In this subgroup, the median time to response was 2.6 months (range, 1.2-5.4), and the median duration of response was 6.9 months (95% CI, 3.1-NE). In the cohort of 53 patients with HER3 high metastatic triple negative breast cancer (TNBC), an ORR of 22.6% (95% CI: 12.3-36.2) was observed with patritumab deruxtecan, as assessed by BICR. Patients must have progressed on or after treatment with a third-generation TKI to be included in the trial. "Significant unmet need still remains for the treatment of patients with metastatic breast cancer and new treatment strategies need to be continuously explored," said Ian E. Krop, MD, PhD, Chief Clinical Research Officer, Associate Cancer Center Director for Clinical Research, Yale Cancer Center. FDA Approves Cemiplimab Plus Chemo in Advanced NSCLC, NVL-520 May Stop Tumor Growth, Garner CNS Response in ROS1+ NSCLC and Solid Tumors, Sinoatrial Node Radiation During CRT May Increase Risk of Atrial Fibrillation in SCLC and NSCLC, 2022 ASCO Genitourinary Cancers Symposium Urothelial Cancer Updates, Contemporary Concepts in Hematologic Oncology, Insights from Experts at Mayo Clinic on Translating Evidence to Clinical Practice, Optimizing Outcomes in Patients with HER2+ Metastatic Breast Cancer, Real-World Evidence in NSCLC Guides Clinical Decisions, Targeting NSCLC with Uncommon EGFR Mutations, Nurse Practitioners/Physician's Assistants, Patritumab deruxtecan granted U.S. FDA breakthrough therapy designation in patients with metastatic EGFR-mutated non-small cell lung cancer. From: Clinical Lung Cancer, 2021 Download as PDF About this page Patritumab Patritumab ( INN) is a human monoclonal antibody designed for the treatment of cancer. The primary end point of the dose-expansion portion of the study is the efficacy of patritumab deruxtecan, which will be defined by confirmed ORR per blinded independent central review. Efficacy and safety of patritumab deruxtecan (HER3-DXd) in EGFR inhibitorresistant. [3] It is to be included in a new arm of the I-SPY 2 breast cancer trial. In patients with NSCLC without identified driver genomic alterations, an ORR of 26.9% (95% CI: 11.6-47.8) was observed with patritumab deruxtecan in 26 patients, as assessed by BICR. Daiichi Sankyo is dedicated to creating new modalities and innovative medicines by leveraging our world-class science and technology for our purpose to contribute to the enrichment of quality of life around the world. In addition to our current portfolio of medicines for cancer and cardiovascular disease, Daiichi Sankyo is primarily focused on developing novel therapies for people with cancer as well as other diseases with high unmet medical needs. First preliminary results from one cohort of an ongoing phase 1 trial reported durable responses with patritumab deruxtecan after a median follow-up of 19.7 months (range, 13.8-29.2) in patients with locally advanced or metastatic NSCLC without most frequent EGFR activating mutations (EX19del, L858R, L861Q or G719X) or without identified driver genomic alterations. It is currently being investigated across multiple cancers as both a monotherapy and in combination with other anticancer treatments. The antibody is covalently conjugated, via cysteine residues, through a tumor selective cleavable linker to the payload. Daiichi Sankyo Europe GmbH An ORR of 28.6% (95% CI: 11.3-52.2), as assessed by BICR, was observed with patritumab deruxtecan in 21 patients with advanced NSCLC with identified driver genomic alterations other than EGFR activating mutations. Notably, this is the first breakthrough therapy designation for patritumab deruxtecan. Global/US: ClinicalTrials.gov. +49 (176) 11780822 (mobile) The primary end point is ORR by blinded independent central review. Patritumab deruxtecan (HER3-DXd), a novel HER3 directed antibody drug conjugate, exhibits in vitro activity against breast cancer cells expressing HER3 mutations with and without HER2 overexpression PLoS One. Five patients (10.6%) had confirmed treatment-related ILD as determined by an independent adjudication committee. Partial responses (PRs) were observed in 30.1% of patients and 50.4% of patients had a best overall response (BOR) of stable disease (SD). +1 908 821 7376 (mobile) The dose expansion part of the trial is evaluating patritumab deruxtecan at the RDE (5.6 mg/kg every three weeks) in three cohorts. Daiichi