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

Perivascular Niche-Resident Alveolar Macrophages Promote Interstitial Pneumonitis Related to Trastuzumab Deruxtecan Treatment. (PubMed, Cancer Res) - "These findings elucidate a mechanism by which T-DXd ignites the lung immune microenvironment and underscore the importance of off-target endocytosis by innate immune cells in the development of ADC-related toxicities. Significance: Preconditioning the perivascular niche can prevent lung inflammation induced by antibody-drug conjugate phagocytosis by alveolar macrophages and subsequent SPP1high macrophage differentiation, providing a clinically viable strategy for mitigating interstitial lung disease."

Journal • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Inflammation • Interstitial Lung Disease • Oncology • Pneumonia • Pulmonary Disease • Respiratory Diseases • Solid Tumor • SPP1

BAY 2927088: a novel treatment option for patients with NSCLC with HER2 mutations (AACR 2025) - P1/2, P3 | "About 2-4% of patients with non-small cell lung cancer (NSCLC) carry either a HER2 exon20 insertion or a HER2 point mutation, which are potent oncogenic drivers.The antibody-drug conjugate fam-trastuzumab deruxtecan-nxki was the first targeted treatment option to be approved for patients with HER2-mutant NSCLC. We found that BAY 2927088 was also active in a subset of HER2-amplified breast and gastroesophageal cancer cell lines.Single-agent BAY 2927088 is currently being evaluated in clinical trials in patients with NSCLC with HER2 mutations. Preliminary results demonstrate efficacy and safety in pretreated patients (NCT05099172, NCT06452277)."

Clinical • Esophageal Cancer • Gastric Cancer • Gastroesophageal Cancer • HER2 Positive Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • HER-2

Impact of early tumor shrinkage on survival outcomes in patients with HER2-positive advanced gastric cancer treated with trastuzumab deruxtecan in third- or later-line settings. (PubMed, Therap Adv Gastroenterol) - "T-DXd demonstrated notable efficacy and a manageable safety profile in patients with HER2-positive AGC. Rapid and deep tumor shrinkage may have a significant impact on survival."

Journal • Gastric Cancer • Oncology • Solid Tumor • HER-2

The mechanisms of HER2 targeted ADCs are dependent on Rab GTPases. (PubMed, Ther Adv Med Oncol) - "This study aimed to compare trastuzumab deruxtecan (T-DXd) to ado-trastuzumab emtansine (T-DM1) with emphasis on Rab GTPase-regulated intracellular trafficking and its impact on ADC efficacy. The study demonstrates that ADC design significantly influences intracellular trafficking and processing. The linker design, in particular, plays a major role in determining the intracellular fate of an ADC."

Journal • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2 • RAB5A

A Meta-Analysis Studying the Difference in Response to Trastuzumab-Deruxtecan Based on HER2 Immunohistochemistry Staining in HER2 Low Metastatic Breast Cancer Patients. (PubMed, Am J Ther) - No abstract available

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

A Review of NICE UK Submissions for Antibody-Drug Conjugates in Oncology (ISPOR 2025) - "All of these ADCs were assessed by NICE from inception to 2024 12 FDA-approved ADCs were identified: Trastuzumab emtansine, Trastuzumab deruxtecan, Sacituzumab govitecan, Inotuzumab ozogamicin, Polatuzumab vedotin, Loncastuximab tesirine, Tisotumab vedotin, Enfortumab vedotin, Mirvetuximab soravtansine-gynx, Belantamab mafodotin-blmf, Gemtuzumab ozogamicin, and Brentuximab vedotin. In conclusion, ADCs have revolutionized cancer treatment with their targeted delivery and significant therapeutic benefits. The evolution of ADCs since 2000 highlights their potential in both refractory and early-stage diseases. Continued advancements in ADC design and technology promise even greater therapeutic efficacy."

