Enhertu aprobado en EE. UU. para tumores sólidos HER2+
Renk AG
n / a
07:46 20/03/24
08 de abril de 2024
Enhertu approved in the US as first tumour-agnostic HER2-directed therapy
for previously treated patients with metastatic HER2-positive solid tumours
Based on three Phase II trials of AstraZeneca and Daiichi Sankyo's Enhertu which showed clinically meaningful responses across a broad range of tumours
Enhertu now has five approved indications with the latest in HER2-expressing
(IHC 3+) metastatic cancers
AstraZeneca y Daiichi Sankyo Enhertu (trastuzumab deruxtecan) has been approved in the US for the treatment of adult patients with unresectable or metastatic HER2-positive (IHC 3+) solid tumours who have received prior systemic treatment and have no satisfactory alternative treatment options.
Esta indicación está aprobada bajo aprobación acelerada basada en la tasa de respuesta objetiva (ORR) y la duración de la respuesta (DoR). La continuación de la aprobación para esta indicación puede depender de la verificación y descripción del beneficio clínico en un ensayo de confirmación.
Enhertu is a specifically engineered HER2-directed antibody drug conjugate (ADC) discovered by Daiichi Sankyo and being jointly developed and commercialised by AstraZeneca and Daiichi Sankyo.
The first tumour-agnostic approval of a HER2-directed therapy and ADC by the Food and Drug Administration (FDA) was based on results from the subgroup of patients with HER2-positive IHC 3+ tumours in each of the DESTINO-PanTumor02, DESTINO-Pulmón01 y DESTINY-CRC02 Phase II trials.
Funda Meric-Bernstam, MD, Chair of Investigational Cancer Therapeutics at The University of Texas MD Anderson Cancer Center, US, said: "Until the approval of trastuzumab deruxtecan, patients with metastatic HER2-positive solid tumours have had limited treatment options. Based on the clinically meaningful response rates seen across clinical trials, this tumour-agnostic approval means that patients may now be treated with a HER2-directed medicine."
Dave Fredrickson, Executive Vice President, Oncology Business Unit, AstraZeneca, said: "As the first antibody drug conjugate to be granted a tumour-agnostic indication, Enhertu is truly delivering on its potential across metastatic HER2-targetable tumours. This approval also elevates the importance of testing for biomarkers, including HER2, across a broad range of tumours to ensure these patients with advanced cancer who have few options know whether a targeted medicine might be right for them."
Ken Keller, Global Head of Oncology Business, and President and CEO, Daiichi Sankyo, Inc., said: "This fifth indication in the US is a significant milestone as eligible patients with previously treated metastatic HER2-positive solid tumours may now be treated with Enhertu. The accelerated approval by the FDA for this tumour-agnostic indication is based on the clinically meaningful efficacy seen with Enhertu across numerous types of metastatic cancers."
In the DESTINY-PanTumor02 Phase II trial, patients with centrally or locally assessed HER2-positive (IHC 3+) solid tumours including either biliary tract, bladder, cervical, endometrial, ovarian, pancreatic or other tumours treated with Enhertu showed a confirmed ORR of 51.4% (95% confidence interval [CI] 41.7-61.0) and a median DoR range of 19.4 months (range 1.3-27.9+ [+ denotes ongoing responses at data cutoff]). In DESTINY-Lung01, patients with centrally confirmed HER2-positive (IHC 3+) non-small cell lung cancer (NSCLC) treated with Enhertu showed a confirmed ORR of 52.9% (95% CI 27.8-77.0) and median DoR range of 6.9 months (range 4.0-11.7+). A confirmed ORR of 46.9% (95% CI 34.3-59.8) and median DoR range of 5.5 months (range 1.3+-9.7+) was seen in patients with centrally confirmed HER2-positive (IHC 3+) colorectal cancer in the DESTINY-CRC02 trial.
La seguridad de Enhertu was evaluated in 347 patients with unresectable or metastatic HER2-positive (IHC 3+) solid tumours in the DESTINY-Breast01, DESTINY-PanTumor02, DESTINY-Lung01 and DESTINY-CRC02 trials. The safety profile observed across the trials was consistent with previous clinical trials of Enhertu with no new safety concerns identified.