Sankyo. Investor Relations Contact: Additionally, a subgroup of efficacy-evaluable patients who had received prior platinum-based chemotherapy and osimertinib (n = 44) achieved an ORR of 39% (95% CI, 24.4%-54.5%), with 1 patient experiencing a complete response. Efficacy and safety of patritumab deruxtecan (HER3-DXd) in EGFR inhibitor-resistant, EGFR-mutated (EGFRm) non-small cell lung cancer (NSCLC. Daiichi Sankyo Company, Limited. Secondary endpoints include overall response rate, safety, and pharmacokinetics, according to the press release. Extended follow-up data from the dose-escalation portion and cohort 1 of the dose-expansion portion of the study were presented at the 2021 ASCO Annual Meeting, OncClub: Join the Chat on Trending Trials in Cancer, 2023 nominations are open for Giants of Cancer Care, Complimentary print subscription for home or office delivery, In-person and virtual events just for HCPs, Subscribe to our eNewsletter for breaking news and curated content, Patritumab deruxtecan granted U.S. FDA breakthrough therapy designation in patients with metastatic EGFR-mutated non-small cell lung cancer. Treatment-related Grade 3 TEAEs occurred in 120 patients (65.9%) and included neutrophil count decrease, platelet count decrease, white blood cell count decrease, anemia, alanine aminotransferase increase, aspartate aminotransferase increase, decreased appetite, nausea, fatigue, diarrhea, malaise, stomatitis and vomiting. So any degree of expression in the tumor or around the tumor seems to be adequate to have the opportunity to generate an antitumor effect., In December 2021, the FDA granted patritumab deruxtecan a breakthrough therapy designation for the treatment of patients with metastatic or locally advanced NSCLC harboring an EGFR mutation, following disease progression after treatment with a TKI and platinum-based chemotherapy.4, Patritumab deruxtecan is under examination in the phase 1 U31402-A-U102 study (NCT03260491), which enrolled patients with locally advanced or metastatic NSCLC with and without identified driver genomic alterations. Cohort 3 includes patients with NSCLC with EGFR-activating mutations including any histology other than combined small cell and non-small cell lung cancer; patients in Cohort 3 are randomized 1:1 to receive the 5.6 mg/kg RDE regimen (Cohort 3a) or an escalating up-titration regimen of patritumab deruxtecan (Cohort 3b). PRs were observed in 42.9% of patients and 50.0% of patients had a BOR of SD. Accessed January 3, 2021. https://www.businesswire.com/news/home/20211222005517/en, Study: Inhibiting S100A9 Gene in Skin Cells Reduces Severity of Psoriasis, Psoriatic Arthritis, Study: Vitamin C May Improve Efficacy of Dendritic Cell-Derived Anticancer Cell Therapies, Review Results Link HPV Infections With Pregnancy Outcomes, https://www.businesswire.com/news/home/20211222005517/en. The approval of an agent that we can use for all patients, regardless of subsequent genomic status, will be clinically quite useful and meaningful to our patients and we hope would improve outcomes.. It is designed to target and help deliver chemotherapy to cancer cells that express HER3 on the surface of tumor cells. doi: 10.1371/journal.pone.0267027. HER3 is a member of the EGFR family of receptor tyrosine kinases, which are associated with aberrant cell proliferation and survival.3 It is estimated that about 83% of all NSCLC tumors express the HER3 protein. 8 Siegel R, et al. Patritumab deruxtecan is a potential first-in-class HER3 directed antibody drug conjugate (ADC) discovered and being developed by Daiichi Sankyo. News release. Patritumab Deruxtecan Granted US FDA Breakthrough Therapy Designation in Patients with Metastatic EGFR-Mutated Non-Small Cell Lung Cancer. Patients were heavily pre-treated, and those with HR positive/HER2 negative metastatic breast cancer had received a median of six (range, 2-13) prior lines of therapy in the advanced setting; patients with metastatic TNBC had received a median of two (range, 1-13) prior therapies; and patients with HER2 positive breast cancer had received a median of 5.5 (range, 2-11) prior therapies. Cohort 1 includes patients with locally advanced or metastatic EGFR-mutated NSCLC who experienced disease progression after taking one or more EGFR TKIs and one or more platinum-based chemotherapy regimens. The global, multicenter, open label, two-part phase 1 trial is evaluating patritumab deruxtecan in previously treated patients with metastatic or unresectable NSCLC. 