Molecular Subtyping of Extensive Stage Small Cell Lung Cancer and Relevent Clinical Significance (MOSAIC)

To validate the predictive value of transcriptome-based molecular subtyping of extensive stage small cell lung cancer (SCLC) for the efficacy of programmed death-1(PD-1)/programmed death-ligand1(PD-L1) inhibitor in the first line setting; to explore the differences of immune microenvironment between different SCLC subtypes to reveal the mechanisms of immunotherapy resistance of SCLC

Study Overview

• Status: Completed
• Conditions: SCLC,Extensive Stage
• Intervention / Treatment: Drug: PD-(L)1 antibody immunotherapy

Detailed Description

This retrospective observational study examines the predictive value of transcriptome-based molecular subtyping of extensive stage SCLC for PD-1/PD-L1 inhibitor efficacy and explores immune microenvironment differences between subtypes to uncover immunotherapy resistance mechanisms. Patients with extensive stage SCLC receiving first-line standard treatment are enrolled, and baseline tumor tissue and peripheral blood samples are collected for transcriptome sequencing and immunohistochemistry (IHC). Based on results, patients are classified into four molecular subtypes, and treatment efficacy and safety are recorded. The study compares the efficacy between SCLC subtypes to determine if molecular typing predicts immunotherapy efficacy and investigates immune microenvironment differences between subtypes to uncover resistance mechanisms. Treatment regimens follow first-line extensive stage SCLC guidelines, including cisplatin+etoposide or carboplatin+etoposide and PD-(L)1 inhibitors, with options determined by the supervising physician.

• Study Type: Observational
• Enrollment (Actual): 168

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100042
      • Peking University Cancer Hospital & Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

This study includes adults (18-100 years) with untreated advanced SCLC. Eligible patients have an ECOG score of 0~2, an expected survival >3 months, and can provide tumor biopsy samples for transcripsome testing. They must have received first-line chemotherapy or chemotherapy combined with a PD-L1 inhibitor.

Participants are divided into two arms: Chemotherapy (80-100 cases) and Immunotherapy+chemotherapy (80-100 cases). Exclusion criteria include intolerance to chemotherapy, inability to provide tumor tissue samples, presence/history of other malignant tumors, and other reasons deeming them unfit for the study.

Description

Inclusion Criteria:

• The enrolled subjects shall meet all the following conditions at the same time.

  1. Male or female, aged 18 to 100 years
  2. Patients with untreated advanced small cell lung cancer clearly diagnosed by histopathology
  3. Be able to provide tumor biopsy tissue sample for molecular analysis
  4. Eastern Cooperative oncology Group (ECOG) score: 0~2
  5. Expected survival of more than 3 months.
  6. Has at least 1 measurable or evaluable tumor lesion with a longest diameter ≥ 10 mm at baseline (in case of lymph nodes, a shortest diameter ≥ 15 mm is required) according to RECIST v1.1
  7. Received first-line chemotherapy or chemotherapy＋PD-(L)1 inhibitor and be able to provide complete treatment information and efficacy evaluation results.
  8. Voluntary signed informed consent and expected good compliance.

Exclusion Criteria:

• Those meeting any of the following conditions may not be included.

  1. Patient unable to tolerate chemotherapy.
  2. Patients unable to provide tumor tissue samples for testing
  3. Patients with other malignant tumors or a history of other malignant tumors
  4. Patients have any other reason to be unfit to participate in this study.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
immunotherapy cohort; Extensive stage SCLC patients receiving first-line chemotherapy plus PD-(L)1 antibody treatment will be enrolled in this cohort. Baseline tumor tissue samples and peripheral blood samples will be collected for transcriptome and immunohistochemistry analysis etc.	Drug: PD-(L)1 antibody immunotherapy; The treatment regimen involved in this study follows guidelines for the first-line treatment of extensive stage SCLC: cisplatin+etoposide or carboplatin+etoposide and PD-(L)1 inhibitor.
chemotherapy cohort; Extensive stage SCLC patients receiving only first-line etoposide plus platinum chemotherapy will be enrolled in this cohort. Baseline tumor tissue samples and peripheral blood samples will be collected for transcriptome and immunohistochemistry analysis etc.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival	From the start of first-line treatment until disease progression or death due to any cause	2022.4.1-2023.12.31

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	From the start of first-line treatment until death due to any cause	2022.4.10-2024.12.31
Objective response rate	The tumor size was calculated by computed tomography or magnetic resonance Imaging scan, the best response was evaluated based on Response Evaluation Criteria in Solid Tumors (RECISTVersion1.1)	2022.4.10-2023.12.31
molecular subtyping and tumor microenvironment biomarkers	The molecular subtyping was carried out based on transcripsome sequencing following the method in published article PMID: 33482121, the tumor microenvironment biomarkers include tumor infiltrated immune cells and specific gene expression evaluated by transcripsome and Multiplex immunohistochemical analysis etc.	2022.4.10-2023.12.31

Collaborators and Investigators

• Sponsor: Peking University Cancer Hospital & Institute
• Investigators: Principal Investigator: Minglei Zhuo, Physician, Peking University Cancer Hospital & Institute

Study record dates

Study Major Dates

• Study Start (Actual): March 29, 2022
• Primary Completion (Actual): July 18, 2024
• Study Completion (Actual): December 1, 2024

Study Registration Dates

• First Submitted: June 24, 2023
• First Submitted That Met QC Criteria: July 3, 2023
• First Posted (Actual): July 6, 2023

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 10, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Small Cell Lung Carcinoma; Immunologic Factors; Physiological Effects of Drugs; Antibodies
• Other Study ID Numbers: 2021YJZ97

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No