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

Trastuzumab Botidotin Versus Trastuzumab Emtansine in Human Epidermal Growth Factor Receptor 2-Positive Advanced Breast Cancer: A Phase III, Open-Label, Randomized Controlled Trial. (PubMed, J Clin Oncol) - P3 | "Among patients with HER2-positive advanced BC previously treated with trastuzumab and a taxane, trastuzumab botidotin resulted in significantly longer PFS than trastuzumab emtansine, with a distinct safety profile."

Journal • P3 data • Breast Cancer • Hematological Disorders • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Beamion BCGC-1: Four new phase Ib/II cohorts to evaluate oral zongertinib with other agents in HER2-positive metastatic breast cancer (mBC) and metastatic colorectal cancer (mCRC). (ASCO 2026) - P1/2 | "Trial details for Cohorts A–K, evaluating zongertinib as monotherapy or combined with T-DM1, T-DXd, or trastuzumab ± capecitabine in patients (pts) with HER2-positive mBC, and with T-DXd in pts with HER2-positive metastatic gastric, gastroesophageal junction, or esophageal adenocarcinoma (mGEAC), have recently been published (Hurvitz et al, Future Oncol 2025)...Here, we report 4 new cohorts (L–O) to evaluate the efficacy and safety of zongertinib plus zanidatamab in HER2-positive mBC, or plus trastuzumab or mFOLFOX6 ± trastuzumab in HER2-positive mCRC...In Ph II, the primary endpoint is OR by RECIST v1.1; secondary endpoints include PFS, disease control, AEs leading to dose reduction, PK, and pt-reported outcomes. Pts will remain on treatment until any protocol-defined stopping criterion occurs."

Metastases • New P1/2 trial • P1/2 data • Breast Cancer • Colorectal Cancer • Esophageal Adenocarcinoma • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • EGFR • HER-2

Primary results from a phase 2a study of zanidatamab (zani) + palbociclib (palbo) + fulvestrant (fulv) in HER2+/HR+ metastatic breast cancer (mBC) (SABCS 2023) - P2 | " Eligible pts had HER2+ (by local HER2 testing) and HR+, unresectable, locally advanced or mBC; ECOG PS ≤1; prior treatment with at least trastuzumab, pertuzumab, and T-DM1; and no prior CDK4/6 inhibitor...In the metastatic setting, pts received a median (range) of 4 (1-12) prior systemic regimens, 3 (1-10) prior different HER2-targeted therapies, and 1 (0-5) prior endocrine therapy; 12 (24%) pts had prior T-DXd and 11 (22%) had prior fulv... Zani + palbo + fulv showed a promising PFS6 and mPFS with durable responses. The safety profile was manageable. These results support further development of a novel chemotherapy-free treatment regimen for heavily pretreated pts with HER2+/HR+ mBC."

Late-breaking abstract • Metastases • P2a data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Beamion BCGC-1: Phase Ib/II Trial of Zongertinib Monotherapy/Combination Therapy - Evaluation of a Cohort of Advanced HER2-Positive Metastatic Breast Cancer (JBCS 2026) - P1/2 | "The Beamion BCGC-1 trial (NCT06324357) is a phase Ib/II trial evaluating zongertinib monotherapy or combination therapy with T-DM1, T-DXd, trastuzumab ± capecitabine, or zanidatamab in patients with HER2-positive metastatic breast cancer (mBC) and gastric cancer (GC)/colorectal cancer (CRC), with eight participating centers from Japan. The primary endpoint of Phase II is ORR (RECIST v1.1), with secondary endpoints including progression-free survival (PFS), disease control, adverse events leading to dose reduction, pharmacokinetics (PK), and patient-reported outcomes. Treatment will continue until protocol-defined discontinuation criteria are met."