2021; 10.3322/caac.21660. Patritumab deruxtecan is comprised of a fully human anti-ERBB3 (HER3) immunoglobulin G1 monoclonal antibody attached to a topoisomerase I inhibitor payload via a stable tetrapeptide-based cleavable linker. 2 National Cancer Institute. 2 Clarke DriveSuite 100Cranbury, NJ 08512. 2022 MJH Life Sciences and Pharmacy Times Pharmacy Practice News and Expert Insights. Patritumab deruxtecan will be given intravenously every 3 weeks. Responses with patritumab deruxtecan were seen in patients with a broad range of driver genomic alterations, including KRAS/NRAS mutations and ALK fusions. Serious treatment-related AEs were reported in 21% of efficacy-evaluable patients.5. These data also reinforce the potential emerging role of targeting HER3 with an antibody drug conjugate to overcome resistance to standard of care treatment in patients with HER3 expressing metastatic breast cancer as well as in patients with advanced non-small cell lung cancer without EGFR activating mutations, which we plan to continue to explore in additional trials., HER3 Expressing Metastatic Breast Cancer Results. The breakthrough therapy designation for patritumab deruxtecan acknowledges the need for new treatment approaches to overcome resistance and improve survival in patients with metastatic TKI-resistant, EGFR-mutated [NSCLC], Ken Takeshita, MD, global head of R&D at Daiichi Sankyo, said in a press release. News release. The agent also demonstrated comparable efficacy benefit in 44 patients who had received prior osimertinib (Tagrisso) and platinum-based chemotherapy, with a confirmed ORR of 39% (95% CI, 24%-55%), a DCR of 68% (95% CI, 52%-81%), and a median PFS of 8.2 months (95% CI, 4.0not evaluable [NE]). Lung Fact Sheet. Pooled analysis from a three-part, first-in-human phase 1/2 trial evaluating patritumab deruxtecan (n=182) showed clinically meaningful and durable responses after a median follow-up of 31.9 months (range, 15-56) in patients with three different subtypes of HER3 expressing metastatic breast cancer, including HR positive/HER2 negative, triple negative and HER2 positive disease. Median DOR was 5.9 months (95% CI: 3.0-8.4). Safety and efficacy have not been established. 7 American Cancer Society. 2018;12(1):355. Designed using Daiichi Sankyos proprietary DXd ADC technology, patritumab deruxtecan is comprised of a fully human anti-HER3 IgG1 monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers. To ensure the most secure and best overall experience on our website we recommend the latest versions of, Internet Explorer is no longer supported. Prescribing information. Regarding safety, all patients treated at the recommended dose experienced a treatment-emergent adverse effect (TEAE). Daiichi-Sankyo. Mok TK, Wu YL, Ahn MJ, et al; AURA3 Investigators. Patritumab deruxtecan is comprised of a human anti-HER3 antibody attached to a topoisomerase I inhibitor payload by a tetrapeptide-based linker. kawase.masashi.a2@daiichisankyo.co.jp 2019. 2 Clarke DriveSuite 100Cranbury, NJ 08512. The agent also elicited a disease control rate (DCR) of 72% (59%-83%) and induced a median progression-free survival (PFS) of 8.2 months (95% CI, 4.4-8.3). Median progression-free survival (PFS) was 7.4 months (95% CI: 4.7-8.4) and median overall survival (OS) was 14.6 months (95% CI: 11.3-19.5). The trial enrolled patients at multiple sites in Asia, Europe and North America. December 23, 2021. Treatment-emergent adverse events (TEAEs) associated with treatment discontinuation was 9.9%. The median time to response was 2.6 months (95% CI, 1.2-5.4).5. All rights reserved. The DCR was 68% (95% CI, 52.4%-81.4%) and the median DOR was 7.0 months (95% CI, 3.1-NE). Content Developed Independently by OncLive. The dose expansion part of the study is evaluating patritumab deruxtecan at 5.6 mg/kg every 3 weeks in 3 cohorts. All rights reserved. Patients in the dose escalation and dose finding parts of the trial must have received six or fewer prior chemotherapy regimens, at least two of which were administered for treatment of advanced/unresectable metastatic disease, and at least one prior chemotherapeutic regimen must have included a taxane, administered in the neoadjuvant, adjuvant or advanced setting. 