Study of Trastuzumab Deruxtecan Versus Standard of Care Chemotherapy for HER2-Expressing (IHC 3+/2+) Endometrial Cancer

Официальное название

A Phase 3, Multicenter, Randomized, Open-label Trial of Trastuzumab Deruxtecan Versus Standard of Care Chemotherapy With or Without Radiotherapy as Adjuvant Treatment for HER2-Expressing (IHC 3+/2+) Endometrial Cancer (DESTINY-Endometrial02/ GOG-3122/ ENGOT-en30/GINECO)

Обзор

This study is designed to assess efficacy and safety of T-DXd adjuvant therapy, with or without radiotherapy, post-surgery in anticancer treatment naïve (including neoadjuvant therapy) endometrial cancer with various HER2 expression levels.

Подробное описание

This is a global, multicenter, open-label, phase 3 study to evaluate the efficacy and safety of T-DXd versus SoC chemotherapy with or without radiotherapy as adjuvant treatment in participants with HER2-expressing (IHC 3+/2+) endometrial cancer. Participants will be randomized 1:1 to either T-DXd or SoC chemotherapy. The primary objective will assess disease-free survival as assessed radiographically by BICR or by histopathologic confirmation of disease recurrence per local assessment.

T-DXd (Enhertu®) is a HER2 directed ADC composed of a humanized anti-HER2 IgG1 mAb with the same amino acid sequence as trastuzumab, which includes a plasma-stable, selectively cleavable linker and potent topoisomerase I inhibitor payload (a derivative of exatecan) that leverages the clinically validated DXd ADC technology.

Вмешательства

• Препарат Trastuzumab Deruxtecan
  T-DXd will be administered at a dose of 5.4 mg/kg IV Q3W.
• Препарат Chemotherapy
  Carboplatin AUC 5 or 6 and paclitaxel will be administered at a dose of 175 mg/m2 Q3W, or carboplatin AUC 5 or 6 and paclitaxel 175 mg/m2 Q3W followed by chemoradiotherapy.

Первичные конечные точки

• Disease-Free Survival as Assessed by Blinded Independent Central Review or by Histopathologic Confirmation of Disease Recurrence per Local Assessment [Срок оценки: From randomization to the first documented local regional recurrence, distant metastasis, or death due to any cause, whichever occurs first, up to approximately 51 months]

Вторичные конечные точки (1)

• Overall Survival [Срок оценки: From randomization to the date of death due to any cause, up to approximately 63 months]

Критерии участия

Критерии включения

• Adults ≥18 years at the time the ICF is signed (Please follow local regulatory requirements if the legal age of consent for trial participation is >18 years old)
• Has histologically confirmed diagnosis of epithelial endometrial carcinoma. All histology's are allowed except for sarcomas (carcinosarcomas are allowed).
• Is newly diagnosed FIGO 2023 Stage IIC (including Stage IICmp53abn) or Stage III Note: FIGO 2023 Stage IIC includes disease with aggressive histological types (aggressive histological types are composed of high-grade EECs (grade 3), serous, clear cell, undifferentiated, mixed, mesonephric-like, gastrointestinal mucinous type carcinomas, and carcinosarcomas) with any myometrial involvement. FIGO 2023 Stage III includes disease with local and/or regional spread of the tumor of any histological subtype.
• Has HER2-expression (IHC 3+/2+) per 2016 ASCO-CAP gastric cancer IHC scoring guidelines as confirmed by central laboratory testing.
• Has adequate archived tumor tissue sample (sample from surgery is strongly recommended) available for assessment of HER2 status by central laboratory.

Критерии исключения

• Has uterine mesenchymal tumor such as an endometrial stromal sarcoma, leiomyosarcoma, or other types of pure sarcomas. Adenosarcomas are also not allowed.
• Has recurrent or FIGO 2023 Stage IV
• Has measurable residual tumor after surgery as determined by BICR assessment.
• Is known to have a POLE mutation from an approved and/or validated local test, according to local regulations, if available
• Has a medical history of MI within 6 months before randomization/enrollment, symptomatic CHF (NYHA Class II to IV). Participants with troponin levels above ULN at SCR (as defined by the manufacturer), and without any MI related symptoms should have a cardiologic consultation during SCR Period to rule out MI.
• Has a QTcF prolongation to > 480 msec based on average of the SCR triplicate12-lead ECG. Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder (ie, pulmonary emboli within 3 months of the trial enrollment, severe asthma, severe COPD, restrictive lung disease, pleural effusion, etc.) and any autoimmune, connective tissue, or inflammatory disorder with potential pulmonary involvement (eg, rheumatoid arthritis, Sjogren's syndrome, sarcoidosis, etc.), or prior pneumonectomy.
• Has a history of (noninfectious) ILD/pneumonitis that required corticosteroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at SCR.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 16 центров