Combination therapy • Metastases • Monotherapy • P1/2 data • Breast Cancer • Colorectal Cancer • Gastric Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Zanidatamab (Zani) + chemotherapy (Chemo) for patients (Pts) with HER2-expressing metastatic breast cancer (mBC): Final results of a phase I trial (ESMO-BC 2025) - P1 | "We report the final analysis of a phase I trial of zani + chemo in pts with HER2-expressing mBC. Part 3 of the phase I trial (NCT02892123) evaluated zani + chemo (paclitaxel [pac], capecitabine [cap] or vinorelbine [vin]) or zani + cap + tucatinib (tuc) in pts with HER2-expressing mBC...Prior (>5% of pts) anti-HER2 therapies included trastuzumab (93%), T-DM1 (91%), pertuzumab (80%), lapatinib (24%), T-DXd (9%), tuc (9%), and neratinib (7%)... Zani + chemo had a manageable safety profile and good tolerability with promising antitumour activity and durable responses in heavily pretreated pts with HER2-expressing mBC. Among pts with HER2+ mBC with prior HER2-targeted regimens, adding zani to chemo showed encouraging PFS."

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

CLINICAL OUTCOMES WITH TRASTUZUMAB EMTANSINE OR IPATASERTIB PLUS PACLITAXEL FOR PERSISTENT/RECURRENT RARE EPITHELIAL OVARIAN CARCINOMAS: ENGOT-GYN2/GOG-3051/BOUQUET PHASE 2 BIOMARKER-DIRECTED STUDY (IGCS 2024) - P2 | "Ipatasertib+paclitaxel demonstrated more encouraging activity. The tolerability of both regimens was consistent with previous experience."

Biomarker • Clinical • Clinical data • P2 data • Oncology • Ovarian Cancer • Solid Tumor • AKT1 • HER-2 • PIK3CA • PTEN

Cost-utility analysis of trastuzumab deruxtecan versus trastuzumab emtansine as second-line treatment for HER2-positive metastatic breast cancer. (PubMed, Expert Rev Pharmacoecon Outcomes Res) - "T-DXd does not demonstrate a cost-effectiveness advantage over T-DM1 at the current WTP threshold in China. However, given the ICER's proximity of the threshold, price reductions or regional economic variation may improve its cost-effectiveness."

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

Safety, tolerability, pharmacokinetics, and antitumor activity of SHR-A1811 in HER2-expressing/mutated advanced solid tumors: A global phase 1, multi-center, first-in-human study (AACR 2023) - "Background: SHR-A1811 is an ADC comprised of a humanized anti-HER2 monoclonal antibody (trastuzumab), a cleavable linker, and a DNA topoisomerase I inhibitor payload. SHR-A1811 was well-tolerated and showed promising antitumor activity in heavily pretreated advanced solid tumors.Table 1. Subgroup analyses of ORRNo. of prior treatment lines in metastatic setting in all pts (N=250)HER2 positive BC (N=108)HER2-low BC (N=77)Other tumor types (N=65)≤381.8% (45/55)58.7% (27/46)36.7% (18/49)>381.1% (43/53)51.6% (16/31)31.3% (5/16)Prior anti-HER2 therapies in pts with BC (N=185)*HER2 positive BC (N=108)HER2-low BC (N=77)All BC (N=185)Any82.2% (88/107, 73.7-89.0)68.8% (11/16, 41.3-89.0)80.5% (99/123, 72.4-87.1)Trastuzumab81.9% (86/105, 73.2-88.7)75.0% (9/12, 42.8-94.5)81.2% (95/117, 72.9-87.8)Pertuzumab83.0% (39/47, 69.2-92.4)100% (5/5, 47.8-100)84.6% (44/52, 71.9-93.1)Pyrotinib86.9% (53/61, 75.8-94.1)71.4% (5/7, 29.0-96.3)85.3% (58/68, 74.6-92.7)Lapatinib80.0% (28/35,..."

