A Study of Ifinatamab Deruxtecan Versus Treatment of Physician's Choice in Subjects With Relapsed Small Cell Lung Cancer

Официальное название

A Phase 3, Multicenter, Randomized, Open-label Study of Ifinatamab Deruxtecan (I-DXd), a B7-H3 Antibody Drug Conjugate (ADC), Versus Treatment of Physician's Choice (TPC) in Subjects With Relapsed Small Cell Lung Cancer (SCLC) (IDeate-Lung02)

Обзор

This study is designed to compare the efficacy and safety of I-DXd with treatment of physician's choice in participants with relapsed small cell lung cancer (SCLC).

Подробное описание

The primary objective of this study is to assess whether treatment with I-DXd prolongs overall survival (OS) compared with treatment of physician's choice among participants with relapsed SCLC.

The secondary objectives of the study are to further evaluate the efficacy/safety of I-DXd, health economics and outcome research measures (including patient reported outcomes), immunogenicity of I-DXd, B7-H3 protein expression, and characterize the pharmacokinetics of I-DXd.

Вмешательства

• Препарат Ifinatamab deruxtecan
  12 mg/kg intravenous dose on Day 1 of each 21-day cycle
• Препарат Topotecan
  Topotecan will be administered per local standard-of-care (SoC)
• Препарат Amrubicin
  Amrubicin will be administered per local SoC
• Препарат Lurbinectedin
  Lurbinectedin will be administered per local SoC

Первичные конечные точки

• Overall Survival (OS) [Срок оценки: From the date of randomization to the date of death due to any cause, up to approximately 3.7 years]

Вторичные конечные точки (12)

• Objective Response (OR) Assessed by Blinded Independent Central Review (BICR) Per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1) [Срок оценки: Baseline up until documented progressive disease, death, lost to follow-up, or withdrawal by the participant, up to approximately 3.7 years]
• Number of Participants With OR Assessed by Investigator Per RECIST v1.1 [Срок оценки: Baseline up until documented progressive disease, death, lost to follow-up, or withdrawal by the participant, up to approximately 3.7 years]
• Progression-free Survival (PFS) as Assessed by BICR and Investigator [Срок оценки: Baseline up until documented progressive disease, death, lost to follow-up, or withdrawal by the participant, up to approximately 3.7 years]
• Duration of Response (DoR) as Assessed by BICR and Investigator [Срок оценки: From the date of first documentation of BOR (CR or PR) to the first documentation of objective progression or to death due to any cause, whichever occurs first, up to approximately 3.7 years]
• Disease Control as Assessed by BICR and Investigator [Срок оценки: Baseline up until documented progressive disease, death, lost to follow-up, or withdrawal by the participant, up to approximately 3.7 years]
• Time to Response (TTR) as Assessed by BICR and Investigator [Срок оценки: From the start date of study drug to the date of the first documentation of response (CR or PR) that is subsequently confirmed, up to approximately 3.7 years]
• Change from Baseline in The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-C30 [Срок оценки: Baseline up to 3.7 years]
• Change from Baseline in The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Lung Cancer 29 (EORTC QLQ-LC29) [Срок оценки: Baseline up to 3.7 years]
• Number of Participants With Treatment-emergent Adverse Events (TEAEs) [Срок оценки: Up to 3.7 years]
• Percentage of Participants Who are Anti-Drug Antibody (ADA)-Positive at Any Time (Baseline and Post-baseline) and Who Have a Treatment-emergent Anti-Drug Antibody [Срок оценки: Baseline up to 3.7 years]
• Pharmacokinetic Parameter Maximum Concentration (Cmax) for I-DXd, Total Anti-B7-H3 Antibody, and MAAA-1181a [Срок оценки: Cycle 1 before infusion (BI), end of infusion EOI), and 3, 6, 24, 72, 168, 336 and 504 hours (hrs) post dose; Cycle 2 BI and EOI; Cycle 3 BI, EOI and 6 hrs post dose; Cycles 4, 5, and every 2 cycles thereafter up to 3.7 years BI (each cycle is 21 days)]
• Pharmacokinetic Parameter Time to Maximum Concentration (Tmax) for I-DXd, Total Anti-B7-H3 Antibody, and MAAA-1181a [Срок оценки: Cycle 1 before infusion (BI), end of infusion EOI), and 3, 6, 24, 72, 168, 336 and 504 hours (hrs) post dose; Cycle 2 BI and EOI; Cycle 3 BI, EOI and 6 hrs post dose; Cycles 4, 5 and every 2 cycles thereafter up to 3.7 years BI (each cycle is 21 days)]

