A Clinical Trial of Calderasib (MK-1084) and Durvalumab in People With Non-Small Cell Lung Cancer (MK-1084-015/KANDLELIT-015)

Official title

A Phase 3, Randomized, Double-blind, Placebo- and Active-Comparator-Controlled Study of MK-1084 Plus Durvalumab Versus Placebo Plus Durvalumab in Participants With Locally Advanced, Unresected KRAS G12C-Mutant Non-Small Cell Lung Cancer Without Disease Progression Following Definitive Platinum-Based Chemoradiotherapy (KANDLELIT-015)

Overview

Researchers are looking for new ways to treat locally advanced non-small cell lung cancer (NSCLC) that is unresected and has a gene mutation called KRAS G12C. Researchers want to learn if calderasib (MK-1084) can be given with durvalumab, an immunotherapy, to treat NSCLC after chemotherapy and radiation therapy. The goal of this trial is to learn if participants who receive calderasib and durvalumab live longer without the cancer growing or spreading compared to participants who receive placebo and durvalumab.

Interventions

• Drug Calderasib
  Tablet for oral administration.
• Biological Durvalumab
  Solution for intravenous (IV) infusion.
• Other Placebo to MK-1084
  Placebo to MK-1084.

Primary outcome measures

• Progression-Free Survival (PFS) [Time frame: Up to approximately 6 years]

Secondary outcome measures (9)

• Overall Survival (OS) [Time frame: Up to approximately 9 years]
• Number of Participants Who Experience an Adverse Events (AEs) [Time frame: Up to approximately 9 years]
• Number of Participants Who Discontinue Study Treatment Due to an AE [Time frame: Up to approximately 9 years]
• Objective Response Rate (ORR) [Time frame: Up to approximately 9 years]
• Duration of Response (DOR) [Time frame: Up to approximately 9 years]
• Distant Metastasis-Free Survival (DMFS) [Time frame: Up to approximately 9 years]
• Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status (GHS)/Quality of Life (QoL) (Items 29 & 30) Combined Score [Time frame: Baseline and up to approximately 9 years]
• Change From Baseline in Physical Functioning (EORTC QLQ-C30 Items 1-5) Combined Score [Time frame: Baseline and up to approximately 9 years]
• Change from Baseline in Role Functioning (EORTC QLQ-C30 Items 6 & 7) Combined Score [Time frame: Baseline and up to approximately 9 years]

Eligibility criteria

Inclusion criteria

The main inclusion criteria include but are not limited to the following:

• Has a histological or cytological diagnosis of locally advanced, unresected Stage II (node-positive) to III non-small cell lung cancer (NSCLC) with predominantly nonsquamous histology.
• Has completed definitive platinum-based concurrent chemoradiotherapy (CCRT) prior to enrollment, without disease progression.
• Has provided a tumor tissue sample for central laboratory testing of Kirsten rat sarcoma G12C (KRAS G12C) status, programmed cell death ligand 1 (PD-L1) status, and biomarker research.
• Tumor tissue sample has a demonstrated presence of KRAS G12C mutation and an evaluable PD-L1 status result.
• If human immunodeficiency virus (HIV)-infected, has well-controlled HIV on antiretroviral therapy (ART).
• If hepatitis B surface antigen (HBsAg)-positive, has undetectable hepatitis B virus (HBV) viral load and has received HBV antiviral therapy.
• If has a history of hepatitis C virus (HCV) infection, has undetectable HCV viral load.
• Has a body weight ≥35 kg.

Exclusion criteria

The main exclusion criteria include but are not limited to the following:

• Has a diagnosis of small cell lung cancer or mixed tumors with small cell elements.
• Has a gastrointestinal disorder affecting absorption or is unable to swallow orally administered medication.
• Has active inflammatory bowel disease requiring immunosuppressive medication or previous clear history of inflammatory bowel disease.
• Has uncontrolled, significant cardiovascular disease or cerebrovascular disease.
• Is HIV-infected with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease.
• Has received prior treatment (other than definitive CCRT) for NSCLC.
• Has a 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.
• Has a history of, or has current, (noninfectious) pneumonitis/interstitial lung disease that required/requires steroids.
• Has an active infection requiring systemic therapy.
• Has a history of stem cell/solid organ transplant.
• 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