Con base en estos resultados, fam-trastuzumab deruxtecan-nxki (Enhertu) has been included in the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) as a treatment option for multiple metastatic tumours. See NCCN Guidelines® for detailed recommendations.1
This approval was granted under the FDA's Real-Time Oncology Review programme after securing Revisión prioritaria y Designación de Terapia Avanzada para Enhertu en los EE.UU. en este entorno.
The US regulatory submission was reviewed under Project Orbis, which provides a framework for concurrent submission and review of oncology medicines among participating international partners. As part of Project Orbis, Enhertu is also under regulatory review for the same indication by regulatory authorities in Australia, Brazil and Singapore.
Consideraciones financieras
Ventas de Enhertu en los EE. UU. son reconocidos por Daiichi Sankyo. AstraZeneca reporta su participación en el margen de utilidad bruta de Enhertu sales in the US as alliance revenue in the Company's financial statements.
En el Anuncio del 2019 de marzo de la colaboracion
Notas
HER2 expression in solid tumours
HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of various tissue cells throughout the body and is involved in normal cell growth.2,3 In some cancers, HER2 expression is amplified or the cells have activating mutations.2,4 HER2 protein overexpression may occur as a result of HER2 gene amplification and is often associated with aggressive disease and poor prognosis.5
HER2-directed therapies have been used to treat breast, gastric, lung and colorectal cancers for a number of years.3,6,7 Although HER2 is expressed in solid tumour types including biliary tract, bladder, cervical, endometrial, ovarian and pancreatic cancers, testing is not routinely performed in these additional tumour types and as a result, available literature is limited.4 In these solid tumours, HER2-positive expression, classified as immunohistochemistry (IHC) 3+, has been observed at rates from 1% to 28%.8,9 Approximately 1% to 5% of patients with NSCLC have tumours with HER2 overexpression (IHC 3+), however, the levels of protein expression reported vary in the literature.8,10 Approximately 1% to 4% of patients with metastatic colorectal cancer have tumours which are HER2 overexpressing (IHC 3+).8,11,12
DESTINO-PanTumor02
DESTINY-PanTumor02 is a global, multicentre, multi-cohort, open-label Phase II trial evaluating the efficacy and safety of Enhertu (5.4mg/kg) for the treatment of previously treated HER2-expressing tumours, including biliary tract cancer, bladder cancer, cervical cancer, endometrial cancer, ovarian cancer, pancreatic cancer or other tumours.
The primary efficacy endpoint of DESTINY-PanTumor02 is confirmed ORR as assessed by investigator. Secondary endpoints include DoR, disease control rate (DCR), progression-free survival (PFS), overall survival (OS), safety, tolerability and pharmacokinetics.
DESTINY-PanTumor02 has enrolled 267 patients, including 111 HER2-positive (IHC 3+) adult patients, at multiple sites in Asia, Europe and North America, and is to be expanded to recruit more patients with metastatic HER2-positive IHC 1+, IHC 2+ and IHC 3+ tumours. For more information about the trial, visit ClinicalTrials.gov.
DESTINO-Pulmón01
DESTINY-Lung01 is a global Phase II, open-label, two-cohort trial evaluating the efficacy and safety of Enhertu (5.4mg/kg or 6.4mg/kg) in patients with HER2-mutant (cohort 2, n=91) or HER2-overexpressing (defined as IHC 3+ or IHC 2+) [cohort 1 and 1a, n=90] unresectable or metastatic non-squamous NSCLC who had progressed after one or more systemic therapies.
The primary endpoint is confirmed ORR by independent central review. Key secondary endpoints include DoR, DCR, PFS, OS and safety.
DESTINY-Lung01 enrolled 181 patients, including 17 HER2-positive (IHC 3+) adult patients, at multiple sites, including Asia, Europe and North America. For more information about the trial, visit ClinicalTrials.gov.
DESTINY-CRC02
DESTINY-CRC02 is a global, randomised, two arm, parallel, multicentre Phase II trial evaluating the efficacy and safety of two doses (5.4mg/kg or 6.4mg/kg) of Enhertu in patients with locally advanced, unresectable or metastatic HER2-positive colorectal cancer of BRAF wild-type, RAS wild-type or RAS mutant tumour types previously treated with standard therapy.
