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

Cancer Molecular Screening and Therapeutics (MoST) Program Substudy Addendum 8 substudy 19: T-DM1 (ANZCTR) - P2 | N=64 | Completed | Sponsor: The University of Sydney | Active, not recruiting ➔ Completed

Trial completion • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology

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 • Oncology • Solid Tumor

Effects of concurrent HER2-directed therapy on development of cerebral radionecrosis after stereotactic radiotherapy: a systematic review. (PubMed, Strahlenther Onkol) - "While concurrent use of T‑DM1/ADCs seems associated to elevated radionecrosis risk, an ambiguous situation for other substances persists. Heterogenous study designs with varying substances, definitions of concurrent use, and radionecrosis parameters must be considered. Included studies are partly limited by sample size and retrospective study design. Therefore, clinical implications remain difficult to claim; further research on this topic is needed."

Journal • Review • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • EGFR

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

A Randomized Phase 2 Study of Neratinib With or Without Fulvestrant for Patients With HER2-Positive, Estrogen Receptor-Positive Metastatic Breast Cancer. (PubMed, Clin Breast Cancer) - "The combination of neratinib and fulvestrant is safe and tolerable. Due to early study closure, this study was underpowered to detect the benefit of adding fulvestrant to neratinib. Chemotherapy-free regimens targeting ER and HER2 warrant further investigation, along with prospective studies investigating ctDNA dynamics may guide treatment switch."

Journal • P2 data • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2

Treatment of breast cancer in a patient with sickle cell disease. (PubMed, BMJ Case Rep) - "She received postmastectomy radiation followed by adjuvant trastuzumab emtansine...Throughout treatment, her SCD remained well-controlled, highlighting the potential for effective and tolerable cancer therapy in patients with SCD and the importance of interdisciplinary collaboration. This case underscores the importance of tailored oncological management and the need for further research on chemotherapy safety in this population."

Journal • Breast Cancer • Genetic Disorders • Hematological Disorders • Oncology • Sickle Cell Disease • Solid Tumor • ER • HER-2

Clinical Trial of TQB2102 for Injection Versus Trastuzumab Emtansine for Injection in HER2-positive Advanced Breast Cancer (clinicaltrials.gov) - P3 | N=246 | Not yet recruiting | Sponsor: Chia Tai Tianqing Pharmaceutical Group Nanjing Shunxin Pharmaceutical Co., Ltd.

New P3 trial • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor

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

ATEMPT 2.0: Adjuvant T-DM1 vs TH (clinicaltrials.gov) - P2 | N=500 | Recruiting | Sponsor: Dana-Farber Cancer Institute | Trial primary completion date: May 2025 ➔ Nov 2026

Trial primary completion date • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • HER-2

Adverse effect of trastuzumab deruxtecan in solid tumours: a systematic review and meta-analysis. (PubMed, Crit Rev Oncol Hematol) - "T-DXd has a safety and tolerability profile less favourable than classical chemotherapy. Dose, ethnicity and cancer site are associated with worse safety and tolerability."

Adverse events • Journal • Retrospective data • Review • Cardiovascular • Fatigue • Febrile Neutropenia • Hematological Disorders • Interstitial Lung Disease • Neutropenia • Oncology • Pulmonary Disease • Respiratory Diseases • Solid Tumor • Thrombocytopenia

Comparisons of survival outcomes of antibody-drug-conjugates in metastatic breast cancer: A network meta-analysis. (ASCO 2025) - " A total of 6449 patients from 12 RCTs of ADCs ado-trastuzumab emtansine (T-DM1), sacituzumab govitecan (SG), trastuzumab deruxtecan (T-DXd), and datopotamab deruxtecan (Dato-DXd) were included in the analysis. This network meta-analysis showed prominent survival benefits with ADC-containing regimens for mBC. Our results provide valuable insights into personalized treatment strategies for mBC patients."

Metastases • Retrospective data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor

Treatment-related toxicities of antibody-drug conjugates in breast cancer: A Bayesian network meta-analysis. (ASCO 2025) - " A total of 9307 patients in 17 RCTs of five different ADCs (ado-trastuzumab emtansine [T-DM1], sacituzumab govitecan [SG], trastuzumab deruxtecan [T-DXd], datopotamab deruxtecan [Dato-DXd], and ARX788) were included. This Bayesian network meta-analysis highlights significant variability in TRAEs among different ADCs in breast cancer therapy. T-DM1 was primarily associated with thrombocytopenia and hepatic toxicities, while SG and T-DXd were associated with neutropenia, anemia, GI disorders, and dermatological TRAEs. Our findings may help with selection of ADC therapies for patients with breast cancer, facilitating personalized approaches to minimize treatment-related toxicities."

