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oai:recercat.cat:11351/107042025-10-04T05:19:00Zcom_2072_378070com_2072_378040col_2072_378092

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 yu, helena Goto, Yasushi Hayashi, Hidetoshi Yang, James Chih-Hsin Reck, Martin FELIP, ENRIQUETA Institut Català de la Salut [Yu HA] Department of Medicine, Medical Oncology, Memorial Sloan Kettering Cancer Center, New York, USA. [Goto Y] National Cancer Center Hospital, Tokyo, Japan. [Hayashi H] Kindai University, Osaka, Japan. [Felip E] Vall d’Hebron Institute of Oncology (VHIO) Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Chih-Hsin Yang J] National Taiwan University Hospital, Taipei City, Taiwan. [Reck M] Department of Thoracic Oncology, Airway Research Center North, German Center for Lung Research, LungenClinic Grosshansdorf, Grosshansdorf, Germany Vall d'Hebron Barcelona Hospital Campus Pulmons - Càncer - Tractament Pulmons - Càncer - Aspectes genètics Proteïnes quinases - Inhibidors - Ús terapèutic DISEASES::Neoplasms::Neoplasms by Site::Thoracic Neoplasms::Respiratory Tract Neoplasms::Lung Neoplasms::Bronchial Neoplasms::Carcinoma, Bronchogenic::Carcinoma, Non-Small-Cell Lung Other subheadings::Other subheadings::Other subheadings::/drug therapy CHEMICALS AND DRUGS::Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Enzyme Inhibitors::Protein Kinase Inhibitors ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias torácicas::neoplasias del tracto respiratorio::neoplasias pulmonares::neoplasias de los bronquios::carcinoma broncogénico::carcinoma de pulmón de células no pequeñas Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia COMPUESTOS QUÍMICOS Y DROGAS::acciones y usos químicos::acciones farmacológicas::mecanismos moleculares de acción farmacológica::inhibidores enzimáticos::inhibidores de proteínas cinasas Non-small-cell lung cancer; Mutation; Epidermal growth factor Cáncer de pulmón de células no pequeñas; Mutación; Factor de crecimiento epidérmico Càncer de pulmó de cèl·lules no petites; Mutació; Factor de creixement epidèrmic PURPOSE Patritumab deruxtecan, or HER3-DXd, is an antibody-drug conjugate consisting of a fully human monoclonal antibody to human epidermal growth factor receptor 3 (HER3) attached to a topoisomerase I inhibitor payload via a stable tetrapeptide-based cleavable linker. We assessed the efficacy and safety of HER3-DXd in patients with epidermal growth factor receptor (EGFR)–mutated non–small-cell lung cancer (NSCLC). METHODS This phase II study (ClinicalTrials.gov identifier: NCT04619004) was designed to evaluate HER3-DXd in patients with advanced EGFR-mutated NSCLC previously treated with EGFR tyrosine kinase inhibitor (TKI) therapy and platinum-based chemotherapy (PBC). Patients received HER3-DXd 5.6 mg/kg intravenously once every 3 weeks or an uptitration regimen (3.2 → 4.8 → 6.4 mg/kg). The primary end point was confirmed objective response rate (ORR; RECIST 1.1) by blinded independent central review (BICR), with a null hypothesis of 26.4% on the basis of historical data. RESULTS Enrollment into the uptitration arm closed early on the basis of a prespecified benefit-risk assessment of data from the phase I U31402-A-U102 trial. In total, 225 patients received HER3-DXd 5.6 mg/kg once every 3 weeks. As of May 18, 2023, median study duration was 18.9 (range, 14.9-27.5) months. Confirmed ORR by BICR was 29.8% (95% CI, 23.9 to 36.2); median duration of response, 6.4 months; median progression-free survival, 5.5 months; and median overall survival, 11.9 months. The subgroup of patients with previous osimertinib and PBC had similar outcomes. Efficacy was observed across a broad range of pretreatment tumor HER3 membrane expression levels and across diverse mechanisms of EGFR TKI resistance. In patients with nonirradiated brain metastases at baseline (n = 30), the confirmed CNS ORR by BICR per CNS RECIST was 33.3% (95% CI, 17.3 to 52.8). The safety profile (National Cancer Institute Common Terminology Criteria for Adverse Events v5.0) was manageable and tolerable, consistent with previous observations. CONCLUSION 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). 2023-12-18T13:34:13Z 2023-12-18T13:34:13Z 2023-12-10 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Yu HA, Goto Y, Hayashi H, Felip E, Chih-Hsin Yang J, Reck M, et al. 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. J Clin Oncol. 2023 Dec 10;41(35):5363–75. 1527-7755 https://hdl.handle.net/11351/10704 10.1200/JCO.23.01476 37689979 eng Journal of Clinical Oncology;41(35) https://doi.org/10.1200/JCO.23.01476 Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess application/pdf application/pdf American Society of Clinical Oncology Scientia