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

Utility of HER2 mRNA expression to predict HER2 IHC positivity in advanced solid tumors (HOPA 2026) - "Background: The tumor-agnostic approval of trastuzumab deruxtecan suggests that HER2 immunohistochemistry (IHC) testing should be considered more broadly, despite low levels of positivity in some tumor types... HER2 mRNA overexpression demonstrated limited predictive value as a single indicator of IHC 3+ status in our small cohort. Neither mRNA nor DNA-based metrics appear reliable on their own and should be interpreted in conjunction with IHC staining. We observed limited use of HER2 IHC testing in solid tumors, suggesting the need for increased awareness of HER2 biomarker testing for tumor agnostic use of HER2-directed therapies."

Metastases • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • HER-2

Retrospective Analysis of Interstitial Lung Disease in Patients Receiving Fam-Trastuzumab Deruxtecan at Avera Health: Incidence, Risk Factors, and Management Strategies (HOPA 2026) - "Results pending at time of abstract submission"

Retrospective data • Breast Cancer • Interstitial Lung Disease • Pneumonia • Pulmonary Disease • Respiratory Diseases • Solid Tumor

Evaluation of Interstitial Lung Disease Associated with Trastuzumab Deruxtecan in Gynecologic Malignancies (HOPA 2026) - "Conclusion is currently pending."

Gynecologic Cancers • Interstitial Lung Disease • Oncology • Pulmonary Disease • Respiratory Diseases • Solid Tumor • HER-2

310: Beyond EGFR and ALK: Updates in Biomarker-Driven Treatments in NSCLC (HOPA 2026) - "Emerging data on HER2-targeted therapies, trastuzumab deruxtecan, zongertinib, and sevabertinib in HER2 mutant NSCLC will also be reviewed, with emphasis on clinical efficacy, safety, and treatment sequencing. UAN: 0465-0000-26-058-L01-P Knowledge or Application Based: Application Learning Objectives: Describe the role of taletrectinib in the treatment of ROS1-rearranged NSCLCApply recently approved zenocutuzumab in the treatment of NSCLC with NRG1 fusionIntegrate telisotuzumab vedotin into therapeutic decisions for NSCLC patients with c-MET overexpressionReview clinical data evaluating the use of trastuzumab deruxtecan, zongertinib and sevabertinib in the treatment of HER2-mutation-positive NSCLC"

Biomarker • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • ALK • EGFR • MET • NRG1 • ROS1

Real World Evaluation of Trastuzumab Deruxtecan Associated Toxicity in Patients with Renal and/or Hepatic Impairment (HOPA 2026) - "Conclusions pending finalized results."

Clinical • HEOR • Real-world • Real-world evidence • Breast Cancer • Hepatology • HER2 Breast Cancer • HER2 Positive Breast Cancer • Liver Failure • Pneumonia • Renal Disease • Solid Tumor • HER-2

North American Enrollment in Clinical Trials: An Emerging Issue for Regulatory Approval (HOPA 2026) - "In the Asian region, the median OS was not estimable for glofitamab plus gemcitabine and oxaliplatin versus 8.2 months in rituximab plus gemcitabine and oxaliplatin.1 In the rest of the world, the median OS was 21.2 months for glofitamab plus gemcitabine and oxaliplatin versus 27.8 months for rituximab plus gemcitabine and oxaliplatin.1 Even when excluding the OS data, which could be confounded by subsequent therapy, the pooled non-Asian patient data (ie, in United States, Europe, Australia) found glofitamab plus gemcitabine and oxaliplatin did not have significantly longer PFS than with rituximab plus gemcitabine and oxaliplatin.1 The Asian population had more lenalidomide exposure and only 2 of the 131 patients previously received CAR T therapy compared with 19 of 143 patients from the rest of the world.1 In the United States, CAR T therapy is standard of care second- or third-line therapy, whereas there is limited or no access to CAR T therapy in Asia3 Was this an..."

