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

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

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

Resistance Mechanisms and Post-Trastuzumab Deruxtecan (T-DXd) Strategies in HER2+ and HER2-Low Breast Cancer: From Biology to Clinical Practice. (PubMed, Crit Rev Oncol Hematol) - "Novel agents such as ARX788, patritumab deruxtecan, and Dato-DXd demonstrate promise in overcoming resistance through diversified mechanisms. Real-world data further support a "three-step strategy" involving ADC rechallenge after interim non-ADC therapies, offering a practical, mechanism-informed treatment model. This review provides a framework for precision-guided care in patients with advanced breast cancer and supports ongoing efforts to extend the therapeutic window beyond initial T-DXd benefit."

IO biomarker • Journal • Review • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

A combined strategy of EGFR-MET bispecific antibody and HER3 ADC to overcome osimertinib resistance in NSCLC. (PubMed, Cell Oncol (Dordr)) - "In conclusion, we have proposed a new therapeutic strategy for NSCLC after osimertinib resistance. The combined strategy of amivantamab and patritumab deruxtecan highlight a promising therapeutic avenue, warranting future clinical trials to validate safety and efficacy."

Journal • Lung Cancer • Non Small Cell Lung Cancer • 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

KEYMAKER-06C: Substudy 06C: A Study of Investigational Agents With Pembrolizumab (MK-3475) and Chemotherapy in Participants With First-Line Locally Advanced Unresectable/Metastatic Gastroesophageal Adenocarcinoma (MK-3475-06C/KEYMAKER-U06) (clinicaltrials.gov) - P1/2 | N=160 | Recruiting | Sponsor: Merck Sharp & Dohme LLC | Trial completion date: Apr 2029 ➔ Sep 2029 | Trial primary completion date: Jan 2027 ➔ Sep 2029

Trial completion date • Trial primary completion date • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Adenocarcinoma • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Oncology • Solid Tumor • ERBB3 • HER-2

Substudy 06D: Combination Therapies in Second Line (2L) Gastroesophageal Adenocarcinoma (MK-3475-06D/Keymaker-U06) (clinicaltrials.gov) - P1/2 | N=210 | Recruiting | Sponsor: Merck Sharp & Dohme LLC | Trial completion date: Oct 2028 ➔ Oct 2030

Trial completion date • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Adenocarcinoma • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Oncology • Solid Tumor • ERBB3 • HER-2

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

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

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 (HER3-DXd) in early-stage HR+/HER2- breast cancer: final results of the SOLTI TOT-HER3 window of opportunity trial (ESMO-BC 2022) - P1 | "Conclusions In untreated early HR+/HER2- BC, a single dose of HER3-DXd led to clinically meaningful response, increased immune infiltration and suppression of proliferation across varied levels of baseline ERBB3 mRNA. The safety profile was consistent with that previously reported."

Clinical • Late-breaking abstract • Breast Cancer • Hematological Disorders • HER2 Breast Cancer • HER2 Negative Breast Cancer • Neutropenia • Oncology • Solid Tumor • ERBB3 • HER-2 • SALL4

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

Phase 1 study of patritumab deruxtecan (HER3-DXd; U3-1402) in combination with osimertinib in patients with advanced EGFR-mutated NSCLC. (ASCO 2022) - P1 | "If the RCD includes an osimertinib dose of 80 mg PO QD, ≈30 pts with advanced EGFRm NSCLC without prior treatment will be enrolled and treated at the RCD in a separate cohort; the primary objective is to assess safety and tolerability. A tumor sample after progression with osimertinib (or prior to entry) is required for pts enrolled in dose expansion for retrospective evaluation of HER3 and biomarker analyses."

Clinical • Combination therapy • P1 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • ERBB3

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

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

First Report of Cohort 3 and Mature Survival Data From the U31402-A-U102 Study of HER3‑DXd in EGFR-Mutated NSCLC (JSMO 2023) - No abstract available

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

Patritumab deruxtecan (HER3-DXd) in hormonal receptor-positive/HER2-negative (HR+/HER2-) and triple negative breast cancer (TNBC): results of part B of SOLTI TOT-HER3 window of opportunity trial (ESMO-BC 2023) - P1 | "The safety profile was consistent with that previously reported. Additional correlative analysis will be presented on site."

IO biomarker • Alopecia • Breast Cancer • Constipation • Fatigue • Gastroenterology • Gastrointestinal Disorder • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CD19 • CD8 • ERBB3 • HER-2 • PD-1

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 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

HER2 expression and early response to patritumab deruxtecan (HER3-DXd) in early-stage hormone receptor-positive/HER2-negative (HR+/HER2-) breast cancer (BC): a correlative analysis from SOLTI-TOT-HER3 trial (ESMO-BC 2023) - P1 | "Background HER3-DXd and trastuzumab deruxtecan (T-DXd) are antibody-drug-conjugates (ADCs) directed against HER3 and HER2, respectively. The association of HER2 IHC and ERBB2 mRNA with CelTIL response will be independently validated in TOT-HER3 Part B. Conclusions Low HER2 IHC, mRNA or CN levels in early-stage HR+/HER2- BC are associated with high response to HER3-DXd. HER3-DXd might be highly active in HR+ BC with very low HER2 levels, thereby offering a new therapeutic paradigm to this subset of patients."

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

Patritumab Deruxtecan in Untreated Hormone Receptor-Positive/HER2-Negative Early Breast Cancer: Final Results from Part A of the Window-of-Opportunity SOLTI TOT-HER3 Pre-Operative Study. (PubMed, Ann Oncol) - "A single dose of HER3-DXd was associated with clinical response, increased immune infiltration, suppression of proliferation in HR-positive/HER2-negative early breast cancer, and a tolerable safety profile consistent with previously reported results. These findings support further study of HER3-DXd in early breast cancer."

Journal • Alopecia • Breast Cancer • Fatigue • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Pain • Solid Tumor • ERBB3 • HER-2

A phase 2 study of HER3-DXd in patients (pts) with metastatic breast cancer (MBC). (ASCO 2023) - P2 | "Background: HER3-DXd is an antibody drug conjugate (ADC) comprised of a fully human anti-HER3 IgG1 monoclonal antibody (patritumab), attached to a topoisomerase 1 inhibitor via a tetrapeptide-based cleavable linker that has shown promising efficacy in pts with HER3-expressing MBC (Krop, 2022). HER3-DXd had an acceptable safety profile, and the data further confirm the clinical activity in MBC in heavy pre-tx MBC across the broad range of HER3 expression levels. Parts B and Z are ongoing and data from this report support the potential entry of HER3-DXd into the therapeutic paradigm in MBC. Clinical trial information: NCT04699630."

Clinical • Metastases • P2 data • Alopecia • Anemia • Breast Cancer • Fatigue • Hematological Disorders • Inflammation • Interstitial Lung Disease • Oncology • Pneumonia • Pulmonary Disease • Respiratory Diseases • Solid Tumor • Thrombocytopenia • Triple Negative Breast Cancer • 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

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

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