patritumab deruxtecan (U3-1402) / Daiichi Sankyo, Merck (MSD) - LARVOL DELTA

Patritumab Deruxtecan (HER3-DXd) in Melanoma After Anti-PD-(L)1 Therapy: Primary Analysis From HERTHENA-PanTumor01 (ESMO 2026) - No abstract available

Pan tumor • Melanoma • Oncology • Solid Tumor • ERBB3

Final results of the TUXEDO-3 phase II trial of patritumab deruxtecan (HER3-DXd) in active brain metastases (BMs) and leptomeningeal disease (LMD) (ESMO 2026) - No abstract available

Clinical • P2 data • Oncology • Solid Tumor • ERBB3

KEYMAKER-U01 substudy 01A: Phase 1/2 study of pembrolizumab plus ifinatamab deruxtecan (I-DXd) or patritumab deruxtecan (HER3-DXd) with or without chemotherapy in untreated stage IV non–small-cell lung cancer. (ASCO 2025) - P1/2 | "KEYMAKER-U01 substudy 01A (NCT04165070) is a phase 1/2, two-part, rolling arm, open-label study assessing the efficacy and safety of pembrolizumab plus an investigational agent (part A: vibostolimab, boserolimab, MK-4830, and MK-0482; part B: I-DXd and HER3-DXd), with or without chemotherapy in untreated stage IV NSCLC...In Arms 5 and 6, participants will receive I-DXd plus pembrolizumab 200 mg Q3W (Arm 5) or I-DXd plus pembrolizumab with 4 cycles of carboplatin area under the curve 5 or 6 mg/ml/min (Arm 6); I-DXd dose will be at 8mg/kg...The primary endpoint is incidence of dose-limiting toxicities until the start of cycle 2, and AEs and treatment discontinuations due to AEs until 40 days after last treatment (90 days for serious AEs); secondary endpoints include ORR and DOR, both per RECIST v1.1 by BICR, and pharmacokinetic parameters, including maximum concentration (Cmax) and maximum trough concentration (Ctrough) of I-DXd and HER3-DXd. Enrollment will be..."

IO biomarker • Metastases • P1/2 data • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • ERBB3 • HER-2 • ROS1

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

Patritumab Deruxtecan (HER3-DXd) in EGFR-Mutated NSCLC Following EGFRTKI and Platinum-Based Chemotherapy: HERTHENA-Lung01 (IASLC-WCLC 2023) - P1, P2, P3 | "Patients with prior osimertinib had similar outcomes (Table). In this patient population with significant unmet need and limited therapeutic options, HER3-DXd demonstrated clinically meaningful efficacy; moreover, this study provides the first report of HER3-DXd efficacy in the CNS. The safety profile was manageable and, overall, HER3-DXd is a promising therapy for patients with previously treated EGFR-mutated NSCLC. A phase 3 trial in EGFR-mutated NSCLC after progression on EGFR TKI is ongoing (HERTHENA-Lung02; NCT05338970)."

Interstitial Lung Disease • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pulmonary Disease • Respiratory Diseases • Solid Tumor • ERBB3

Patritumab Deruxtecan (HER3-DXd; MK-1022) in Non-Small Cell Lung Cancer After Platinum-Based Chemotherapy and Immunotherapy. (PubMed, J Clin Oncol) - "The previously reported efficacy and safety of HER3-DXd in heavily pretreated patients with EGFR-mutated NSCLC are also observed in those with other NSCLC subtypes and warrant further clinical evaluation."

IO biomarker • Journal • Interstitial Lung Disease • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Pulmonary Disease • Respiratory Diseases • Solid Tumor • EGFR • ERBB3

Results from the phase 1/2 study of patritumab deruxtecan, a HER3-directed antibody-drug conjugate (ADC), in patients with HER3-expressing metastatic breast cancer (MBC). (ASCO 2022) - P1/2 | "A pooled analysis in this heavily pretreated population showed promising efficacy in pts with HR+/HER2− and HER2+ MBC as well as TNBC. The safety profile with longer follow-up is consistent with previous reports and showed adequate safety and tolerability. Studies are ongoing in MBC tumor types, with a focus on biomarkers associated with efficacy."

Clinical • P1/2 data • Anemia • Breast Cancer • Hematological Disorders • Interstitial Lung Disease • Oncology • Pulmonary Disease • Respiratory Diseases • Solid Tumor • Triple Negative Breast Cancer • HER-2

Patritumab deruxtecan in HR+HER2- advanced breast cancer: a phase 2 trial. (PubMed, Nat Med) - P2 | "Overall, HER3-DXd showed promising activity and manageable tolerability in patients with HR+HER2- metastatic breast cancer who progressed on CDK4/6 inhibitors. These findings highlight the need for larger trials to define HER3-DXd efficacy relative to other drugs, including antibody-drug conjugates (ClinicalTrials.gov Identifier: NCT04965766 )."

