{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Yu HA"],"funding":["NCI NIH HHS"],"pagination":["5363-5375"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10713116"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["41(35)"],"pubmed_abstract":["<h4>Purpose</h4>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 (<i>EGFR</i>)-mutated non-small-cell lung cancer (NSCLC).<h4>Methods</h4>This phase II study (ClinicalTrials.gov identifier: NCT04619004) was designed to evaluate HER3-DXd in patients with advanced <i>EGFR-</i>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.<h4>Results</h4>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.<h4>Conclusion</h4>After tumor progression with EGFR TKI therapy and PBC in patients with <i>EGFR</i>-mutated NSCLC, HER3-DXd once every 3 weeks demonstrated clinically meaningful efficacy with durable responses, including in CNS metastases. A phase III trial in <i>EGFR-</i>mutated NSCLC after progression on an EGFR TKI is ongoing (HERTHENA-Lung02; ClinicalTrials.gov identifier: NCT05338970)."],"journal":["Journal of clinical oncology : official journal of the American Society of Clinical Oncology"],"pubmed_title":["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."],"pmcid":["PMC10713116"],"funding_grant_id":["P30 CA008748"],"pubmed_authors":["Johnson ML","Reck M","Yu HA","Goto Y","Yoh K","Felip E","Wu YL","John T","Dong Q","Kozuki T","Patel P","Kim DW","Sellami D","Bironzo P","Smit E","Besse B","Patel J","Chih-Hsin Yang J","Kao S","Sternberg DW","Paz-Ares L","Massarelli E","Janne PA","Lee SH","Hayashi H","Reckamp KL","Shrestha P","Fan PD","Sporchia A"],"additional_accession":[]},"is_claimable":false,"name":"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.","description":"<h4>Purpose</h4>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 (<i>EGFR</i>)-mutated non-small-cell lung cancer (NSCLC).<h4>Methods</h4>This phase II study (ClinicalTrials.gov identifier: NCT04619004) was designed to evaluate HER3-DXd in patients with advanced <i>EGFR-</i>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.<h4>Results</h4>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.<h4>Conclusion</h4>After tumor progression with EGFR TKI therapy and PBC in patients with <i>EGFR</i>-mutated NSCLC, HER3-DXd once every 3 weeks demonstrated clinically meaningful efficacy with durable responses, including in CNS metastases. A phase III trial in <i>EGFR-</i>mutated NSCLC after progression on an EGFR TKI is ongoing (HERTHENA-Lung02; ClinicalTrials.gov identifier: NCT05338970).","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Dec","modification":"2024-11-06T06:58:57.031Z","creation":"2024-11-06T06:58:57.031Z"},"accession":"S-EPMC10713116","cross_references":{"pubmed":["37689979"],"doi":["10.1200/JCO.23.01476"]}}