• Beijing Cancer Hospital — Пекин
• The First Hospital of Jilin University — Changchun
• West China Second University Hospital, Sichuan University — Чэнду
• Obstetrics and Gynecology Hospital Affiliated to Zhejiang University School of Medicine — Ханчжоу
• Zhejiang Cancer Hospital — Ханчжоу
• Cancer Hospital of Shandong First Medical University — Цзинань
• Linyi Cancer Hospital — Linyi
• Jiangxi Maternal and Child Health Hospital — Nanchang
• … и ещё 8 центров

Япония · 14 центров

• Hyogo Cancer Center — Akashi-shi
• NHO Kyushu Cancer Center — Fukuoka
• Fukushima Medical University Hospital — Fukushima
• Saitama Medical University International Medical Center — Hidaka-shi
• Cancer Institute Hospital of JFCR — Kōtoku
• Kurume University Hospital — Kurume-shi
• Niigata Cancer Center Hospital — Niigata
• Okayama University Hospital — Okayama
• … и ещё 6 центров

США · 10 центров

• Broward Health Medical Center — Fort Lauderdale
• Miami Cancer Institute — Miami
• Mount Sinai Medical Center — Miami Beach
• Parkview Research Center — Fort Wayne
• Trials365 LLC — Shreveport
• FirstHealth of the Carolinas, Inc. — Pinehurst
• University of Cincinnati Physicians Group, LLC — Cincinnati
• Avera Medical Group Gynecologic Oncology Sioux Falls — Sioux Falls
• … и ещё 2 центра

Италия · 6 центров

• Istituto Tumori Giovanni Paolo II IRCCS Ospedale Oncologico Bari — Bari
• Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi IRCCS — Bologna
• Azienda Ospedaliera Universitaria Careggi — Florence
• Presidio Ospedaliero Alessandro Manzoni di Lecco — Lecco
• IEO Istituto Europeo di Oncologia — Milan
• Ospedale Mauriziano Umberto I — Torino

Испания · 6 центров

• Complejo Hospitalario Universitario A Coruña — A Coruña
• Hospital Universitario Virgen de la Arrixaca — El Palmar
• Hospital Universitario Ramon y Cajal — Madrid
• Hospital Universitario 12 de Octubre — Madrid
• Hospital Universitario La Paz — Madrid
• Hospital Universitari Son Espases — Palma de Mallorca

Аргентина · 5 центров

• Hospital Italiano de Buenos Aires — Ciudad Autonoma Buenos Aires
• Sanatorio Allende Cerro — Córdoba
• Centro de Investigaciones Medicas Mar del Plata — Mar del Plata
• Instituto de Oncologia de Rosario — Rosario
• CER San Juan Centro Polivalente de Asistencia e Inv. Clinica — San Juan

Тайвань · 4 центра

• Taichung Veterans General Hospital — Taichung
• National Cheng Kung University Hospital — Tainan
• National Taiwan University Hospital — Taipei
• Taipei Veterans General Hospital — Taipei

Чили · 3 центра

• Biocenter — Concepción
• Centro de Estudios Clinicos SAGA — Santiago
• Centro de Investigaciones Clinicas de la Universidad Catolica — Santiago

Франция · 3 центра

• Centre Francois Baclesse — Caen
• Centre Jean Perrin - CLCC — Clermont-Ferrand
• Institut Claudius Regaud — Toulouse

South Korea · 3 центра

• Keimyung University Dongsan Hospital — Daegu
• Samsung Medical Center — Seoul
• Seoul National University Hospital — Seoul

Германия · 2 центра

• Klinikum Lippe-Detmold — Detmold
• Universitatsklinikum Frankfurt — Frankfurt

Польша · 2 центра

• Szpitale Pomorskie spółka z ograniczoną odpowiedzialnością — Gdynia
• Uniwersytecki Szpital Kliniczny w Poznaniu — Poznan

Португалия · 1 центр

• Hospital da Luz — Lisbon

Идентификаторы

NCT: NCT07022483 · DS8201-854

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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