Journal • P2 data • Alopecia • Breast Cancer • Fatigue • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Immunology • Oncology • Solid Tumor • ER • ERBB3 • HER-2

Patritumab deruxtecan in HER2-negative breast cancer: part B results of the window-of-opportunity SOLTI-1805 TOT-HER3 trial and biological determinants of early response. (PubMed, Nat Commun) - "Critically, low HER2DX ERBB2 mRNA, correlates with increased HER3-DXd activity, which is validated through in vivo patient-derived xenograft  models. This study proposes chemosensitivity determinants, DNA-based subtype classification, and low ERBB2 expression as potential markers for HER3-DXd activity in HER2-negative breast cancer."

Journal • 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 • CCNE1 • ERBB3 • HER-2 • SLC39A6 • TP53

Primary results of SOLTI VALENTINE: neoadjuvant randomized phase II trial of HER3-DXd alone or in combination with letrozole for high-risk hormone receptor positive (HR+)/HER2-negative (neg) early breast cancer (EBC). (SABCS 2024) - P2 | "Pts were randomized 2:2:1 to: (A) HER3-DXd 5.6 mg/kg every (Q) 21 days (D) for 6 cycles; (B) HER3-DXd plus QD LET (+/- LHRH agonist); (C) CT with 4 cycles of EC/AC (epirubicin 90 mg/m2 or doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2 Q14 or 21 D) followed by weekly paclitaxel 80mg/m2 for 12 weeks. In SOLTI VALENTINE, treatment with HER3-DXd, with or without LET, resulted in similar pCR rates to CT, while exhibiting a lower incidence of grade ≥3 TEAEs. CelTIL score at C2D1 correlated with response to HER3-DXd, but not to CT. The ongoing translational analysis, as well as the survival outcomes of VALENTINE, will provide further insights into the activity of HER3-DXd in EBC and clarify its potential role as a treatment strategy for high-risk HR+/HER2-neg breast cancer."

Clinical • Combination therapy • Late-breaking abstract • P2 data • 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 • ERBB3 • HER-2

A randomised phase 2 trial of neoadjuvant multi-agent chemotherapy (CHT) OR patritumab deruxtecan (HER3-DXd; U3-1402) +/- endocrine therapy (ET) for high-risk hormone receptor positive (HR+/HER2-) early breast cancer (EBC): SOLTI-2103 VALENTINE trial (ESMO-BC 2023) - P2 | "Trial design VALENTINE is a parallel, exploratory, three-arm, randomised, open-label, exploratory study in pts with primary operable HR+/HER2-negative breast cancer with Ki67 IHC ≥ 20% and/or high genomic risk (defined by gene signature), aiming to evaluate the clinical benefit and biological effects of HER3-DXd (with/without letrozole (LET)) as a neoadjuvant treatment. A total of 120 treatment naïve pts will be randomly assigned in a 2:2:1 ratio to receive (1) HER3-DXd (5.6 mg/kg) every 21 days for 6 cycles; (2) HER3-DXd plus daily LET +/- LHRH analogs every 21 days for 6 cycles; (3) standard of care CHT consisting of 4 cycles of EC/AC (epirubicin 90 mg/m2 or doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2 every 14/21 days) followed by weekly 80mg/m2 paclitaxel during 12 weeks...Secondary endpoints include rate of residual cancer burden, overall response rate, invasive disease-free survival at 3 and 5 years and safety. An interim and final analysis are..."

Clinical • P2 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ERBB3 • HER-2

Intracranial efficacy of HER3-DXd in patients with previously treated advanced EGFR-mutated NSCLC: Results from HERTHENA-Lung01 (ESMO 2023) - P2 | "a CR + PR. b 11 pts with CR only had nontarget lesions"

Clinical • Metastases • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • ERBB3

A phase 2 Study of Patritumab Deruxtecan (HER3-DXd), in patients (pts) with advanced breast cancer (ABC), with biomarker analysis to characterize response to therapy (ICARUS-BREAST01) (ESMO-BC 2023) - P1/2, P2 | "Conclusions HER3-DXd showed early signs of activity and a manageable safety profile in pts with HR+ HER2- ABC. Results on biomarkers analysis will also be presented."