Критерии участия

Критерии включения

Participants must meet all the following criteria to be eligible for randomization into the study:

• Sign and date the informed consent form (ICF) prior to the start of any study-specific qualification procedures.
• Adults greater than or equal to (≥)18 years or the minimum legal adult age (whichever is greater) at the time the ICF is signed.
• Has histologically or cytologically documented extensive-stage small cell lung cancer (ES-SCLC).
• The participant must provide adequate baseline tumor samples with sufficient quantity and quality of tumor tissue content.
• Has received prior therapy with only one prior platinum-based line as systemic therapy for SCLC with at least 2 cycles of therapy and a chemotherapy free-interval \[CTFI\] (duration from stop date of the platinum agent in 1L therapy to radiological PD) of ≥30 days.
• Has at least 1 measurable lesion according to RECIST v1.1 as assessed by the investigator.
• Has documentation of radiological disease progression on or after the most recent systemic therapy.
• Has ECOG PS of less than or equal to (≤)1 within 7 days prior to Cycle 1 Day 1 (C1D1).
• Participants with brain metastasis/leptomeningeal disease are eligible if protocol specified criteria are met.

Критерии исключения

Participants who meet any of the following criteria will be disqualified from entering the study:

• Has received prior treatment with orlotamab, enoblituzumab, or other B7 homologue 3 (B7-H3) targeted agents, including I-DXd.
• Prior discontinuation of an antibody drug conjugate (ADC) that consists of an exatecan derivative (eg, trastuzumab deruxtecan) due to treatment-related toxicities.
• Has received any of the comparators used in this study or any topoisomerase I inhibitor.
• Has inadequate washout period before randomization as specified in the protocol.
• Has any of the following conditions within the past 6 months: cerebrovascular accident, transient ischemic attack, or another arterial thromboembolic event.
• Has uncontrolled or significant cardiovascular (CV) disease.
• Has clinically significant corneal disease.
• All of the following indicators of interstitial lung disease (ILD)/pneumonitis are excluded:

• Any history of ILD/pneumonitis irrespective of steroid use, except for a history of radiation pneumonitis that did not require steroids.
• Current diagnosis of ILD.
• Clinical or radiographic suspicion of ILD for which the diagnosis of ILD cannot be ruled out. Radiographic findings may include presence of lung parenchymal fibrosis, combined fibrosis and emphysema (CPFE), and/or interstitial lung abnormalities such as reticular opacities, traction bronchiectasis, honeycombing, or extensive ground glass opacities. Screening computed tomography (CT) scans must be submitted for independent central radiology review and results before randomization.
• Has clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses, including, but not limited to, any underlying pulmonary disorder and potential pulmonary involvement caused by any autoimmune, connective tissue, or inflammatory disorders, prior pneumonectomy, or requirement for supplemental oxygen.

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

США · 30 центров

• Highlands Oncology Group — Springdale
• Clinical Research Providence Medical Foundation — Fullerton
• UCLA Hematology-Oncology — Los Angeles
• UCSF Mission Bay Mission Hall — San Francisco
• University of Miami Hospital and Clinics Sylvester Comprehensive Cancer Center — Miami
• AdventHealth Orlando, Cancer Institute — Orlando
• H. Lee Moffitt Cancer Center and Research Institute, Inc — Tampa
• Rush MD Anderson Cancer Center — Chicago
• … и ещё 22 центра

Китай · 26 центров

• China-Japan Friendship Hospital — Пекин
• Beijing Cancer Hospital — Пекин
• Beijing Chest Hospital,Capital Medical University — Пекин
• Jilin Province Tumor Hospital — Changchun
• Hunan Cancer Hospital — Чанша
• Sichuan Cancer Hospital — Чэнду
• West China Hospital, Sichuan University — Чэнду
• Chongqing University Cancer Hospital — Чунцин
• … и ещё 18 центров

Франция · 18 центров

Список центров уточняется — проверьте первичный протокол.