Ukraine · 13 centers

• Regional Municipal Non-profit Enterprise "Bukovinian Clinical Oncology Center" ( Site 2002 — Chernivtsi
• Medical Center "Mriya Med-Service"-Clinical Research Department ( Site 2012) — Kryvyi Rih
• Communal Non-Commercial Enterprise "Prykarpatski Clinical Oncological Center" of Ivano-Fra — Ivano-Frankivsk
• Private Enterprise Private Manufacturing Company Acinus-Medical and Diagnostic Centre ( Si — Kropyvnytskyi
• Ukrainian Center of Tomotherapy ( Site 2014) — Kropyvnytskyi
• Shalimov Institute of Surgery and Transplantation ( Site 2003) — Kyiv
• Lviv Oncology Regional Treatment and Diagnostic Center ( Site 2009) — Lviv
• Lviv Territorial Medical Union Multidisciplinary Clinical Hospital ( Site 2000) — Lviv
• … and 5 more centers

China · 10 centers

• Zhongshan Hospital Affiliated to Xiamen University ( Site 2213) — Xiamen
• The First Affiliated Hospital of Xiamen University. ( Site 2239) — Xiamen
• Guangxi Medical University Affiliated Tumor Hospital ( Site 2202) — Qingxiu District
• Union Hospital Tongji Medical College Huazhong University of Science and Technology-Medica — Wuhan
• Hubei Cancer Hospital ( Site 2203) — Wuhan
• Nanjing Drum Tower Hospital ( Site 2224) — Nanjing
• Shandong Cancer Hospital ( Site 2200) — Jinan
• Zhongshan Hospital affiliated to Fudan University ( Site 2215) — Shanghai
• … and 2 more centers

South Korea · 6 centers

• National Cancer Center ( Site 2505) — Goyang-si
• Ajou University Hospital ( Site 2504) — Suwon
• Chungbuk National University Hospital ( Site 2502) — Cheongju-si
• Keimyung University Dongsan Hospital ( Site 2503) — Daegu
• Severance Hospital, Yonsei University Health System ( Site 2501) — Seoul
• Asan Medical Center ( Site 2500) — Seoul

Spain · 6 centers

• Institut Català d'Oncologia (ICO) - Girona-Oncología Médica ( Site 1807) — Girona
• Fundación Instituto Valenciano de Oncología ( Site 1809) — Valencia
• HOSPITAL GENERAL UNIVERSITARIO GREGORIO MARAÑON ( Site 1803) — Madrid
• Hospital Clinico San Carlos ( Site 1810) — Madrid
• Hospital Universitario La Paz ( Site 1808) — Madrid
• Hospital Universitario Virgen Macarena ( Site 1805) — Seville

Argentina · 4 centers

• Clinica Adventista Belgrano ( Site 0304) — Ciudad Autonoma de Buenos Aires
• Instituto de Investigaciones Clínicas Mar del Plata ( Site 0303) — Mar del Plata
• Hospital Britanico de Buenos Aires ( Site 0305) — Buenos Aires
• Sanatorio Parque ( Site 0302) — Rosario

Taiwan · 4 centers

• Taipei Medical University Shuang Ho Hospital ( Site 2612) — New Taipei City
• National Cheng Kung University Hospital ( Site 2601) — Tainan
• Mackay Memorial Hospital ( Site 2611) — Taipei
• Tri-Service General Hospital ( Site 2608) — Taipei

Greece · 3 centers

• Athens Medical Center ( Site 1201) — Athens
• Metaxa Cancer Hospital of Piraeus ( Site 1203) — Piraeus
• University General Hospital of Alexandroupoli ( Site 1206) — Alexandroupoli

Netherlands · 3 centers

• Radboudumc ( Site 1504) — Nijmegen
• Leids Universitair Medisch Centrum ( Site 1503) — Leiden
• University Medical Center Groningen ( Site 1505) — Groningen

United States · 2 centers

• NHO Revive Research Institute LLC ( Site 0118) — Lincoln
• New York Oncology Hematology P.C ( Site 9000) — Albany

Germany · 1 center

• Gemeinschaftspraxis für Hämatologie und Onkologie Münster ( Site 1108) — Münster

Italy · 1 center

• Fondazione Policlinico Universitario Agostino Gemelli IRCCS - Università Cattolica del Sac — Rome

Identifiers

NCT: NCT07554339 · 1084-015 · 2025-522038-29-00 · U1111-1321-6971 · MK-1084-015 · KANDLELIT-015 · jRCT2021260021

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