Biomarker • Clinical • Metastases • P2 data • Breast Cancer • Fatigue • HER2 Breast Cancer • Oncology • Solid Tumor • CDK4 • CTCs • ERBB3 • HER-2 • TOP1

A phase II study of patritumab deruxtecan (HER3-DXd) in patients (pts) with metastatic breast cancer (MBC) (ESMO-BC 2026) - P2 | "Part Z enrolled pts with HER2+ MBC and prior tx with trastuzumab deruxtecan. Efficacy in Part A (ADC naïve) was clinically meaningful, supporting development of HER3-DXd in earlier-line settings. In contrast, limited activity was observed in Parts B and Z (tx w/ prior ADC with topoisomerase I payload) with HER3-DXd monotherapy. No cumulative toxicity was observed, and overall safety findings were consistent with previous studies."

Clinical • Metastases • P2 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ERBB3 • HER-2 • TOP1

HERTHENA-Lung01, a Phase II Trial of Patritumab Deruxtecan (HER3-DXd) in Epidermal Growth Factor Receptor-Mutated Non-Small-Cell Lung Cancer After Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Therapy and Platinum-Based Chemotherapy. (PubMed, J Clin Oncol) - P2, P3 | "After tumor progression with EGFR TKI therapy and PBC in patients with EGFR-mutated NSCLC, HER3-DXd once every 3 weeks demonstrated clinically meaningful efficacy with durable responses, including in CNS metastases. A phase III trial in EGFR-mutated NSCLC after progression on an EGFR TKI is ongoing (HERTHENA-Lung02; ClinicalTrials.gov identifier: NCT05338970)."

Journal • P2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • ERBB3 • HER-2

Patritumab deruxtecan (HER3-DXd) in resistant EGFR-mutated (EGFRm) advanced non-small cell lung cancer (NSCLC) after a third-generation EGFR TKI: The phase 3 HERTHENA-Lung02 study. (ASCO 2025) - P3 | "HER3‑DXd demonstrated statistically significant improvement in PFS vs PBC in pts with EGFRm NSCLC post EGFR TKI therapy. The safety profile was manageable, consistent with prior reports. Most common TEAEs were hematologic and gastrointestinal."

Metastases • P3 data • Fatigue • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thrombocytopenia • ERBB3

Genetic determinants of response to patritumab deruxtecan (HER3-DXd) in hormone receptor-positive/HER2-negative (HR+/HER2-) breast cancer: a correlative analysis from SOLTI TOT-HER3 trial (SABCS 2022) - P1 | "TP53 mutations, immune-related genes, and DNA/RNA-based phenotypic signatures tracking Basal- or Luminal A-related biology such as the DNA-based RB-LOH score or the endocrine sensitivity score (Scorr_IE_Correlation) are associated with CelTIL changes in response to HER3-DXd in HR+/HER2- breast cancer. Further RNA- and DNA-based analyses will be evaluated."

IO biomarker • Breast Cancer • Eye Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Retinoblastoma • Solid Tumor • CCNE1 • CD68 • ERBB3 • HER-2 • PD-1 • PIK3CA • TMB • TP53

Efficacy and safety of patritumab deruxtecan (HER3-DXd) in advanced/metastatic non-small cell lung cancer (NSCLC) without EGFR-activating mutations. (ASCO 2022) - P1, P2 | "These data show promising clinical activity in pts with NSCLC without EGFRm, including pts with other identified driver genomic alterations. Updated results from this study will be presented. The overall safety profile was similar to that previously reported in pts with EGFRm NSCLC."

Clinical • IO biomarker • Fatigue • Hematological Disorders • Interstitial Lung Disease • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Neutropenia • Non Small Cell Lung Cancer • Oncology • Pulmonary Disease • Respiratory Diseases • Solid Tumor • Thrombocytopenia • ALK • EGFR • ERBB3 • KRAS • NRAS • ROS1

Efficacy, safety and biomarker analysis of ICARUS-BREAST01: A phase II study of patritumab deruxtecan (HER3-DXd) in patients (pts) with HR+/HER2- advanced breast cancer (ABC) (ESMO 2024) - P2 | "HER3-DXd showed clinically meaningful activity and manageable safety profile in patients with HR+/HER2- ABC progressing after 2 or more lines of therapy. Further studies are warranted to confirm the role of HER3-DXd in this setting."

Biomarker • Clinical • Metastases • P2 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ERBB3 • HER-2 • TOP1

HER3 expression and overall survival (OS) in ICARUS-BREAST01: A phase II study with patritumab deruxtecan (HER3-DXd) patients (pts) with HR+/HER2- advanced breast cancer (ABC) (ESMO-BC 2026) - P2 | "HER3-DXd demonstrated clinically meaningful efficacy and manageable safety in pts with pretreated HR+/HER2- ABC. A trend toward longer OS was observed in pts with higher HER3 expression. Further data on the correlation between HER3 expression and clinical outcome and exploratory biomarker analyses will be presented."