NICE • Review • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • B Cell Lymphoma • Breast Cancer • Cervical Cancer • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • Ovarian Cancer • Solid Tumor • Urothelial Cancer

Real-World Evaluation of Trastuzumab Deruxtecan Administration, Compliance, and Dose Utilization in Chinese Patients With HER2-Positive Advanced Breast Cancer (ISPOR 2025) - "Treatment compliance was acceptable (more than 6 cycles). However, the administered dose was lower than recommended, and treatment intervals were longer than the recommended 21 days. A small percentage of patients received standard treatment."

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

Summary of Evolving Role and Impact of Real World Evidence (RWE) in US FDA Regulatory Approvals (2020-2024) (ISPOR 2025) - "Notable cases like Rozlytrek (entrectinib) for rare cancers leveraged synthetic control arms, Zolgensma (onasemnogene abeparvovec-xioi) used RWE for expanded indications...Examples include Enhertu (fam-trastuzumab deruxtecan-nxki) for HER2-low breast cancer and Evrysdi (risdiplam) for spinal muscular atrophy, supported by longitudinal real-world data. 1) 2020, RWE was primarily used in label expansions and post-marketing safety evaluations, particularly in oncology and rare diseases. Notable approvals included Ibrance (palbociclib) for male breast cancer, based on real-world data from EHRs.2) 2021, during COVID-19 pandemic, RWE played a key role in Emergency Use Authorizations (EUAs) and full approvals of treatments like Veklury (remdesivir). The % of approvals involving RWE increased to 15-20%, with RWE supporting label expansions for drugs like Keytruda (pembrolizumab).3)2022, RWE contributed to 25-30% of approvals, including initial NDAs and BLAs."

Clinical • HEOR • Real-world • Real-world evidence • Alzheimer's Disease • Breast Cancer • CNS Disorders • Genetic Disorders • HER2 Breast Cancer • HER2 Positive Breast Cancer • Infectious Disease • Male Breast Cancer • Movement Disorders • Muscular Atrophy • Novel Coronavirus Disease • Oncology • Rare Diseases • Solid Tumor • HER-2

Role of External Control Arm (ECA) Derived from Real World Data (RWD) in US FDA Regulatory Approval from 2020-2024 (ISPOR 2025) - "OBJECTIVES: To analyze role of ECA in US FDA approvals ( 2020 - 2024) & summarize the key disease areas leveraging ECA. systematic literature review and analysis of all novel drug approvals including NDA (New Drug Application) and BLA (Biological License Application)submitted from 2020-2024 were analyzed. The percentage of approvals involving external control arms increased steadily, particularly in rare diseases, oncology, and conditions with small or hard-to-recruit patient populations from 2020-2024 2020: Early Exploration (5-7% of Approvals) : 1.Ibrance (palbociclib): Used retrospective RWD to support male breast cancer indication...Blincyto (blinatumomab): Supplemental approvals for rare cancers based on external data. 2021: Accelerated Adoption Amid COVID-19 (10-15% of Approvals) 1.Veklury (remdesivir): Approval supported by real-world hospital data as external comparisons...Keytruda (pembrolizumab): Label expansion for certain cancers using external control..."

Clinical • Real-world • Real-world evidence • Alzheimer's Disease • Breast Cancer • CNS Disorders • Genetic Disorders • HER2 Breast Cancer • HER2 Positive Breast Cancer • Infectious Disease • Male Breast Cancer • Movement Disorders • Muscular Atrophy • Novel Coronavirus Disease • Oncology • Rare Diseases • Solid Tumor • HER-2

Use of Patient Support Program Data for Real-World Evidence Generation: Opportunities and Pitfalls Illustrated in a Case Study Assessing Trastuzumab Deruxtecan Among Patients With Breast Cancer (ISPOR 2025) - P | "RWE using PSP data offers unique opportunities to enhance decision making and improve patient outcomes. However, RWE leveraging the PSP should be planned early, ensure transparency/methodological rigor, and outline all known limitations."