Retrospective data • Alopecia • Anemia • Breast Cancer • CNS Disorders • Dermatology • Fatigue • Gastrointestinal Disorder • HER2 Breast Cancer • HER2 Positive Breast Cancer • Immunology • Musculoskeletal Diseases • Neutropenia • Oncology • Pruritus • Solid Tumor • Thrombocytopenia

First in human PK analysis of antibody conjugated liposome encapsulating doxorubicin (HF-K1) in advanced cancer patients: Comparison with ADCs. (ASCO 2025) - P1 | "Funded by Hangzhou Highfield Biopharmaceuticals Clinical Trial Registration Number: NCT05861895 Background: Antibody drug conjugates (ADCs) have been shown to have a better therapeutic index however there have been reports of serious toxicity limiting their use. Based on the analysis, we identified that with similar endocytosis rates, the greater DAR could lead to higher intracellular drug uptake with HF-K1 as compared to DS8201a and T-DM1. We therefore anticipate better clinical efficacy with HF-K1. HF-K1 is currently being evaluated in an ongoing study (NCT05861895) in patients with advanced solid tumors with HER2 expression (IHC 1+, 2+, 3+)."

Clinical • Metastases • P1 data • Oncology • Solid Tumor • HER-2

Real-world treatment patterns and outcomes in HER2-positive metastatic breast cancer patients with brain metastases. (ASCO 2025) - "First line systemic therapy for HER2+ MBC is trastuzumab (H), pertuzumab (P) and Taxol (T). Subsequent therapies include trastuzumab emtansine (T-DM1), tucatinib/H/capecitabine triplet therapy (TUC) and trastuzumab deruxtecan (T-DXd)... TUC and T-DXd are increasingly prescribed as initial systemic treatment after BM diagnosis. The combination of SRS and HER2 targeted therapies in this cohort resulted in excellent survival outcomes with limited risk of RN. Future studies and longer follow-up will allow for a better understanding of how treatment patterns affect survival outcomes and patient quality of life."

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

Trastuzumab deruxtecan (T-DXd) in HER2-positive advanced breast cancer (ABC) with active CNS metastases: Real world data. (ASCO 2025) - "Median lines of previous treatment in ABC was four (0-11), the most pts have received pertuzumab (n = 61, 87%), 19 of them (31%) in neoadjuvant setting. With T-DM1 were treated 58 pts (83%), with lapatinib – 23 pts (33%); all 3 anti-HER2 Rx received 17 pts (24%)... In real clinical practice therapy with T-DXd is highly effective in patients with ABM, including those previously irradiated. The therapy was well tolerated, no new data on AEs were received."

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

Efficacy and safety of trastuzumab deruxtecan for metastatic HER2+ and HER2-low breast cancer: A systematic review and meta-analysis of randomised controlled trials. (ASCO 2025) - "T-DXd has proven to be highly effective for treating metastatic HER2-+ and HER2-low breast cancer, providing an important option for patients with advanced disease. However, treatment is associated with notable side effects. This highlights the importance of carefully selecting patients and closely monitoring them to manage potential risks."

Metastases • Retrospective data • Review • 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 | "TDM1 demonstrated efficacy in multiple HER2-amp tumor types. The highest ORR was seen in salivary gland tumors, with a median time on treatment of about 1.5 years. More work is needed to understand the enhanced efficacy of TDM1 in these tumors."

Clinical • P2 data • Pan tumor • Breast Cancer • Colorectal Cancer • Endometrial Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pneumonia • Salivary Gland Cancer • Solid Tumor • HER-2

Safety and efficacy of TQB2102, a novel bispecific anti-HER2 antibody–drug conjugate, in patients with advanced solid tumors: Preliminary data from the first-in-human phase 1 trial. (ASCO 2025) - P1, P3 | "The bispecific antibody component can target both extra-cellular domains II (pertuzumab binding site) and IV (trastuzumab binding site) of HER2...Most common tumor types included MBC (N = 80),Colorectal cancer(N = 37)and Gastric cancer (N = 23).Twenty-five (31%) MBC received prior anti-HER2 ADCs, including 21 pts received T-DM1, 8 pts received DS-8201.The median duration of follow-up was 8.15 months... TQB2102 is well tolerated with promising anti-tumor activity in pts with HER2-expressing cancer. These early signs of activity support a phase 3 trial in patients with HER2-low MBC that has been initiated (NCT06561607)."

Clinical • Metastases • P1 data • Anemia • Breast Cancer • Colorectal Cancer • Gastric Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Interstitial Lung Disease • Oncology • Pulmonary Disease • Respiratory Diseases • Solid Tumor

Efficacy of systemic therapy in breast cancer with CNS metastases: "Real-world" experience. (ASCO 2025) - "Tucatinib-based regimens showed a 100% DCR with median PFS of six months. Other therapies, including sacituzumab, abemaciclib, and trastuzumab-emtansine, showed stable disease as the best response... This "real-world" experience highlights that, at our institution, most patients with breast cancer and CNS metastases considered for upfront systemic therapy lack measurable disease (91% having lesions < 10 mm) typically required for clinical trials. Nonetheless, the response rate aligns with published experiences. In addition, we included patients with LMD, who are often excluded in trials."

