MK-3475A±Calderasib (MK-1084) in Completely Resected Stage IIA-IIIB (N2) KRAS G12Cm NSCLC (MK-1084-013)

Официальное название

A Phase 3, Randomized, Double-blind Study of Adjuvant MK-1084 Plus Subcutaneous Pembrolizumab and Berahyaluronidase Alfa (MK-3475A) Versus Adjuvant Placebo Plus MK-3475A in Participants With Completely Resected Stage IIA-IIIB (N2), KRAS G12C-mutant Non-small Cell Lung Cancer Following Receipt of Either Neoadjuvant Pembrolizumab Plus Chemotherapy or Adjuvant Chemotherapy (KANDLELIT-013)

Обзор

This is a phase 3, randomized, double-blind study of adjuvant calderasib plus subcutaneous pembrolizumab and berahyaluronidase alfa (MK-3475A) versus adjuvant placebo plus MK-3475a in participants with completely resected stage IIA-IIIB (N2), KRAS G12C-mutant non-small cell lung cancer following receipt of either neoadjuvant pembrolizumab plus chemotherapy or adjuvant chemotherapy. The primary goal of the study is to compare adjuvant calderasib plus MK-3475A to adjuvant placebo plus MK-3475A with respect to disease-free survival (DFS) as assessed by the investigator.

Вмешательства

• Препарат Calderasib
  MK-1084 oral tablet
• Биопрепарат MK-3475A
  Fixed dose coformulated product of hyaluronidase/pembrolizumab administered via SC injection.
• Препарат Placebo
  Placebo oral tablet

Первичные конечные точки

• Disease-free Survival (DFS) [Срок оценки: Up to ~11 years]

Вторичные конечные точки (11)

• Overall Survival (OS) [Срок оценки: Up to ~11 years]
• Distant Metastasis-Free Survival (DMFS) [Срок оценки: Up to ~11 years]
• Lung Cancer Specific Survival (LCSS) [Срок оценки: Up to ~11 years]
• Change from Baseline in the European Organization for Research and Treatment of Cancer (EORTC)-Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status (Item 29) and Quality of Life (Item 30) Combined Score [Срок оценки: Up to ~11 years]
• Change from Baseline in the EORTC-QLQ-C30 Physical Functioning (Items 1-5) Combined Score [Срок оценки: Up to ~11 years]
• Change from Baseline in the EORTC-QLQ-C30 Role Functioning (Items 6 and 7) Combined Score [Срок оценки: Up to ~11 years]
• Change from Baseline in the EORTC-QLQ-C30 Dyspnea (Item 8) Score [Срок оценки: Up to ~11 years]
• Change from Baseline in the EORTC-Quality of Life Questionnaire-Lung Cancer 24 (QLQ-LC24) Coughing (Items 31 and 52) Combined Score [Срок оценки: Up to ~11 years]
• Change from Baseline in the EORTC-QLQ-LC24 Chest Pain (Item 40) Score [Срок оценки: Up to ~11 years]
• Number of Participants Who Experience an Adverse Event (AE) [Срок оценки: Up to ~13.5 years]
• Number of Participants Who Discontinue Study Treatment Due to an AE [Срок оценки: Up to ~13.5 years]

Критерии участия

Критерии включения

• Has a histological/cytological diagnosis of non-small cell lung cancer (NSCLC) with predominantly nonsquamous histology and meets one of the following criteria:

• Has newly diagnosed, treatment-naïve, resectable, clinical Stage IIA-IIIB (N2) NSCLC
• Has completely resected, pathological Stage IIA-IIIB (N2) NSCLC, including those previously treated outside the study with neoadjuvant platinum-doublet chemotherapy plus pembrolizumab or MK-3475A, or those who received adjuvant platinum-doublet chemotherapy.
• Tumor tissue shows the presence of Kirsten rat sarcoma viral oncogene homolog G12C (KRAS G12C) mutation
• No more than 12 weeks have elapsed between either the surgery following neoadjuvant treatment or last dose of adjuvant platinum-based chemotherapy and the first dose of investigational adjuvant study intervention.
• Has no evidence of disease based on postsurgical radiological assessment as documented by contrast-enhanced chest/abdomen computed tomography (or magnetic resonance imaging) within 28 days before randomization
• Has an Eastern Cooperative Oncology Group performance status of 0 or 1 within 10 days before the first dose of the study intervention
• Human immunodeficiency virus-infected participants must have well controlled HIV on antiretroviral therapy
• Participants who are Hepatitis B surface antigen positive are eligible if they have received hepatitis B virus (HBV) antiviral therapy and have undetectable HBV viral load
• Participants with history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable

Критерии исключения

• Has a diagnosis of any 1 of the following tumor types/locations: small cell lung cancer or, for mixed tumors, presence of small cell elements, neuroendocrine tumor with large cell components, sarcomatoid carcinoma, or NSCLC involving the superior sulcus
• HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
• Has active inflammatory bowel disease requiring immunosuppressive medication or previous clear history of inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis, chronic diarrhea)
• Has uncontrolled, significant cardiovascular disease or cerebrovascular disease within the 6 months preceding study intervention
• Is unable to swallow orally administered medication, or has a gastrointestinal disorder affecting absorption (e.g. gastrectomy, partial bowel obstruction, or malabsorption)
• Has known additional malignancy that is progressing or has required active treatment within the past 3 years
• Has an active autoimmune disease that has required systemic treatment in the past 2 years except replacement therapy
• Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
• Has active infection requiring systemic therapy
• Has not adequately recovered from major surgery or has ongoing surgical complications