Clinical • Metastases • P1 data • PK/PD data • Biliary Cancer • Biliary Tract Cancer • Breast Cancer • Colorectal Cancer • Endometrial Cancer • Gastric Cancer • Gastrointestinal Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Urothelial Cancer • HER-2

[VIRTUAL] Local Therapy Outcomes and Toxicity From the ATEMPT Trial (TBCRC 033), a Phase II Randomized Trial of Adjuvant T-DM1 vs. TH in Women With Stage I HER2 Positive Breast Cancer (ASTRO 2021) - "Materials/ The ATEMPT trial is a prospective randomized phase II study of adjuvant ado-trastuzumab emtansine (T-DM1) vs paclitaxel (T) and trastuzumab (H) following either mastectomy (M) or breast conserving surgery (BCS) in women with stage I HER2+ breast cancer. RT was well-tolerated when given concurrently with either T-DM1 or H, regardless of fractionation. Local recurrences were unlikely, attesting to the efficacy of highly effective HER2-directed therapy with RT, and suggesting opportunities for future study of RT de-escalation."

Clinical • P2 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Musculoskeletal Diseases • Oncology • Pneumonia • Solid Tumor • HER-2

Real-World Insights Into Clinical, Molecular, Treatment Patterns and Outcomes of HER2-altered Lung Cancer in Western India (IASLC-WCLC 2026) - "A total of n=13 patients received anti-HER2 therapy in any lines of their treatment & n=7 used it in the first-line; overall Trastuzumab, Trastuzumab Emtansine, Trastuzumab Deruxtecan were used in n=6, n=4, n=3 respectively. mOS was 26.03 months with T-DM1 vs 16.98 months with trastuzumab p=0.008. Conclusions : This study provides real-world evidence on the molecular characteristics, treatment patterns, and clinical outcomes of HER2-altered lung cancer in Indian community oncology settings, highlighting its evolving role in guiding precision-based therapeutic strategies."

Clinical • Real-world • Real-world evidence • Lung Cancer • Oncology • Solid Tumor • EGFR • HER-2 • KRAS • TP53

Trastuzumab deruxtecan (T-DXd) versus trastuzumab emtansine (T-DM1) in patients (pts) with HER2-positive (HER2+) unresectable and/or metastatic breast cancer (mBC): Safety follow-up of the randomized, phase 3 study DESTINY-Breast03. (ASCO 2022) - P3 | "In this updated safety analysis, T-DXd demonstrated a tolerable safety profile consistent with prior studies. Despite longer treatment duration with T-DXd, EAIRs of G≥3 and SAEs were lower for T-DXd vs T-DM1. Rates of ILD/pneumonitis for T-DXd were similar to those in the previous DCO."

Clinical • P3 data • Alopecia • Anemia • Breast Cancer • Fatigue • Gastrointestinal Disorder • Hematological Disorders • HER2 Breast Cancer • HER2 Positive Breast Cancer • Inflammation • Leukopenia • Neutropenia • Oncology • Pneumonia • Solid Tumor • Thrombocytopenia • HER-2

Early identification of interstitial lung disease risk while measuring ADC efficacy in a human systemic in vitro platform (ERS 2026) - "As clinical benchmarks, we evaluated T-DXd and free Exatecan...To probe the contribution of DXd-based payload chemistry across targets, we evaluated Patritumab deruxtecan (P-DXd), a HER3-targeting DXd ADC...In alignment with clinical observations, T-DM1 did not induce injury signature to the lung. This integrated assay de-risks ADC programs by simultaneously quantifying tumor efficacy and lung safety in a human-relevant platform."

ADC • Preclinical • Fibrosis • Interstitial Lung Disease • Pulmonary Disease • Respiratory Diseases • ERBB3 • HER-2

Trastuzumab deruxtecan versus trastuzumab emtansine in HER2-positive metastatic breast cancer patients with brain metastases from the randomized DESTINY-Breast03 trial. (PubMed, ESMO Open) - "Patients with HER2-positive mBC whose disease progressed after trastuzumab and a taxane achieved a substantial benefit from treatment with T-DXd compared with T-DM1, including those with baseline BMs."

Clinical • Journal • Metastases • P3 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Spatially Driven DNA-Based Probe Proximity Assay for Total Antibody Quantification in Antibody-Drug Conjugates. (PubMed, ACS Sens) - "Moreover, the proposed homogeneous detection method achieved superior recovery for trastuzumab and successfully quantified total antibodies in trastuzumab emtansine (T-DM1) and trastuzumab deruxtecan (T-DXd). Finally, the proposed assay was applied to a series of spiked serum samples and clinical samples, demonstrating its feasibility and proof of concept. This strategy may facilitate the development of bioanalytical techniques for ADC characterization and monitoring."