9 Walters S, et al. Patritumab-deruxtecan (HER3-DXd) is an ADC consisting of the fully-human anti-HER3 monoclonal antibody patritumab, a cleavable tetrapeptide-based linker, and the topoisomerase I inhibitor payload DXd with a DAR of 8 (Table 1). Approximately 25% to 30% of lung cancers have an EGFR-activating mutation, including approximately 83% of all NSCLC tumors. Grade 3 or higher TEAEs that occurred in at least 5% of patients included decreased platelet count, decreased neutrophil count, fatigue, anemia, dyspnea, febrile neutropenia, hypoxia, decreased white blood cell count, hypokalemia, and decreased lymphocyte count. Cohort 1 includes patients with locally advanced or metastatic EGFR-mutated NSCLC with disease progression following at least 1 EGFR TKI and platinum-based chemotherapy regimen. A confirmed objective response rate (ORR) of 30.1% (95% CI: 21.8-39.4) was observed with patritumab deruxtecan in the cohort of 113 patients with HER3 high or HER3 low, HR positive/HER2 negative metastatic breast cancer, as assessed by blinded independent central review (BICR). Investigators are actively recruiting patients and the trial has an estimated completion date of August 2026.8,9, Right now, our go-to first-line agent for EGFR-mutant lung cancer is osimertinib, Rotow said. Cohort 2 includes patients with squamous or nonsquamous NSCLC without EGFR-activating mutations following platinum-based chemotherapy and a PD-1/PD-L1based regimen. CA Cancer J Clin. Among the 25 patients with a history of brain metastases, the confirmed ORR with patritumab deruxtecan was 32% (95% CI, 15%-54%), with a median PFS of 8.2 months (95% CI, 4.0-NE). Accessed September 21, 2022. bit.ly/3SkV5Iv. In December 2021, the FDA granted a breakthrough therapy designation to patritumab deruxtecan for the treatment of patients with metastatic or locally advanced EGFR-mutated non-small cell lung cancer (NSCLC) with disease progression on or after treatment with a third-generation TKI and platinum-based therapies. Cohort 3 includes patients with NSCLC with EGFR-activating mutations including any histology other than combined small cell lung cancer and NSCLC; patients in cohort 3 will be randomized 1:1 to receive 5.6 mg/kg of patritumab deruxtecan (cohort 3a) or an escalated regimen of patritumab deruxtecan (cohort 3b). Accessed May 2022. In December 2021, the FDA granted patritumab deruxtecan a breakthrough therapy designation for the treatment of patients with metastatic or locally advanced NSCLC harboring an EGFR mutation,. In the dose-escalation portion of the trial, patients received intravenous patritumab deruxtecan once every 3 weeks at a dose of 3.2 mg/kg (n = 4), 4.8 mg/kg (n = 15), 5.6 mg/kg (n = 12), or 6.4 mg/kg (n = 5). 3 Investigators evaluated a . ErbB3 (HER3), a member of the HER family, is overexpressed in various cancers and plays an important role in cell proliferation and survival. The Breakthrough Therapy Designation for patritumab deruxtecan acknowledges the need for new treatment approaches to overcome resistance and improve survival in patients with metastatic [tyrosine kinase inhibitor]-resistant, EGFR-mutated non-small cell lung cancer, said Ken Takeshita, MD, global head of research and development at Daiichi Sankyo, in the press release. 3 Mishra R, et al. Daiichi Sankyo, Inc. Finally, cohort 3 includes patients with NSCLC with EGFR-activating mutations including any histology other than combined small cell and NSCLC. simone.dowe@daiichi-sankyo.eu PRs were observed in 22.6% of patients and 56.6% of patients had a BOR of SD. Overall, 12 patients (6.6%) had confirmed treatment-related interstitial lung disease (ILD) or pneumonitis as determined by an independent adjudication committee. The dose finding part of the trial assessed the safety and efficacy of patritumab deruxtecan at selected dosing levels to determine the recommended dose for expansion. December 23, 2021. All patients included in the analysis had received prior EGFR TKI therapy. Accordingly, patritumab deruxtecan [HER3-Dxd; an antibody-drug conjugate (ADC) consisting of a HER3 antibody and topoisomerase I inhibitor payload via tetrapeptide-based cleavable linker] has been developed to target previously regarded as "undruggable" catalytically defective receptor tyrosine kinase. 