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

Racial and ethnic disparities in clinical outcomes of HER2-positive metastatic breast cancer treated with antibody-drug conjugates: A TriNetX real-world evidence study. (ASCO 2025) - "Antibody drug conjugates (ADCs), such as trastuzumab deruxtecan (T-DXd) and ado-trastuzumab emtansine (T-DM1), both approved for metastatic HER2+ BC, have significantly improved survival in this population. Our study shows better outcomes with use of ADCs in heavily pretreated metastatic HER2-BC, with 83.7% of patients surviving beyond 5 years. However, significant racial disparities were observed, with Asian patients showing the highest survival while Black patients had the poorest survival which could be due to multi-level factors. Future studies are needed to understand the underlying mechanisms behind this racial disparity in outcomes with HER2-directed ADCs to inform strategies to improve patient outcomes."

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

Risk of radiation necrosis with concurrent antibody-drug conjugates and radiotherapy in HER2-positive breast cancer with brain metastases: A meta-analysis. (ASCO 2025) - "Funded by No funding sources reported Background: Antibody-drug conjugates (ADCs) have transformed the outcomes of HER2-positive breast cancer (BC), particularly in patients with brain metastases (BM) due to the use of ADCs like trastuzumab emtansine (T-DM1) and trastuzumab deruxtecan (T-DXd), which have demonstrated intracranial efficacy. C-ADC is associated with a significantly higher risk of SRN. This risk is concerning but must be balanced against potential improvements in local control and efficacy outcomes. Prospective studies are needed to optimize treatment schedule and sequences to minimize toxicity and optimize survival."

Retrospective data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • 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) - "This real-world analysis provides insight into baseline GAs and associations with TTNT on T-DXd, T-DM1 and SG in MBC as well as GAs that emerge on treatment. ERBB2amp by CGP carried additional predictive value to IHC/FISH HER2 status in both HER2+ and HER2-low MBC treated with T-DXd and HER2+ MBC treated with T-DM1."

Metastases • Breast Cancer • Oncology • Solid Tumor • BRCA1 • BRCA2 • EGFR • ERCC4 • GNAS • HER-2 • PIK3CA • TP53

Transcriptomic biomarkers of therapeutic response to antibody-drug conjugates in metastatic breast cancer: A comprehensive multi-center study. (ASCO 2025) - "Funded by Tempus AI, Inc Background: The three antibody-drug conjugates (ADCs) — sacituzumab govitecan (SG), trastuzumab deruxtecan (T-DXd), and trastuzumab emtansine (T-DM1) — that are FDA-approved for treatment of metastatic breast cancer (MBC) have markedly improved patient outcomes. Multi-modal analysis identified drug efflux pump gene expression as a potential biomarker of resistance, primarily to T-DXd. These findings should be further validated, and combinatorial clinical trial strategies may be explored."

Biomarker • Clinical • Metastases • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ABCB1 • ABCC1 • ABCC4 • ABCG2 • HER-2

Efficacy and safety results of TQB2930, a HER2-targeted bispecific antibody combined with chemotherapy in patients with HER2-positive breast cancer (BC) previously treated with ≥2 line treatments: Results from a phase 1b/2 study. (ASCO 2025) - P1/2 | "All enrolled patients received TQB2930 intravenously at a dose of 30 mg/kg every three weeks (Q3W), administered in combination with one of four investigator-selected chemotherapies (capecitabine, eribulin, gemcitabine, or vinorelbine)...Among patients who had progressed on prior T-DM1 therapy, the ORR was 36.8% (7/19), whereas patients who had failed other HER2-ADC therapies exhibited an ORR of 50% (8/16), including RC48, DS-8201, and so on... The combination of TQB2930 with chemotherapy demonstrates encouraging antitumor efficacy and an acceptable safety profile in patients with HER2-positive BC who have undergone at least two prior lines of treatment. These results support the potential of TQB2930 as a novel therapeutic strategy for HER2-positive BC and underscore the need for further clinical exploration. This study was funded by Chia Tai Tianqing Pharmaceutical Group Nanjing Shunxin Pharmaceutical Co., Ltd."

Clinical • P1/2 data • Breast Cancer • Cardiovascular • HER2 Breast Cancer • HER2 Positive Breast Cancer • Neutropenia • Oncology • Solid Tumor • Thrombocytopenia • CD4 • HER-2

Efficacy of tucatinib, trastuzumab, and capecitabine (TTC) following trastuzumab-deruxtecan (T-DXd) in HER2-positive metastatic breast cancer (MBC): Updated results and subgroup analyses from the UNICANCER multicenter retrospective cohort. (ASCO 2025) - "Patients had received a median of 4 prior MBC therapies (range: 2–15), which included pertuzumab (81%) and T-DM1 (93%). This large retrospective cohort with extended follow-up highlights the efficacy of TTC in HER2-positive MBC patients previously treated with T-DXd. These findings support the role of TTC as a viable treatment option post-T-DXd and provide insights for optimizing therapeutic strategies in this setting."

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