Multiple Omics Sequencing Technologies in Predicting the Efficacy and Monitoring the Recurrence of Non-Small Cell Lung Cancer

Official title

Applications of Multiple Omics Sequencing Technologies in Predicting the Efficacy and Monitoring the Recurrence of Non-Small Cell Lung Cancer: A Prospective, Non-Interventional Study

Overview

Lung cancer is one of the diseases with the highest global incidence and mortality. Studies have confirmed that liquid biopsy markers such as minimal residual disease (MRD) detection in solid tumors, circulating tumor DNA (ctDNA), and T-cell receptor (TCR) have roles in monitoring disease status, prognostic evaluation, recurrence prediction, and guiding treatment decisions in NSCLC patients. Peripheral blood dynamic monitoring indicators have broad application prospects and may completely transform the treatment paradigm for NSCLC patients in the future. However, current limitations exist, including the need to improve the sensitivity of detection methods, the lack of uniform criteria for defining MRD positivity, the undetermined timing and cycle of MRD testing, and insufficient results from large-scale prospective clinical trials. Therefore, the transition of peripheral blood-based dynamic testing to routine clinical practice still requires results from large-scale prospective clinical trials. This study intends to conduct a prospective clinical trial enrolling NSCLC patients with different stages and treatment modalities (immunotherapy combined with chemotherapy, targeted therapy combined with chemotherapy, neoadjuvant therapy, adjuvant therapy). Based on peripheral blood and tumor tissue samples, it will systematically integrate multi-omics approaches including ctDNA testing, whole exome sequencing (WES), genome-wide methylation sequencing (GM-seq), and TCR-seq to carry out comprehensive, precise, and dynamic biomarker detection for efficacy monitoring and recurrence prediction, providing new methods and evidence for the clinical application of dynamic liquid biopsy monitoring in lung cancer.

Primary outcome measures

• Liquid Biopsy Biomarkers [Time frame: From enrollment to the end of monitoring at 3 years or the occurrence of disease progression.]

Secondary outcome measures (2)

• Comparison of MRD and Conventional Imaging [Time frame: From enrollment to the end of monitoring at 3 years or the occurrence of disease progression.]
• The appropriate timing for minimal residual disease (MRD) testing [Time frame: From enrollment to the end of monitoring at 3 years or the occurrence of disease progression.]

Eligibility criteria

Inclusion criteria

• Voluntarily signed the informed consent;
• Aged 18 years or older;
• Expected life expectancy of ≥3 months;
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1 (see Appendix 1);
• Histologically or cytologically confirmed non-small cell lung cancer (NSCLC) patients;
• Classified as stage II, III, or IV according to the AJCC TNM staging system (9th edition);
• Willing to provide blood samples and pre-treatment paraffin-embedded tissue samples;
• With evaluable target lesions for efficacy assessment.

Exclusion criteria

• In the investigator's opinion, unsuitable for peripheral blood collection due to complications or other circumstances;
• Active, known, or suspected autoimmune diseases (except vitiligo, type 1 diabetes, residual hypothyroidism caused by autoimmune thyroiditis requiring only hormone replacement therapy, or conditions not expected to relapse without external stimulation);
• Active tuberculosis (TB) infection confirmed by chest X-ray, sputum examination, and clinical physical examination. Patients with a history of active TB infection within the past 1 year, even if treated, will be excluded. Patients with a history of active TB infection more than 1 year ago will also be excluded unless they can demonstrate that previous antitubercular treatment was fully effective;
• Comorbidities requiring treatment with immunosuppressive drugs, or comorbidities requiring systemic or local corticosteroids at immunosuppressive doses;
• Pregnant or lactating;
• Positive for human immunodeficiency virus antibody (HIVAb), active hepatitis B virus infection (HBsAg-positive and HBV-DNA > 10³ copies/ml), or hepatitis C virus infection (HCV antibody-positive and HCV-RNA > the lower limit of detection at the study center);
• History of severe neurological or psychiatric disorders, including but not limited to: dementia, depression, seizures, bipolar disorder, etc.;
• Use of any antitumor-active drugs prior to blood sample collection;
• Previous history of other malignancies (excluding non-melanoma skin cancer and the following in situ carcinomas: bladder, stomach, colon, endometrium, cervix/dysplasia, melanoma, or breast cancer);
• Administration of live vaccines within 28 days prior to blood sample collection.