Journal

FINAL outcome ANALYSIS FROM THE PHASE II TUXEDO-1 TRIAL OF TRASTUZUMAB-DERUXTECAN IN HER2-positive breast cancer PATIENTS WITH active brain metastases. (PubMed, Neuro Oncol) - "T-DXd yielded prolonged intra- and extracranial disease control in patients with active HER2-positive BC BM in line with results from the pivotal trials. These results support the concept of ADCs as systemic therapy for active BM."

Journal • P2 data • Breast Cancer • Fatigue • HER2 Breast Cancer • HER2 Positive Breast Cancer • Interstitial Lung Disease • Oncology • Pulmonary Disease • Respiratory Diseases • Solid Tumor • HER-2

Treatment-Related Toxicities of Antibody-Drug Conjugates in Breast Cancer: A Bayesian Network Meta-Analysis. (PubMed, Cancer Control) - "The protocol was registered in PROSPERO (CRD42024606194).ResultsSeventeen randomized trials including 8,946 patients and five ADCs-trastuzumab emtansine (T-DM1), sacituzumab govitecan (SG), trastuzumab deruxtecan (T-DXd), datopotamab deruxtecan (Dato-DXd), and ARX788-were analyzed. For gastrointestinal toxicities, SG ranked worst for diarrhea (SUCRA 6.0%), whereas T-DXd was associated with higher risks of nausea (2.2%), vomiting (7.9%), and decreased appetite (8.6%). In analyses of SAEs, SG had the highest rates of anemia (11.7%) and neutropenia (8.5%), while gastrointestinal SAEs occurred more frequently with T-DXd.ConclusionsThis network meta-analysis highlights clinically meaningful differences in ADC safety profiles and may help guide individualized toxicity management in breast cancer."

Clinical • Journal • Retrospective data • Review • Breast Cancer • Hematological Disorders • Neutropenia • Oncology • Solid Tumor • Thrombocytopenia

Beamion BCGC-1: A phase Ib/II trial of the HER2-selective tyrosine kinase inhibitor (TKI) zongertinib (BI 1810631) + trastuzumab deruxtecan (T-DXd) or trastuzumab emtansine (T-DM1) for patients with metastatic breast cancer (mBC) and metastatic gastric, gastroesophageal junction, or esophageal adenocarcinoma (mGEAC). (ASCO-GI 2025) - P1, P1/2 | "Patients will remain on treatment until disease progression, undue toxicity or any other protocol-defined stopping criterion. Enrollment is ongoing."

Clinical • Metastases • P1/2 data • Esophageal Adenocarcinoma • Esophageal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • EGFR • HER-2

Trastuzumab deruxtecan vs physician’s choice in patients with HER2+ unresectable and/or metastatic breast cancer previously treated with trastuzumab emtansine: primary results of the randomized, phase 3 study DESTINY-Breast02 (SABCS 2022) - P2, P3 | "Methods Pts with HER2+ mBC were randomized 2:1 to receive T-DXd or TPC (trastuzumab + capecitabine or lapatinib + capecitabine) and stratified by hormone receptor (HR) status (HR+/HR-), prior pertuzumab treatment, and history of visceral disease. Conclusions Results from DESTINY-Breast02 confirmed the clinical benefit and superiority of T-DXd over conventional chemotherapy-based regimens in pts with HER2+ mBC previously treated with T-DM1, as evidenced by significant and clinically meaningful improvements in PFS and OS. These data, together with earlier reported results from the DESTINY-Breast03 study of T‑DXd vs T-DM1 solidify T-DXd as an optimal treatment option in pts with progressive HER2+ mBC across broad settings."

Clinical • P3 data • Breast Cancer • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • HER-2

Novel integrated tumor micro-/macro-environment (TMME) subtypes for prediction of treatment response to neoadjuvant anti-HER2 therapy (ESMO-BC 2025) - P2/3 | "We developed novel integrated TMME subtypes with distinct clinical outcomes in patients with early HER2-positive BC, highlighting the importance of evaluating tumor macro- and microenvironment for therapy response to antibody-drug conjugates."