Clinical • Metastases • P2 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ERBB3 • HER-2

Patritumab deruxtecan in leptomeningeal metastatic disease of solid tumors: the phase 2 TUXEDO-3 trial. (PubMed, Nat Med) - P2 | "TUXEDO-3 showed clinically relevant HER3-DXd activity in patients with LMD. ClinicalTrials.gov identifier: NCT05865990 ."

Journal • P2 data • Breast Cancer • Hematological Disorders • Lung Cancer • Neutropenia • Oncology • Pain • Solid Tumor • Thrombocytopenia • ERBB3

Patritumab deruxtecan (HER3-DXd) in active brain metastases (BM) from metastatic breast (mBC) and non–small cell lung cancers (aNSCLC), and leptomeningeal disease (LMD) from advanced solid tumors: Results from the TUXEDO-3 phase II trial. (ASCO 2025) - P2 | "TUXEDO-3 is the first trial evaluating efficacy and safety of HER3-DXd in pts with BM or LMD. HER3-DXd showed substantial CNS activity in parenchymal metastases and LMD, and may be a potential novel treatment for CNS disease in cancer pts."

Metastases • P2 data • CNS Disorders • CNS Tumor • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • ERBB3 • HER-2

Incidence and Severity of Interstitial Lung Disease Associated With Antibody-Drug Conjugates in NSCLC and SCLC: A Meta-Analysis (IASLC-WCLC 2025) - "In NSCLC, the highest pooled incidence of any-grade ILD was seen with patritumab deruxtecan (23%) and trastuzumab deruxtecan (22%), followed by datopotamab deruxtecan (9%), telisotuzumab vedotin (7%), and sacituzumab govitecan (1%)...Treatment discontinuation due to ILD in NSCLC was highest with telisotuzumab vedotin combined with erlotinib (36%), followed by trastuzumab deruxtecan (9%) and patritumab deruxtecan (7%)...In SCLC, any-grade ILD incidence was 8% with rovalpituzumab tesirine, with no reported grade ≥3 ILD events...HER2/HER3-targeted, deruxtecan-containing ADCs demonstrated the highest ILD rates, while other ADCs such as sacituzumab govitecan had minimal reported toxicity. These findings highlight the need for agent-specific ILD monitoring and support the consideration of ADC design, including target and payload, when evaluating pulmonary safety and guiding clinical decision-making."

Retrospective data • Interstitial Lung Disease • Lung Cancer • Non Small Cell Lung Cancer • Pulmonary Disease • Respiratory Diseases • Small Cell Lung Cancer • Solid Tumor • ERBB3 • HER-2

KEYMAKER-U01F: Umbrella Study of Novel Therapies in Previously Treated Advanced/Metastatic Nonsquamous KRAS G12C-Mutant NSCLC (IASLC-WCLC 2026) - P1/2 | "The phase 1b/2 KEYMAKER-U01 substudy F (NCT07286149) will evaluate calderasib in combination with novel therapies, including the HER3-directed antibody-drug conjugate patritumab deruxtecan (HER3-DXd; MK-1022), the TROP2-directed antibody-drug conjugate sacituzumab tirumotecan (sac-TMT; MK-2870), and cetuximab in previously treated advanced or metastatic nonsquamous KRAS G12C-mutant NSCLC. Secondary endpoints include DOR and PFS per RECIST v1.1 by BICR and pharmacokinetic parameters including area under the curve, maximum plasma concentration, and minimum observed concentration. The study is currently enrolling at an anticipated 61 global sites."

IO biomarker • Metastases • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Solid Tumor • KRAS

Patritumab Deruxtecan (HER3-DXd), a Human Epidermal Growth Factor Receptor 3-Directed Antibody-Drug Conjugate, in Patients With Previously Treated Human Epidermal Growth Factor Receptor 3-Expressing Metastatic Breast Cancer: A Multicenter, Phase I/II Trial. (PubMed, J Clin Oncol) - "HER3-DXd demonstrated a manageable safety profile and durable efficacy in heavily pretreated patients across clinical subtypes. These data warrant further evaluation of HER3-DXd in patients with HER3-expressing metastatic breast cancer."

Journal • Metastases • P1/2 data • Breast Cancer • Hematological Disorders • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Interstitial Lung Disease • Oncology • Pulmonary Disease • Respiratory Diseases • Solid Tumor • Triple Negative Breast Cancer • ERBB3 • HER-2