Sacituzumab Tirumotecan (MK-2870) in Combination With Pembrolizumab Versus Pembrolizumab Alone in Metastatic Non-small Cell Lung Cancer (NSCLC) With Programmed Cell Death Ligand 1 (PD-L1) Tumor Proportion Score (TPS) ≥ 50% (MK-2870-007)

Официальное название

A Randomized, Open-label, Phase 3 Study of MK-2870 in Combination With Pembrolizumab Compared to Pembrolizumab Monotherapy in the First-line Treatment of Participants With Metastatic Non-small Cell Lung Cancer With PD-L1 TPS Greater Than or Equal to 50% (TroFuse-007)

Обзор

The primary objective of the study is to compare sacituzumab tirumotecan combined with pembrolizumab to pembrolizumab alone with respect to overall survival (OS). The primary hypothesis is that the combination of sacituzumab tirumotecan and pembrolizumab is superior to pembrolizumab alone with respect to OS. All participants who have completed the first course of pembrolizumab may be eligible for up to an additional 9 cycles of pembrolizumab monotherapy if there is blinded independent central review (BICR)-verified progressive disease by Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST 1.1) after initial treatment.

Вмешательства

• Биопрепарат Sacituzumab tirumotecan
  IV infusion
• Биопрепарат Pembrolizumab
  IV infusion
• Препарат Supportive care measures
  Participants are allowed to take supportive care measures at the discretion of the investigator. Prophylactic supportive care measures may include but are not limited to antiemetic agents, antidiarrheal agents, granulocyte and erythroid growth factors, and blood transfusions

Первичные конечные точки

• Overall Survival (OS) [Срок оценки: Up to approximately 49 months]

Вторичные конечные точки (12)

• Progression free survival (PFS) [Срок оценки: Up to approximately 49 months]
• Objective Response (OR) [Срок оценки: Up to approximately 49 months]
• Duration of Response (DOR) [Срок оценки: Up to approximately 49 months]
• Change from Baseline in Global Health Status/Quality of Life (QOL) [European Organisation for Research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire (QLQ-C30) 29 Items and 30] Score [Срок оценки: Baseline and up to approximately 77 months]
• Change From Baseline in Dyspnea (EORTC QLQ-C30 Item 8) Score [Срок оценки: Baseline and up to approximately 77 months]
• Change From Baseline in Cough (EORTC QLQ-LC13 Item 31) Score [Срок оценки: Baseline and up to approximately 77 months]
• Change From Baseline in Chest Pain (EORTC QLQ-LC13 item 40) Score [Срок оценки: Baseline and up to approximately 77 months]
• Time to Deterioration (TTD) Based on Change From Baseline in Global Health Status (GHS)/ QOL Score (EORTC QLQ-C30 Item 29 and 30) [Срок оценки: Up to approximately 77 months]
• Time to Deterioration (TTD) Based on Change From Baseline in Dyspnea Score (EORTC QLQ-C30 Item 8) [Срок оценки: Up to approximately 77 months]
• Time to Deterioration (TTD) Based on Change From Baseline in Cough Score (EORTC QLQ-LC13 Item 31). [Срок оценки: Up to approximately 77 months]
• Time to Deterioration (TTD) Based on Change From Baseline in Chest Pain Score (EORTC QLQ-LC13 Item 40) [Срок оценки: Up to approximately 77 months]
• Percentage of Participants That Experience at Least 1 Adverse Event [Срок оценки: Up to approximately 77 months]

Критерии участия

Критерии включения

• Histologically or cytologically confirmed diagnosis of squamous or nonsquamous NSCLC

• Confirmation that epidermal growth factor receptor- (EGFR-), anaplastic lymphoma kinase- (ALK-), or proto-oncogene tyrosine-protein kinase ROS (ROS1-) directed therapy is not indicated as primary therapy
• Provided tumor tissue that demonstrates programmed cell death ligand 1 (PD-L1) expression in ≥50% of tumor cells as assessed by an immunohistochemistry (IHC) central laboratory
• An Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 assessed within 7 days before randomization.
• A life expectancy of at least 3 months.
• Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on antiretroviral therapy (ART)