Clinical • B Cell Lymphoma • Breast Cancer • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Genito-urinary Cancer • Hematological Malignancies • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Negative Breast Cancer • Leukemia • Lung Cancer • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Prostate Cancer • Small Cell Lung Cancer • Solid Tumor • HER-2

302: Navigating the Gray: Evidence and Art of Adverse Effect Management in Breast Cancer (HOPA 2026) - "Presented as 4 patient cases, this presentation will gauge the audience's clinical practice followed by a review of current evidence and integration of the patient's perspective on toxicities and strategies to manage adverse effects. UAN: 0465-0000-26-056-L01-P Knowledge or Application Based: Application Learning Objectives: Create a monitoring and treatment plan for CDK4/6 inhibitor- induced hepatotoxicityDiscuss counseling points for stomatitis prevention and treatment with datopotamab deruxtecan Apply data to customize a treatment and supportive care plan for interstitial lung disease from trastuzumab deruxtecan Summarize the monitoring and treatment of hyperglycemia associated with PI3K inhibitors Understand financial and time toxicities of supportive care management of breast cancer patients"

Adverse events • Breast Cancer • Dental Disorders • Diabetes • Interstitial Lung Disease • Oncology • Pulmonary Disease • Respiratory Diseases • Solid Tumor • Stomatitis

A Trial of Trastuzumab Rezetecan in Unresectable Locally Recurrent/Metastatic Breast Cancer (clinicaltrials.gov) - P2 | N=150 | Not yet recruiting | Sponsor: Jiangsu HengRui Medicine Co., Ltd.

New P2 trial • Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor

Modeling of de novo and experimentally induced acquired resistance to trastuzumab deruxtecan in HER2-positive patient-derived xenografts (AACR 2026) - "They enable the direct comparison of molecular mechanisms driving both intrinsic and treatment-induced resistance in a controlled, in vivo setting. This platform is immediately applicable for investigating alterations in HER2 biology, payload delivery, and bypass signaling pathways, and is ideally suited for evaluating novel therapeutic strategies aimed at overcoming T-DXd resistance."

Clinical • Preclinical • Oncology • HER-2

Development of enhanced enhertu-resistant HER2-positive breast cancer models for ADC resistance research (AACR 2026) - "Together, these Enhertu-resistant models offer a practical system to investigate resistance mechanisms that may not yet be evident in clinical samples and to identify candidate biomarkers and therapeutic targets. These cell lines also enable preclinical testing of biomarker-guided combination therapies and next-generation ADCs designed to overcome Enhertu resistance in HER2-positive malignancies."

ADC • Preclinical • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • ABCG2 • HER-2

DESTINY-PanTumor02: A Phase 2 Study of T-DXd in Patients With Selected HER2 Expressing Tumors (clinicaltrials.gov) - P2 | N=477 | Active, not recruiting | Sponsor: AstraZeneca | Recruiting ➔ Active, not recruiting

Enrollment closed • Pan tumor • Biliary Tract Cancer • Bladder Cancer • Breast Cancer • Cervical Cancer • Endometrial Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Pancreatic Cancer • Solid Tumor

QLS1403, a novel and potent PARG inhibitor with robust anti-tumor efficacy in homologous recombination deficient cancer models (AACR 2026) - "IDE-161, a first-in-class PARG inhibitor has entered clinical trials. QLS1403 demonstrates superior potency, sustained efficacy in PARPi-resistant and T-Dxd-resistant cancer cell lines, while displaying favorable safety. These compelling data support its clinical evaluation as a new therapeutics for patients with HRD-positive cancers with acquisition of resistance to PARPi or potentially other existing treatments, such as T-Dxd."

Clinical • Preclinical • Breast Cancer • Oncology • Ovarian Cancer • Solid Tumor • HRD

Bi- and tri-specific ADCs that target two distinct growth factor receptor forms of MUC1* and HER2 or alpha-v-beta-6 inhibit tumor recurrence and overcome acquired resistance (AACR 2026) - "Indeed, in Phase I huMNC2-CAR44 trial, patients who had acquired resistance to Trastuzumab or Fam-Trastuzumab Deruxtecan-nxki were best responders in our trial with 75% DCR, 11-month OS, 11.3 month increased survival in patients with high MUC1* expression. It is critical that MUC1-targeted therapeutics hit the cancer-specific forms of MUC1*. Therapeutics that incorporate antibodies that bind to hematopoietic stem cells, for example, would be disastrous if given to cancer patients. Therapeutics that target full-length MUC1, whether aberrantly glycosylated or not, could give initial positive responses via ADC bystander killing."