1 Patritumab deruxtecan is a potential first-in-class HER3 directed antibody drug conjugate (ADC) discovered and being developed by Daiichi Sankyo. 11 Scharpenseel H, et al. Thorax. Six patients had PRs and 10 patients had a best overall response of stable disease. Accessed May 2022. News release. Simone Jendsch-Dowe The evaluation was done in pooled patients with EGFR-mutated disease, and the median follow-up was 10.2 months (range, 5.2-19.9). In the current study, antitumor activity of patritumab deruxtecan (HER3-DXd), a HER3 directed antibody drug conjugate, was evaluated in . In December 2021, patritumab deruxtecan was granted Breakthrough Therapy Designation (BTD) by the U.S. Food and Drug Administration (FDA) for the treatment of patients with metastatic or locally advanced EGFR-mutated NSCLC with disease progression on or after treatment with a third-generation TKI and platinum-based therapies. Common TEAEs of grade 3 or greater included thrombocytopenia (30%), neutropenia (19%), and fatigue (14%). Seven percent of patients (n = 4) experienced fatal TEAEs: these included disease progression (n = 2), respiratory failure (n = 2), and shock (n = 1). BusinessWire; December 23, 2021. The rate of adjudicated treatment-related interstitial lung disease (ILD) was 5%, none of which were grade 4 or 5. Cancer Stat Facts: Lung and Bronchus. Patritumab deruxtecan (HER3-DXd, U3-1402) is an antibody-drug conjugate (ADC) comprising an anti-HER3 mAb linked to a topoisomerase I inhibitor that is in clinical development for patients with NSCLC, metastatic breast cancer, and colorectal cancer. International Agency for Research on Cancer. 5 Sung H, et al. Eligible participants must have disease with either an exon 19 deletion or L858R mutation. Jnne PA, Baik C, Su WC, et al. The phase 1 study was comprised of a dose-escalation and dose-expansion phase. For more information, visit ClinicalTrials.gov. The global, open-label, three-part phase 1/2 trial is evaluating the safety and efficacy of patritumab deruxtecan in patients with HER3 expressing advanced/unresectable metastatic breast cancer who are refractory or intolerant to standard treatment, or for whom no standard treatment is available. Jun 15, 2021 Patritumab deruxtecan (HER3-DXd), an antibody drug conjugate consisting of a monoclonal antibody to HER3 attached to a topoisomerase I, demonstrates anti-tumour activity across various EGFR TKI resistance mechanisms in heavily pretreated, metastatic/locally advanced, EGFR-mutated non-small cell lung cancer (NSCLC). Patritumab deruxtecan is currently being evaluated as both a monotherapy and in combination with other anticancer therapies. Interestingly, for this ADC, it does not look like there is a strong correlation between the level of HER3 and response to the ADC. Japan: The population was heavily pretreated, with a median of 4 (range, 1-9) prior lines of therapy. All rights reserved. 2013;68:551-564. Accessed January 3, 2022. https://bit.ly/3qECNWu, Jnne PA, Baik CS, Su W-C, et al. Authors We are proud that the FDA has once again recognized our innovative science and technology and we look forward to bringing this potential first-in-class HER3 directed antibody drug conjugate to patients with this specific type of lung cancer as quickly as possible.. Listing a study does not mean it has been evaluated by the U.S. Federal Government. For many patients, the genomic mechanism of resistance is not clear., Most patients with advanced NSCLC harboring an EGFR mutation will experience disease progression after treatment with an EGFR-directed tyrosine kinase inhibitor (TKI) in an early line of therapy. Secondary end points include OS, ORR, clinical benefit rate, and DCR. Updated on September 21, 2022. For patients who are receiving first-line osimertinib [Tagrisso], the challenge of how to manage resistance in the clinical setting remains difficult. 2022 May 3;17 (5):e0267027. The primary end point of the study is PFS by blinded independent central review.
Premier Health Benefits, Yugioh Master Duel Budget Cards, Campus Edge Wilmington, Hades Elysium Boss Chamber, Danger Jackalope Master Duel Mate, The Langdon Apartments, Apartments For Rent In Glen Rock, Pa, Great Physician Hour Today, Houses For Sale In Irene View Estate, Weighted Average Method Process Costing, Ana Premium Economy 787-9, Wacom Art Pen Compatibility, Jonathan Segal Architect,