The trial was conducted in two stages. In the first stage, patients (n=80) were randomised 1:1 to receive either 5.4mg/kg or 6.4mg/kg of Enhertu. In the second stage, additional patients (n=42) were enrolled in the 5.4mg/kg arm.
The primary endpoint is confirmed ORR as assessed by blinded independent central review. Secondary endpoints include DoR, DCR, investigator-assessed confirmed ORR, clinical benefit ratio, PFS, OS and safety.
DESTINY-CRC02 enrolled 122 patients, including 64 HER2-positive (IHC 3+) adult patients, at multiple sites in Asia, Europe and North America. For more information about the trial, visit ClinicalTrials.gov.
DESTINO-mama01
DESTINY-Breast01 is a global, single-arm, open-label, two-part multi-centre Phase II trial evaluating the safety and efficacy of Enhertu in patients with HER2-positive unresectable and/or metastatic breast cancer previously treated with trastuzumab emtansine (T-DM1).
The primary endpoint of the trial is ORR, as determined by independent central review. Secondary objectives include DoR, DCR, clinical benefit rate, PFS and OS.
DESTINY-Breast01 inscribió a 253 pacientes en múltiples sitios en Asia, Europa y América del Norte. Para obtener más información sobre el ensayo, visite ClinicalTrials.gov.
Enhertu
Enhertu es un ADC dirigido por HER2. Diseñado con la tecnología patentada DXd ADC de Daiichi Sankyo, Enhertu es el ADC líder en la cartera de oncología de Daiichi Sankyo y el programa más avanzado en la plataforma científica ADC de AstraZeneca. Enhertu consists of a HER2 monoclonal antibody attached to a number of topoisomerase I inhibitor payloads, (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers.
Enhertu (5.4mg/kg) is approved in more than 60 countries for the treatment of adult patients with unresectable or metastatic HER2-positive (IHC 3+ or in situ hybridization [ISH]+) breast cancer who have received a (or one or more) prior anti-HER2-based regimen, either in the metastatic setting or in the neoadjuvant or adjuvant setting, and have developed disease recurrence during or within six months of completing therapy based on the results from the DESTINY-Breast03 trial.
Enhertu (5.4mg/kg) is approved in more than 55 countries for the treatment of adult patients with unresectable or metastatic HER2-low (IHC 1+ or IHC 2+ISH-) breast cancer who have received a prior systemic therapy in the metastatic setting or developed disease recurrence during or within six months of completing adjuvant chemotherapy based on the results from the DESTINY-Breast04 trial.
Enhertu (5.4mg/kg) is approved in more than 35 countries worldwide for the treatment of adult patients with unresectable or metastatic non-small cell lung cancer whose tumours have activating HER2 (ERBB2) mutations, as detected by a locally or regionally-approved test, and who have received a prior systemic therapy based on the results from the DESTINY-Lung02 trial. Continued approval in the US for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
Enhertu (6.4mg/kg) is approved in more than 45 countries for the treatment of adult patients with locally advanced or metastatic HER2-positive (IHC 3+ or IHC 2+/ISH+) gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen based on the results from the DESTINY-Gastric01 trial and/or DESTINY-Gastric02 trial.
Enhertu (5.4 mg/kg) is approved in the US for the treatment of adult patients with unresectable or metastatic HER2-positive (IHC 3+) solid tumours who have received prior systemic treatment and have no satisfactory alternative treatment options based on the results from the DESTINY-PanTumor02, DESTINY-Lung01 and DESTINY-CRC02 trials. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
Enhertu programa de desarrollo
Se está llevando a cabo un programa integral de desarrollo clínico a nivel mundial, que evalúa la eficacia y seguridad de Enhertu monoterapia en múltiples cánceres atacables para HER2. También se están realizando ensayos en combinación con otros tratamientos contra el cáncer, como la inmunoterapia.