Испания · 17 центров

Список центров уточняется — проверьте первичный протокол.

Италия · 16 центров

Список центров уточняется — проверьте первичный протокол.

Германия · 14 центров

Список центров уточняется — проверьте первичный протокол.

Япония · 13 центров

Список центров уточняется — проверьте первичный протокол.

Бразилия · 11 центров

• Departmento de Pesquisa Clinica- Hospital de Amor de Barretos — Barretos
• Cepon - Centro de Pesquisas Oncolăgicas de Santa Catarina — Florianópolis
• Clínica de Neoplasias Litoral — Itajaí
• Hospital São Lucas Da Pucrs — Porto Alegre
• Cepho Centro de Estudos E Pesquisas de Hematologia E Oncologia — Santo André
• Fundacao Faculdade Regional de Medicina de Sao Jose Do Rio Preto — São José do Rio Preto
• ICESP Instituto do Câncer do Estado de São Paulo Octavio Frias de Oliveira — São Paulo
• Hospital Sirio-Libanes — São Paulo
• … и ещё 3 центра

South Korea · 9 центров

Список центров уточняется — проверьте первичный протокол.

Греция · 8 центров

Список центров уточняется — проверьте первичный протокол.

Тайвань · 8 центров

Список центров уточняется — проверьте первичный протокол.

Австралия · 7 центров

• Ballarat Base Hospital — Ballarat
• Flinders Medical Centre (Fmc) — Bedford Park
• Chris O Brien Lifehouse — Camperdown
• Sunshine Hospital — St Albans
• St John of God Subiaco Hospital — Subiaco
• Townsville Cancer Centre — Townsville
• Princess Alexandra Hospital — Woolloongabba

Turkey (Türkiye) · 7 центров

Список центров уточняется — проверьте первичный протокол.

Бельгия · 6 центров

• Cliniques Universitaires Saint-Luc — Brussels
• Universitair Ziekenhuis Antwerpen — Edegem
• Jessa Ziekenhuis Hospital — Hasselt
• Centre Hospitalier Universitaire de Liege — Liège
• AZ DELTA — Roeselare
• Chu Ucl Namur — Yvoir

Австрия · 5 центров

• Landeskrankenhaus Feldkirch — Feldkirch
• Landesklinikum Krems — Krems
• Kepler University Hospital — Linz
• Wiener Gesundheitsverband Klinik Penzing — Vienna
• Klinik Floridsdorf — Vienna

Канада · 5 центров

• William Osler Health System - Brampton Civic Hospital — Brampton
• Cross Cancer Institute — Edmonton
• Institut Universitaire de Cardiologie et de Pneumologie de Quebec — Québec
• Princess Margaret Cancer Center — Toronto
• Cancercare Manitoba — Winnipeg

Венгрия · 5 центров

Список центров уточняется — проверьте первичный протокол.

Польша · 5 центров

Список центров уточняется — проверьте первичный протокол.

Португалия · 5 центров

Список центров уточняется — проверьте первичный протокол.

Нидерланды · 4 центра

Список центров уточняется — проверьте первичный протокол.

Румыния · 4 центра

Список центров уточняется — проверьте первичный протокол.

Чехия · 3 центра

Список центров уточняется — проверьте первичный протокол.

Швейцария · 3 центра

Список центров уточняется — проверьте первичный протокол.

Публикации

• Owonikoko TK, Byers L, Cheng Y, Hayashi H, Paz-Ares L, Perol M, Hu H, Qian M, Garcia CR, Godard J, Tang M, Rudin CM. IDeate-Lung02: a Phase 3 study of second-line ifinatamab deruxtecan in patients with relapsed small cell lung cancer. Future Oncol. 2025 Oct;21(25):3275-3282. doi: 10.1080/14796694.2025.2565995. Epub 2025 Oct 7. PMID 41055143

Идентификаторы

NCT: NCT06203210 · DS7300-188 · 2023-509628-16-00 · 2031230631

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