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

Socioeconomic Value of Targeted Therapies for HER2+ Breast Cancer in National Reimbursement Drug List of China (ISPOR 2025) - "However, few researches quantified the socioeconomic value of innovative medications in China. Socioeconomic values of 7 targeted therapies in National Reimbursement Drug list (NRDL) from 2023 to 2032 were estimated, covering Trastuzumab, Pertuzumab, Ado-trastuzumab Emtansine, pertuzumab+trastuzumab+hyaluronidase-zzxf (Subcutaneous Injection), Neratinib, Pyrotinib and Fam-trastuzumab Deruxtecan. Targeted therapies for HER2+ in breast cancer significantly improve patients' quality of life and create great socioeconomic values. It implies that NRDL inclusion of these innovative medication not only provides reimbursement but also yields great socioeconomic impacts in China."

Reimbursement • US reimbursement • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Clinical implications of peripheral blood biomarkers in patients with advanced breast cancer treated with trastuzumab emtansine and trastuzumab deruxtecan. (PubMed, Int J Clin Oncol) - "Immune status may influence treatment outcomes in the T-DM1 and T-DXd (HER2-low) groups. Conversely, in the T-DXd (HER2-positive) group, the treatment outcome was independent of immune status."

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

Enhertu: Regulatory decision in China for HER2 low breast cancer ((based on DESTINY BREAST06 trial) in 2026 (AstraZeneca) - Q1 2025 Results

China approval • Breast Cancer • Oncology

Enhertu: Data from P3 DESTINY-Lung04 trial (NCT05048797) for HER2-mutated, unresectable, locally advanced/metastatic NSCLC in 2026 (AstraZeneca) - Q1 2025 Results

P3 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology

Enhertu: Data from monotherapy arm of P3 DESTINY-Breast09 trial (NCT04784715) for HER2-positive,1L advanced or metastatic breast cancer in 2026 (AstraZeneca) - Q1 2025 Results: Data from P1b/2 DESTINY-Breast07 trial (NCT04538742) for HER2-positive metastatic breast cancer in H2 2025

P1/2 data • P3 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology

A multicenter randomized open-label phase 2 study investigating optimal antiemetic therapy for patients with advanced/recurrent gastric cancer treated with trastuzumab deruxtecan: the EN-hance study. (PubMed, Int J Clin Oncol) - "Given that the primary endpoint was not met, further research is needed to better characterize nausea and vomiting with T-DXd to tailor an anti-emetic regimen that suits the needs of the patients."

Journal • P2 data • Gastric Cancer • Oncology • Solid Tumor • HER-2

HUDSON: Phase II Umbrella Study of Novel Anti-cancer Agents in Patients With NSCLC Who Progressed on an Anti-PD-1/PD-L1 Containing Therapy (clinicaltrials.gov) - P2 | N=527 | Active, not recruiting | Sponsor: AstraZeneca | Trial primary completion date: Sep 2026 ➔ Sep 2024

Biomarker • IO biomarker • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

PONTIAC: Safety and Efficacy of T-DXd vs. CDK4/6i-based ET as First-line Therapy of HR-positive and HER2-low/Ultralow Advanced Breast Cancer Patients Classified as Non-luminal Subtype (clinicaltrials.gov) - P2 | N=200 | Not yet recruiting | Sponsor: MedSIR | Initiation date: Dec 2024 ➔ May 2025

Trial initiation date • Breast Cancer • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor

Metabolic Reprogramming Enhances HER2-CAR T Cell Therapy for HER2-ADC-resistant tumors (ASGCT 2025) - "Background: HER2-ADC therapy (e.g., T-DXd) has limited success in HER2-positive tumors, with a response rate of just 29.4% in solid tumors... Metabolic reprogramming via ADA1 and CD26 transforms HER2-CAR T cells into a potent therapy for HER2-ADC-resistant tumors. This approach enhances metabolic fitness, persistence, and antitumor efficacy, offering a promising strategy to overcome current therapeutic limitations. Further clinical validation is warranted."