ADC • Preclinical • Trispecific • Oncology • Solid Tumor • HER-2 • MUC1

Dual-payload antibody drug conjugate targeting TROP2: Multi-Payload Conjugates™ targeting orthogonal mechanisms of cell killing (AACR 2026) - "Sacituzumab govitecan (SG), is approved as a 3rd line therapy in metastatic HER2 negative breast cancer...In head-to-head comparisons, CATB-101 outperforms T-DXd, SG and Dato-DXd with full tumor elimination at low doses... Advances have been made in the design of ADCs to expand to previously unaddressed populations. High patient relapse and the failure of recent mono-payload ADCs in late-stage trials indicate a need for next generation multi-payload conjugates. Catena's MPCs™ offer a next step in ADC design and allow for targeted delivery of multiple mechanisms of action with a single MPC™ while reducing off-target toxicity."

ADC • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • EGFR • HER-2 • TACSTD2 • TOP1

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

An RNA-based survival model predicting real-world response to trastuzumab deruxtecan (AACR 2026) - "Top predictive features aligned with ADC biology, including TOP3B and TOP2A (topoisomerase payload), ATM and TP53 (DNA damage response), HIF1A (hypoxia), ESR1 (hormone signaling), and XBP1/NFATC1 (stress and immune regulation).This Enhertu survival model applies biologically structured AI to real-world RNA-seq data to reveal treatment-specific patterns of response. Integrating large-scale embeddings, mechanistic biomodules, and survival modeling, we identified biological programs related to DNA repair and stress response associated with T-DXd benefit."

Clinical • Real-world • Real-world evidence • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2 • HIF1A • NFATC1 • TOP2A • TOP3B • TP53 • XBP1

Integrative transcriptomic profiling reveals stromal activation patterns in gastric cancer beyond HER2 status (AACR 2026) - "Although recent clinical activity of trastuzumab deruxtecan has refined HER2 classification, biological determinants of treatment response in non-HER2-driven subtypes, especially GS-like disease, remain poorly understood...Stromal remodeling, represented by fibrosis and angiogenesis scores, is a major biological feature of AGC and is particularly enriched in GS-like tumors, independent of HER2 status. These findings suggest that fibrosis- and angiogenesis-based stromal programs may improve biological stratification and identify tumor-microenvironment-driven vulnerabilities in advanced gastric cancer."

IO biomarker • Stroma • Gastric Cancer • Oncology • Solid Tumor • HER-2 • KRAS • PD-L1

Plinabulin boosts antitumor efficacy of topoisomerase inhibitor-based antibody-drug conjugates without or with immune checkpoint inhibitor (AACR 2026) - "Preclinically, Plin boosts irinotecan activity in human colon cancer models and reduces topotecan-induced neutropenia. Here we investigated Plin synergy with TOP1-ADC in-vitro, and with or without PD-1/L1 inhibitor pembrolizumab (Pembro) or atezolizumab (Atezo) in-vivo. For combinations in-vitro, HER2+ KPL-4 breast cancer cells were treated with Plin (1.46 - 46.8 nM), T-DXd (0.105 - 3.37 μM) or both. For combinations in-vivo, MC38 mouse colon adenocarcinoma cells overexpressing hTROP2 (hTROP2-MC38) or hHER2 (hHER2-MC38), were inoculated in B-hPD-1 or B-hPD-1/hPD-L1/hHER2 mice respectively, and antitumor activities of Plin (7.5 mg/kg) plus Dato-DXd (5 mg/kg) ± Pembro (0.3 mg/kg) or T-DXd (3 mg/kg) ± Atezo (8 mg/kg) were evaluated. On HER2+ KPL-4 cells, Plin showed synergistic activity with T-DXd with median CI <1 at 1:1, 2:1 and 4:1 ratios (T-DXd:Plin)... Plinabulin is a Phase 3 novel agent clinically validated to promote DC maturation and T-cell activation,..."

ADC • Checkpoint inhibition • Clinical • Breast Cancer • Colon Adenocarcinoma • Colon Cancer • Colorectal Adenocarcinoma • Colorectal Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2 • PD-L1 • TACSTD2 • TOP1

Exatecan payload-based antibody-drug conjugates with a short hydrophilic beta-glucuronidase cleavable linker (AACR 2026) - "We synthesized an ADC comprising trastuzumab conjugated to an exatecan payload via this novel, short, stable, hydrophilic linker AV-L03 at a drug-to-antibody ratio (DAR) of 8 and compared it to Enhertu®, which comprises trastuzumab conjugated to a DXd payload via a (hydrophobic) tetrapeptide linker. The AV-L03 linker makes possible the use of exatecan as a payload for ADCs, which is promising given that exatecan is a more potent inhibitor of TOP1 isomerase compared to DXd, with higher permeability and bystander activity, and is a poorer substrate for some MDR pumps. Moreover, the AV-L03 linker, the shortest hydrophilic linker reported to date, is compatible with diverse payloads, and thus opens up several avenues for the design of superior ADCs."