Colaboración con Daiichi Sankyo
Daiichi Sankyo Company, Limited (TSE: 4568) [referida como Daiichi Sankyo] y AstraZeneca iniciaron una colaboración global para desarrollar y comercializar conjuntamente Enhertu (un ADC dirigido por HER2) en Marzo 2019, y datopotamab deruxtecan (DS-1062; un ADC dirigido por TROP2) en Julio 2020, excepto en Japón, donde Daiichi Sankyo mantiene los derechos exclusivos. Daiichi Sankyo es responsable de la fabricación y el suministro de Enhertu y datopotamab deruxtecan.
AstraZeneca en oncología
AstraZeneca está liderando una revolución en oncología con la ambición de proporcionar curas para el cáncer en todas sus formas, siguiendo la ciencia para comprender el cáncer y todas sus complejidades para descubrir, desarrollar y entregar medicamentos que cambian la vida de los pacientes.
El enfoque de la Compañía está en algunos de los cánceres más desafiantes. Es a través de la innovación persistente que AstraZeneca ha construido una de las carteras y proyectos más diversos de la industria, con el potencial de catalizar cambios en la práctica de la medicina y transformar la experiencia del paciente.
AstraZeneca tiene la visión de redefinir la atención del cáncer y, algún día, eliminar el cáncer como causa de muerte.
AstraZeneca
AstraZeneca (LSE/STO/Nasdaq: AZN) es una compañía biofarmacéutica global, liderada por la ciencia, que se enfoca en el descubrimiento, desarrollo y comercialización de medicamentos recetados en Oncología, Enfermedades raras y Biofarmacéuticos, incluidos Cardiovascular, Renal y Metabolismo y Respiratorio. & Inmunología. Con sede en Cambridge, Reino Unido, AstraZeneca opera en más de 100 países y sus medicamentos innovadores son utilizados por millones de pacientes en todo el mundo. Visite a astrazeneca.com and follow the Company on Social Media @AstraZeneca.
Contacto
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Referencias
1. Referenced with permission from the NCCN Guidelines. © National Comprehensive Cancer Network® 2024. All rights reserved. Accessed March 2024. To view the most recent and complete version of the guidelines, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.
2. ASCO. Breast Cancer. Available at: https://www.cancer.net/sites/cancer.net/files/asco_answers_guide_breast.pdf. Consultado en abril de 2024.
3. Iqbal N, et al. Human Epidermal Growth Factor Receptor 2 (HER2) in Cancers: Overexpression and Therapeutic Implications. Mol Biol Int. 2014; 852748.
4. Omar N, et al. HER2-an emerging biomarker in non-breast and non-gastric cancers. Patogenesia. 2015;2(3):1-9.
5. Pillai R, et al. HER2 mutations in lung adenocarcinomas: A report from the Lung Cancer Mutation Consortium. Cáncer. 2017;1;123(21): 4099-4105.
6. National Cancer Institute. Enhertu Marks First Targeted Therapy for HER2-Mutant Lung Cancer. Disponible en: https://www.cancer.gov/news-events/cancer-currents-blog/2022/fda-lung-cancer-enhertu-her2. Accessed April 2024.
7. Siena S, et al. Targeting the Human Epidermal Growth Factor Receptor 2 (HER2) Oncogene in Colorectal Cancer. ann oncol. 2018 mayo; 29 (5): 1108-1119.
8. Yan M, et al. HER2 expression status in diverse cancers: review of results from 37,992 patients. Cáncer Metástasis Rev. 2015 Mar;34(1):157-64.
9. Buza N, et al. Toward standard HER2 testing of endometrial serous carcinoma: 4-year experience at a large academic center and recommendations for clinical practice. Patología moderna. 2013 Dec;26(12):1605-12.
10. Zinner R, et al. Trastuzumab in combination with cisplatin and gemcitabine in patients with Her2-overexpressing, untreated, advanced non-small cell lung cancer: report of a phase II trial and findings regarding optimal identification of patients with Her2-overexpressing disease. Cáncer de Pulmón. 2004; Apr;44(1):99-110.
11. Cecchi F, et al. The HORIZON III retrospective exploratory analysis: HER2 expression amplification in colorectal cancer. J Clin Oncol. 2023;Jan;41(4).
12. Valtora E, et al. Assessment of a HER2 scoring system for colorectal cancer: results from a validation study. mod pathol. 2015 Nov;28(11):1481-91.
Adrián Kemp
Secretaria de Empresa
AstraZenecaPLC
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