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

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

China · 1 center

• National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chine — Beijing

Publications

• Pellini B, Chaudhuri AA. Circulating Tumor DNA Minimal Residual Disease Detection of Non-Small-Cell Lung Cancer Treated With Curative Intent. J Clin Oncol. 2022 Feb 20;40(6):567-575. doi: 10.1200/JCO.21.01929. Epub 2022 Jan 5. PMID 34985936
• Fujimoto D, Yoshioka H, Kataoka Y, Morimoto T, Hata T, Kim YH, Tomii K, Ishida T, Hirabayashi M, Hara S, Ishitoko M, Fukuda Y, Hwang MH, Sakai N, Fukui M, Nakaji H, Morita M, Mio T, Yasuda T, Sugita T, Hirai T. Pseudoprogression in Previously Treated Patients with Non-Small Cell Lung Cancer Who Received Nivolumab Monotherapy. J Thorac Oncol. 2019 Mar;14(3):468-474. doi: 10.1016/j.jtho.2018.10.167. PMID 30468872
• Dong S, Wang Z, Zhang JT, Yan B, Zhang C, Gao X, Sun H, Li YS, Yan HH, Tu HY, Liu SM, Gong Y, Gao W, Huang J, Liao RQ, Lin JT, Ke EE, Xu Z, Zhang X, Xia X, Li AN, Liu SY, Pan Y, Yang JJ, Zhong WZ, Yi X, Zhou Q, Yang XN, Wu YL. Circulating Tumor DNA-Guided De-Escalation Targeted Therapy for Advanced Non-Small Cell Lung Cancer: A Nonrandomized Controlled Trial. JAMA Oncol. 2024 Jul 1;10(7):932-940. PMID 38869865
• Mack PC, Miao J, Redman MW, Moon J, Goldberg SB, Herbst RS, Melnick MA, Walther Z, Hirsch FR, Politi K, Kelly K, Gandara DR. Circulating Tumor DNA Kinetics Predict Progression-Free and Overall Survival in EGFR TKI-Treated Patients with EGFR-Mutant NSCLC (SWOG S1403). Clin Cancer Res. 2022 Sep 1;28(17):3752-3760. doi: 10.1158/1078-0432.CCR-22-0741. PMID 35713632
• Hellmann MD, Nabet BY, Rizvi H, Chaudhuri AA, Wells DK, Dunphy MPS, Chabon JJ, Liu CL, Hui AB, Arbour KC, Luo J, Preeshagul IR, Moding EJ, Almanza D, Bonilla RF, Sauter JL, Choi H, Tenet M, Abu-Akeel M, Plodkowski AJ, Perez Johnston R, Yoo CH, Ko RB, Stehr H, Gojenola L, Wakelee HA, Padda SK, Neal JW, Chaft JE, Kris MG, Rudin CM, Merghoub T, Li BT, Alizadeh AA, Diehn M. Circulating Tumor DNA Analy PMID 32046999
• Provencio M, Serna-Blasco R, Nadal E, Insa A, Garcia-Campelo MR, Casal Rubio J, Domine M, Majem M, Rodriguez-Abreu D, Martinez-Marti A, De Castro Carpeno J, Cobo M, Lopez Vivanco G, Del Barco E, Bernabe Caro R, Vinolas N, Barneto Aranda I, Viteri S, Pereira E, Royuela A, Calvo V, Martin-Lopez J, Garcia-Garcia F, Casarrubios M, Franco F, Sanchez-Herrero E, Massuti B, Cruz-Bermudez A, Romero A. Over PMID 35576508
• Forde PM, Spicer J, Lu S, Provencio M, Mitsudomi T, Awad MM, Felip E, Broderick SR, Brahmer JR, Swanson SJ, Kerr K, Wang C, Ciuleanu TE, Saylors GB, Tanaka F, Ito H, Chen KN, Liberman M, Vokes EE, Taube JM, Dorange C, Cai J, Fiore J, Jarkowski A, Balli D, Sausen M, Pandya D, Calvet CY, Girard N; CheckMate 816 Investigators. Neoadjuvant Nivolumab plus Chemotherapy in Resectable Lung Cancer. N Engl PMID 35403841
• Gale D, Heider K, Ruiz-Valdepenas A, Hackinger S, Perry M, Marsico G, Rundell V, Wulff J, Sharma G, Knock H, Castedo J, Cooper W, Zhao H, Smith CG, Garg S, Anand S, Howarth K, Gilligan D, Harden SV, Rassl DM, Rintoul RC, Rosenfeld N. Residual ctDNA after treatment predicts early relapse in patients with early-stage non-small cell lung cancer. Ann Oncol. 2022 May;33(5):500-510. doi: 10.1016/j.annon PMID 35306155

Identifiers

NCT: NCT07057102 · NCC5160

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