ADC • Oncology • TOP1

ALTER: A randomized Phase II trial evaluating an upfront alternating regimen of sacituzumab-govitecan and trastuzumab-deruxtecan versus sacituzumab-govitecan alone in HER2-low metastatic triple-negative breast cancer (NCT07151586) (AACR 2026) - P2 | "Abstract is embargoed at this time."

Clinical • Metastases • P2 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2

Preclinical characterization of CGT4255, an EGFR sparing, pan-mutant HER2 clinical development candidate with potential best-in-class brain penetration (AACR 2026) - "The CGT4255 and T-DXd combination demonstrated enhancement of ADC internalization, thus highlighting a biological rationale for combination therapy. In HER2-overexpressed, L755S, YVMA, and T-DXd resistant subcutaneous xenografts, CGT4255 demonstrated dose dependent TGI with tumor regressions observed at dose levels as low as 30 mg/kg."

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

First-line (1L) trastuzumab deruxtecan (T-DXd) + rilvegostomig (rilve) + fluoropyrimidine (FP) in HER2-positive (HER2+) gastric cancer (GC), gastroesophageal junction adenocarcinoma (GEJA), or esophageal adenocarcinoma (EA): DESTINY-Gastric03 (DG-03) Part 4 arm A results (AACR 2026) - "Abstract is embargoed at this time."

Clinical • Late-breaking abstract • Esophageal Adenocarcinoma • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Oncology • Solid Tumor • HER-2

BSI-128 (AK2024) enhances trastuzumab function and potentiates trastuzumab-deruxtecan activity across HER2-positive preclinical models (AACR 2026) - "These data robustly support BSI-128 as a differentiated trastuzumab-synergy antibody with improved performance relative to pertuzumab and the competing synergy antibody when combined with T-Dxd. These findings support the clinical development of BSI-128 plus T-Dxd for HER2-positive gastric cancer and other T-Dxd-approved indications. BSI-128 is currently being evaluated in a Phase 1 clinical trial."

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

BSI-730, a first-in-class HER2xPD-L1 bi-specific ADC, demonstrates potent anti-tumor activity in HER2-low models via selective tumor cell killing and immune modulation (AACR 2026) - "Engaging HER2 and PD-L1 simultaneously enables enhanced internalization, selective tumor cell killing, and promoted anti-tumor immune response via payload-induced immunogenic cell death, subsequently improving efficacy in HER2-low/null patients. The HER2xPD-L1 bi-specific antibody was composed of trastuzumab and the humanized anti-PD-L1 antibody identified from A/J mice immunized with PD-L1-ECD-Fc...The potency of BSI-730 was higher than and comparable to T-Dxd in HER2-low and high expressing cell lines, respectively... BSI-730 is a first-in-class HER2xPD-L1 bi-specific ADC tailored for HER2-low/null patients leveraging dual function of selective cell killing and immune modulation. The current pre-clinical data highlight the potential of BSI-730 in HER2-low setting and further pharmacokinetics, toxicity, and IND-enabling studies are underway."

ADC • Bispecific • IO biomarker • Tumor cell • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

HER2- and TROP2-antibody-drug conjugates in small cell lung cancer cell lines and 3D culture: Efficacy and role of target expression (AACR 2026) - "The growth of these spheroids and PDX organoids were evaluated following treatment with HER2-ADC (trastuzumab deruxtecan), TROP2-ADC (sacituzumab govitecan), tarlatamab, activated T-cells, and combinations of these. Additionally, co-cultured cell line spheroids could provide a better model of tumor heterogeneity. Lastly, HER2- and TROP2- levels are not predictive biomarkers for ADC sensitivity, suggesting that other biomarkers should be explored to identify responsive patient populations."

ADC • IO biomarker • Preclinical • Breast Cancer • Endocrine Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • HER-2 • TACSTD2