gov) - P3 | N=450 | Recruiting | Sponsor: AstraZeneca | Trial completion date: Mar 2027 ➔ Jul 2027 | Trial primary completion date: Jun 2025 ➔ Mar 2026

Trial completion date • Trial primary completion date • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • HER-2

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

Real-world use of antibody drug conjugates (ADCs) in metastatic bladder cancer: Analysis of 10,204 patients treated in clinical practice. (ASCO 2025) - "Enfortumab vedotin (EV) and Sacituzumab Govitecan (SG) are approved by regulatory agencies worldwide, and several other compounds are being investigated in clinical trials...Of all patients, only 922 (9%) were treated with any ADCs as a current or prior line of treatment, including EV, SG, Disitamab Vedotin, Tisotumab Vedotin, and Trastuzumab Deruxtecan... ADCs represent a new therapeutic option for the treatment of mBC, but our data suggest limited access worldwide despite regulatory approvals and clinical guideline recommendations. There is a geographic variation in the percentage of patients treated with ADCs, suggesting higher access in the US. Potential reasons include drug cost limiting access and approval delays in different regions."

Clinical • Metastases • Real-world • Real-world evidence • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • NECTIN4