Критерии исключения

• Diagnosis of small cell lung cancer or, for mixed tumors, presence of small cell elements.
• Has Grade ≥2 peripheral neuropathy.
• History of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, or severe corneal disease that prevents/delays corneal healing.
• Has active inflammatory bowel disease requiring immunosuppressive medication or previous clear history of inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis, or chronic diarrhea).
• Has uncontrolled, significant cardiovascular disease or cerebrovascular disease within the 6 months preceding study intervention.
• Received prior systemic anticancer therapy for their metastatic NSCLC.
• Received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent, or with an agent directed to another stimulatory or coinhibitory T-cell receptor Note: Prior treatment with an anti-PD-1, anti-PD- L1, or anti-PD-L2 agent in the neoadjuvant or adjuvant setting for nonmetastatic resectable NSCLC is allowed as long as therapy was completed at least 12 months before diagnosis of metastatic NSCLC.
• Received prior systemic anticancer therapy including investigational agents within 4 weeks before randomization.
• Received radiation therapy to the lung that is >30 Gy within 6 months of start of study intervention.
• Received prior radiotherapy within 2 weeks of start of study intervention, or radiation-related toxicities, requiring corticosteroids.
• Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines are allowed.
• Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
• Known additional malignancy that is progressing or has required active treatment within the past 3 years.
• Known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
• Known intolerance to sacituzumab tirumotecan or pembrolizumab and/or any of their excipients; for pembrolizumab, severe hypersensitivity (≥Grade 3) is exclusionary.
• Known hypersensitivity to sacituzumab tirumotecan or other biologic therapy.
• Active autoimmune disease that has required systemic treatment in the past 2 years.
• History of (noninfectious) pneumonitis/interstitial lung disease (ILD) that required steroids or has current pneumonitis/ILD.
• Active infection requiring systemic therapy
• Concurrent active Hepatitis B and Hepatitis C virus infection.
• Human immunodeficiency virus (HIV)-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease.
• History of allogeneic tissue/solid organ transplant.
• Requires treatment with a strong inhibitor or inducer of Cytochrome P450 3A4 (CYP3A4) at least 14 days before the first dose of study intervention and throughout the study.

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

Простое слепое

Основная цель

Лечение

Центры проведения

Китай · 32 центра

• Second Affiliated hospital of Anhui Medical University ( Site 3133) — Хэфэй
• Beijing Cancer hospital-intrathoratic deparmtment II ( Site 3101) — Пекин
• Beijing Peking Union Medical College Hospital-pneumology department ( Site 3100) — Пекин
• Fujian Provincial Cancer Hospital ( Site 3131) — Фучжоу
• The First Affiliated hospital of Xiamen University-Breast Surgery ( Site 3107) — Xiamen
• The First Affiliated Hospital of Guangzhou Medical University ( Site 3134) — Гуанчжоу
• Southern Medical University Nanfang Hospital-Depatrment of Respiratory and Critical Care M — Гуанчжоу
• Affiliated Hospital of Guangdong Medical University ( Site 3123) — Zhanjiang
• … и ещё 24 центра

Япония · 30 центров

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США · 15 центров

• Mayo Clinic in Arizona - Phoenix ( Site 0147) — Phoenix
• Roy and Patricia Disney Family Cancer Center - Providence Saint Joseph Medical Center ( Si — Burbank
• Cancer Centers of Colorado St. Mary's Regional Hospital ( Site 0132) — Grand Junction
• Mayo Clinic in Florida-Mayo Clinic Comprehensive Cancer Center ( Site 0133) — Jacksonville
• Northwest Georgia Oncology Centers, a Service of Wellstar Cobb Hospital-Research ( Site 01 — Marietta
• The University of Louisville, James Graham Brown Cancer Center ( Site 0121) — Louisville
• New England Cancer Specialists ( Site 0143) — Westbrook
• University of Massachusetts Chan Medical School-Division of Hematology/Oncology ( Site 014 — Worcester
• … и ещё 7 центров

