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

Official title

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)

Overview

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.

Interventions

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

Primary outcome measures

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

Secondary outcome measures (11)

• Overall Survival (OS) [Time frame: Up to ~11 years]
• Distant Metastasis-Free Survival (DMFS) [Time frame: Up to ~11 years]
• Lung Cancer Specific Survival (LCSS) [Time frame: 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 [Time frame: Up to ~11 years]
• Change from Baseline in the EORTC-QLQ-C30 Physical Functioning (Items 1-5) Combined Score [Time frame: Up to ~11 years]
• Change from Baseline in the EORTC-QLQ-C30 Role Functioning (Items 6 and 7) Combined Score [Time frame: Up to ~11 years]
• Change from Baseline in the EORTC-QLQ-C30 Dyspnea (Item 8) Score [Time frame: 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 [Time frame: Up to ~11 years]
• Change from Baseline in the EORTC-QLQ-LC24 Chest Pain (Item 40) Score [Time frame: Up to ~11 years]
• Number of Participants Who Experience an Adverse Event (AE) [Time frame: Up to ~13.5 years]
• Number of Participants Who Discontinue Study Treatment Due to an AE [Time frame: Up to ~13.5 years]

Eligibility criteria

Inclusion criteria

• 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

Exclusion criteria

• 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Treatment

Study locations

China · 20 centers

• Peking University People's Hospital ( Site 2100) — Beijing
• Beijing Cancer hospital ( Site 2106) — Beijing
• Peking Union Medical College Hospital ( Site 2105) — Beijing
• Chongqing University Three Gorges Hospital ( Site 2138) — Chongqing
• The First Affiliated Hospital Of Fujian Medical University ( Site 2123) — Fuzhou
• Sun Yat-sen University Cancer Center ( Site 2134) — Guangzhou
• Guangxi Medical University Cancer Hospital ( Site 2115) — Nanning
• Fourth Hospital Of Hebei Medical University ( Site 2107) — Hshijiazhuang
• … and 12 more centers

Ukraine · 14 centers

• 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
• … and 6 more centers

Turkey (Türkiye) · 11 centers

• 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
• … and 3 more centers

Spain · 9 centers

• 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
• … and 1 more center

Greece · 6 centers

• 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 centers

• 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

Argentina · 4 centers

• 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

Taiwan · 4 centers

• 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

Australia · 2 centers

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

Canada · 2 centers

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

Hong Kong · 2 centers

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

Brazil · 1 center

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

France · 1 center

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

Italy · 1 center

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

Identifiers

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

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