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

Тройное слепое

Основная цель

Лечение

Центры проведения

Китай · 20 центров

• Peking University People's Hospital ( Site 2100) — Пекин
• Beijing Cancer hospital ( Site 2106) — Пекин
• Peking Union Medical College Hospital ( Site 2105) — Пекин
• Chongqing University Three Gorges Hospital ( Site 2138) — Чунцин
• The First Affiliated Hospital Of Fujian Medical University ( Site 2123) — Фучжоу
• Sun Yat-sen University Cancer Center ( Site 2134) — Гуанчжоу
• Guangxi Medical University Cancer Hospital ( Site 2115) — Nanning
• Fourth Hospital Of Hebei Medical University ( Site 2107) — Hshijiazhuang
• … и ещё 12 центров

Украина · 14 центров

• COMMUNAL NONPROFIT ENTERPRISE CLINICAL CENTER OF ONCOLOGY, HEMATOLOGY, TRANSPLANTOLOGY AND — Cherkasy
• Regional Municipal Non-profit Enterprise "Bukovinian Clinical Oncology Center" ( Site 1909 — Chernivtsi
• Medical Center "Mriya Med-Service" ( Site 1911) — Kryvyi Rih
• Communal Non-Commercial Enterprise Prykarpatski Clinical Oncological Center of Ivano-Frank — Ivano-Frankivsk
• Private Enterprise Private Manufacturing Company Acinus-Medical and Diagnostic Centre ( Si — Kropyvnytskyi
• Ukrainian Center of Tomotherapy ( Site 1917) — Kropyvnytskyi
• Communal noncommercial enterprise of Lviv regional council "Lviv oncological regional ther — Lviv
• Lviv Territorial Medical Union Multidisciplinary Clinical Hospital ( Site 1902) — Lviv
• … и ещё 6 центров

Turkey (Türkiye) · 11 центров

• Baskent University Dr. Turgut Noyan Research and Training Center ( Site 1812) — Adana
• Adana Medical Park Seyhan Hastanesi ( Site 1827) — Adana
• Ankara Atatürk Sanatoryum Eğitim ve Araştırma Hastanesi ( Site 1825) — Ankara
• Hacettepe Universite Hastaneleri ( Site 1810) — Ankara
• Ankara Bilkent Şehir Hastanesi ( Site 1811) — Ankara
• Liv Hospital Ankara ( Site 1828) — Ankara
• Kartal Lütfi Kırdar Şehir Hastanesi ( Site 1826) — Istanbul
• İnönü Üniversitesi Turgut Özal Tıp Merkezi ( Site 1815) — Malatya
• … и ещё 3 центра

Испания · 9 центров

• Hospital Insular de Gran Canaria ( Site 1704) — Las Palmas de Gran Canaria
• Institut Català d'Oncologia (ICO) - Girona ( Site 1703) — Girona
• Hospital Puerta de Hierro ( Site 1705) — Majadahonda
• Hospital Universitari Vall d'Hebron ( Site 1700) — Barcelona
• Hospital Clinico San Carlos ( Site 1706) — Madrid
• Hospital Universitario la Paz ( Site 1710) — Madrid
• HOSPITAL UNIVERSITARIO QUIRONSALUD MADRID ( Site 1707) — Madrid
• H.R.U Malaga - Hospital General ( Site 1708) — Málaga
• … и ещё 1 центр

Греция · 6 центров

• Evangelismos General Hospital of Athens ( Site 1204) — Athens
• Errikos Dunant Hospital Center ( Site 1201) — Athens
• THORACIC GENERAL HOSPITAL OF ATHENS "I SOTIRIA" ( Site 1206) — Athens
• Athens Medical Center ( Site 1202) — Athens
• Metaxa Cancer Hospital of Piraeus ( Site 1207) — Piraeus
• G. Papanikolaou General Hospital ( Site 1203) — Thessaloniki

South Korea · 5 центров

• National Cancer Center ( Site 3603) — Goyang-si
• The Catholic University of Korea St. Vincent s Hospital ( Site 3602) — Suwon
• Keimyung University Dongsan Hospital ( Site 3605) — Daegu
• Severance Hospital Yonsei University Health System ( Site 3601) — Seoul
• Asan Medical Center ( Site 3600) — Seoul

Аргентина · 4 центра

• Instituto Alexander Fleming ( Site 0310) — Ciudad Autónoma de Buenos Aires
• Sanatorio Parque ( Site 0311) — Rosario
• Hospital Italiano de Buenos Aires-Clinical Oncology ( Site 0306) — CABA
• Centro de Educación Médica e Investigaciones clínicas "Dr. Norberto Quirno" (CEMIC) ( Site — CABA

Тайвань · 4 центра

• Taipei Medical University Shuang Ho Hospital ( Site 3700) — New Taipei City
• National Cheng Kung University Hospital ( Site 3706) — Tainan
• Mackay Memorial Hospital ( Site 3701) — Taipei
• Tri-Service General Hospital ( Site 3708) — Taipei

Австралия · 2 центра

• Northern Beaches Hospital ( Site 3009) — Frenchs Forest
• Peninsula University Hospital ( Site 3011) — Frankston

Канада · 2 центра

• Moncton Hospital ( Site 0200) — Moncton
• Centre Hospitalier de l'Université de Montréal ( Site 0219) — Montreal

Гонконг · 2 центра

• Queen Mary Hospital ( Site 3100) — Гонконг
• Tuen Mun Hospital ( Site 3102) — Гонконг

Бразилия · 1 центр

• Faculdade de Medicina do ABC ( Site 0415) — Santo André

Франция · 1 центр

• Centre de Cancérologie du Grand Montpellier ( Site 1016) — Montpellier

Италия · 1 центр

• Fondazione IRCCS Istituto Nazionale dei Tumori ( Site 1400) — Milan

Идентификаторы

NCT: NCT07431827 · 1084-013 · U1111-1312-0627 · 2024-517337-41-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