Германия · 11 центров

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Тайвань · 11 центров

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Turkey (Türkiye) · 11 центров

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Польша · 9 центров

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Испания · 9 центров

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Франция · 8 центров

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Италия · 8 центров

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South Korea · 8 центров

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Бразилия · 6 центров

• Irmandade da Santa Casa de Misericórdia de Porto Alegre ( Site 0409) — Porto Alegre
• Clinica Viver ( Site 0400) — Santa Maria
• Fundação Pio XII - Hospital de Câncer de Barretos ( Site 0402) — Barretos
• Fundação Faculdade Regional de Medicina de São José do Rio Preto ( Site 0406) — São José do Rio Preto
• Instituto Nacional de Câncer - INCA ( Site 0405) — Rio de Janeiro
• Núcleo de Pesquisa Clínica da Rede São Camilo ( Site 0401) — São Paulo

Мексика · 6 центров

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Перу · 6 центров

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Вьетнам · 6 центров

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Аргентина · 5 центров

• Instituto Alexander Fleming ( Site 0306) — Ciudad Autónoma de Buenos Aires
• Hospital Británico de Buenos Aires-Oncology ( Site 0304) — Buenos Aires
• Centro Privado de RMI Río Cuarto S.A. II ( Site 0310) — Río Cuarto
• Instituto de Oncología de Rosario ( Site 0301) — Rosario
• Hospital Aleman-Oncology ( Site 0300) — Buenos Aires

Австралия · 5 центров

• Port Macquarie - Mid North Coast Cancer Institute-Medical Oncology ( Site 3002) — Port Macquarie
• Westmead Hospital ( Site 3000) — Westmead
• Grampians Health-Medical Oncology ( Site 3001) — Ballarat Central
• Northern Hospital ( Site 3003) — Epping
• Peninsula University Hospital ( Site 3004) — Frankston

Чили · 5 центров

• Clinica Universidad Catolica del Maule-Oncology ( Site 0501) — Talca
• Orlandi Oncologia-Oncology ( Site 0504) — Santiago
• FALP-UIDO ( Site 0509) — Santiago
• Bradfordhill-Clinical Area ( Site 0507) — Santiago
• Bradford Hill Norte ( Site 0516) — Antofagasta

Португалия · 5 центров

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Великобритания · 5 центров

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Чехия · 4 центра

• Nemocnice AGEL Ostrava - Vitkovice a.s.-Plicni oddeleni ( Site 1103) — Ostrava
• Multiscan-Onkologicke a radiologicke centrum Multiscan Pardubice ( Site 1105) — Pardubice
• Vseobecna fakultni nemocnice v Praze-Onkologicka klinika ( Site 1106) — Prague
• Fakultni nemocnice Olomouc-Klinika plicnich nemoci a tuberkulozy ( Site 1102) — Olomouc

Канада · 3 центра

• William Osler Health System ( Site 0203) — Brampton
• Trillium Health Partners - Credit Valley Hospital ( Site 0202) — Mississauga
• McGill University Health Centre ( Site 0200) — Montreal

Колумбия · 3 центра

• FUNDACION CTIC CENTRO DE TRATAMIENTO E INVESTIGACION SOBRE CANCER LUIS CARLOS SARMIENTO AN — Bogotá
• IMAT S.A.S ( Site 0602) — Montería
• Oncologos del Occidente ( Site 0603) — Pereira

Дания · 3 центра

• Regionshospitalet Gødstrup-Kræftklinikken ( Site 1204) — Herning
• Aalborg Universitetshospital, Syd-Department of Oncology ( Site 1201) — Aalborg
• … и ещё 1 центр

Нидерланды · 3 центра

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Таиланд · 3 центра

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Идентификаторы

NCT: NCT06170788 · 2870-007 · MK-2870-007 · 2023-503376-24-00 · jRCT2051240089 · U1111-1287-1395

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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