Clinical • IO biomarker • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • CD4 • CD8 • ER • HER-2 • IL33

Patient-Reported Outcomes (PROs) From DESTINY-Breast05: Health-Related Quality of Life (HRQoL) With Trastuzumab Deruxtecan (T-DXd) Versus Trastuzumab Emtansine (T-DM1) in Patients (Pts) With High-Risk HER2-Positive Early Breast Cancer (eBC) (ESMO 2026) - No abstract available

Clinical • HEOR • Patient reported outcomes • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Adjuvant trastuzumab emtansine in HER2-positive breast cancer patients with HER2-negative residual invasive disease in KATHERINE. (PubMed, NPJ Breast Cancer) - "We evaluated outcomes with T-DM1 and trastuzumab in patients randomized in the phase III KATHERINE trial based on HER2-positive central testing of the pre-treatment core biopsy with HER2-negative central testing on their corresponding surgical specimen after neoadjuvant treatment. In the 70/845 (8.3%) patients with HER2-negative residual disease on retesting at surgery, there were 11 IDFS events in the 42 trastuzumab-treated patients (26.2%) and none in the 28 T-DM1-treated patients, suggesting that T-DM1 should not be withheld in this patient population."

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

Treatment discontinuation, patient-reported toxicities and quality-of-life by age following trastuzumab emtansine or paclitaxel/trastuzumab (ATEMPT). (PubMed, NPJ Breast Cancer) - P2 | "Older women had decreased neuropathy with T-DM1 vs. TH. De-escalated treatment regimens for HER2 positive breast cancer may have age-varying impact on treatment tolerance, toxicities and subsequent QOL, which should be considered when selecting therapy options.Clinical Trial Registration: ClinicalTrials.gov, NCT01853748."

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

A single-arm, phase II study of sequential therapy with curative intent in de novo HER2+ metastatic breast cancer: The SAPPHO study. (ASCO 2026) - P2 | "Treatment consists of an induction regimen (trastuzumab-pertuzumab-taxane [THP] x 4 cycles, followed by trastuzumab deruxtecan [TDXd] x 6 cycles, followed by trastuzumab emtansine [TDM1]-tucatinib x 4 cycles), followed by a maintenance regimen (HP-tucatinib for 1 yr). Patient-reported outcomes will be analyzed, including quality of life, illness intrusiveness, financial toxicity, anxiety, distress about cancer progression, perception of benefit and risk of progression. SAPPHO began enrollment in Q3 2024, and the study is open at 4 US sites within the Translational Breast Cancer Research Consortium (NCT05721248)."

Metastases • P2 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Mood Disorders • Oncology • Solid Tumor • HER-2

Pertuzumab retreatment for HER2-positive advanced breast cancer: a randomized, open-label phase III study (PRECIOUS). (PubMed, Cancer Sci) - "No standard options existed for HER2-positive advanced breast cancer that progresses after second-line trastuzumab emtansine therapy (T-DM1) before 2020. The incidence of treatment-related adverse events was similar between groups except for diarrhoea. Pertuzumab retreatment contributes to disease control for HER2-positive locally advanced or metastatic breast cancer previously treated with pertuzumab-containing regimens."

Journal • P3 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Clinical outcomes and genomic landscape of anti-HER2 antibody-drug conjugates in HER2-positive and HER2-low metastatic breast cancer. (PubMed, Ther Adv Med Oncol) - "Patients with HER2-positive or HER2-low MBC who received anti-HER2 ADCs (T-DXd, SHR-A1811, RC48, or T-DM1) between September 1, 2020, and September 1, 2024, were enrolled. Distinct genomic alterations, especially MYC amplification, were associated with poorer outcomes, underscoring the need for biomarker-driven strategies. These descriptive findings should be interpreted with caution and require prospective validation."

Clinical data • Journal • Breast Cancer • Fatigue • Hematological Disorders • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Pneumonia • Solid Tumor • CCND1 • FGF19 • MYC • TP53