CAR T-Cell Therapy • Oncology • Solid Tumor • DPP4 • EGFR • ERBB3

Real-time, Label-free Assessment of HER2-targeted Antibody-drug Conjugate Therapies (ASGCT 2025) - "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. Disease Focus of Abstract:Cancer Solid Tumors"

Oncology • Solid Tumor • HER-2

FT836, a Novel MICA/B-targeting CAR T-cell Therapy Engineered to Eliminate the Need for Conditioning Chemotherapy with Broad Activity Across Solid Tumor Indications (ASGCT 2025) - "Notably, combination with chemotherapy, radiotherapy, or antibody drug conjugates, such as trastuzumab-deruxtecan, increased MICA/B expression on tumor cells and enhanced FT836 CAR-mediated anti-tumor activity. As a result, FT836 is uniquely equipped to eliminate the need for conditioning chemotherapy, facilitating broader clinical application both as monotherapy and in combination with standard-of-care agents such as chemotherapy and therapeutic monoclonal antibodies, overcoming multiple challenges that limit adoptive cell therapies in treating solid tumor. Disease Focus of Abstract:Cancer Solid Tumors"

CAR T-Cell Therapy • IO biomarker • Cervical Cancer • Infectious Disease • Oncology • Solid Tumor • CD58 • EGFR • MICA • MICB • NKG2D

[Ad hoc announcement pursuant to Art. 53 LR] Roche continues good momentum into 2025 with 6% (CER) sales growth in the first quarter (Roche Press Release) - "Strong demand for both pharmaceutical products and diagnostic solutions more than made up for the impact from the loss of exclusivity on Avastin (various types of cancer), Herceptin (breast and gastric cancer), MabThera/Rituxan (blood cancer, rheumatoid arthritis), Esbriet (lung disease), Lucentis (severe eye diseases) and Actemra/RoActemra (rheumatoid arthritis, COVID-19), totalling CHF 0.2 billion, and the impact of the recent healthcare pricing reforms in China...The top five growth drivers – Phesgo, Vabysmo, Xolair, Hemlibra and Xofluza (influenza) – achieved total sales of CHF 3.6 billion; Sales in Europe grew by 5% as the strong uptake of Vabysmo, Polivy, Ocrevus, Phesgo and Hemlibra; In Japan, sales increased by 3% due to growth in sales of Phesgo, Vabysmo...Diagnostics: key developments - Roche receives FDA approval for the first companion diagnostic to identify patients with HER2-ultralow metastatic breast cancer eligible for ENHERTU"

Commercial • Ankylosing Spondylitis • Asthma • HER2 Breast Cancer • Non Small Cell Lung Cancer • Non-Hodgkin’s Lymphoma • Ophthalmology • Ovarian Cancer • Pruritus • Schizophrenia

Body composition metrics as a determinant of trastuzumab deruxtecan related toxicity and response. (PubMed, NPJ Breast Cancer) - "A body mass index over 25 kg/m2 was linked to higher dose reductions (OR = 4.97, p = 0.016). These findings emphasize the need for personalized treatment strategies based on body composition."

Journal • Breast Cancer • Obesity • Oncology • Solid Tumor

Comparison of Clinicopathological Characteristics for HER2-Null, HER2-Ultralow and HER2-Low Breast Cancer: A Single-Center Study. (PubMed, Medicina (Kaunas)) - "Background and Objectives: A recent clinical trial has demonstrated that breast cancer with low-HER2 expression levels responds to trastuzumab deruxtecan treatment...HER2-low tumors tend to recur much more frequently and with poorer outcomes. In this field, new therapeutic approaches may result in better outcomes."

Clinical • Journal • Retrospective data • Breast Cancer • 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

HER2-Low Breast Cancer-Current Knowledge and Future Directions. (PubMed, Medicina (Kaunas)) - "Differences exist between this group and HER2-null breast cancer. In this review, we provide an update on HER2-low and HER2-ultralow breast cancer, including background trial data, the evolution of HER2-low expression, current clinical guidelines, quality issues, and future directions."

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