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NCT Number: NCT07207278

Multi Omics Molecular Characteristics and Immunophenotyping of Lung Signet Ring Cell Carcinoma

This study aims to reveal the molecular characteristics and immune microenvironmental profile of signet ring cell carcinoma of the lung (LSRCC) in the Chinese population through integrated multi-omics analyses. The project plans to enroll formalin-fixed paraffin-embedded (FFPE) tissue samples and paired adjacent tissues from 39 patients with previously untreated LSRCC to establish a Chinese LSRCC molecular database. Whole-exome sequencing (WES) will be used to analyze gene mutations, such as single nucleotide variants (SNVs), copy number variants (CNVs), and fusion events. RNA-seq will be used to screen for differentially expressed genes (DEGs) and perform immunophenotyping, while multiplex immunohistochemistry will be employed to quantify the tumor immune microenvironment (TIME). The successful implementation of this project is expected to identify novel molecular biomarkers specific to the Chinese LSRCC population, enhance understanding of the unique immune phenotypes within this group, and-combined with clinical follow-up-establish correlations between molecular/immune signatures and therapeutic efficacy assessments, thereby providing evidence-based medical support for subsequent personalized precision diagnosis and treatment of LSRCC in this population.

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Key information

Age range

18 year–85 year

Sex eligibility

All sexes

Study type

Observational

Primary location

Centre of Translational Medicine, Affiliated Hangzhou First People's Hospital, Westlake University School of Medicine

Hangzhou, Zhejiang, 310006, China

Location status: Recruiting

Location contact

Shirong Zhang

CONTACT

[email protected]

+86-0571-56007664

About this study

This study aims to reveal the molecular characteristics and immune microenvironmental profile of signet ring cell carcinoma of the lung (LSRCC) in the Chinese population through integrated multi-omics analyses. The project plans to enroll formalin-fixed paraffin-embedded (FFPE) tissue samples and paired adjacent tissues from 39 patients with previously untreated LSRCC to establish a Chinese LSRCC molecular database. Whole-exome sequencing (WES) will be used to analyze gene mutations, including single nucleotide variants (SNVs), copy number variants (CNVs), and fusion events. RNA-seq will be utilized to screen for differentially expressed genes (DEGs) and conduct immunophenotyping, while multiplex immunohistochemistry will be applied to quantify the tumor immune microenvironment (TIME). The successful implementation of this project is expected to identify novel molecular biomarkers specific to the Chinese LSRCC population, enhance understanding of the unique immune phenotypes within this group, and-combined with clinical follow-up-establish correlations between molecular/immune signatures and therapeutic efficacy assessments, thereby providing evidence-based medical support for subsequent personalized precision diagnosis and treatment of LSRCC in this population.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

1.Histologically confirmed, previously untreated LSRCC; 2. Adequate FFPE tumor tissue and paired adjacent non-tumor tissue available; 3. Expected survival ≥ 12 weeks; 4. Patients (or their legal guardians) willing and able to provide written informed consent; 5.Availability of complete pathology and imaging data.

Exclusion criteria

  • Prior systemic anticancer therapy; 2. Secondary LSRCC (i.e., metastatic signet ring cell carcinoma originating from a non-lung primary site); 3. Concurrent other malignancies; 4. Incomplete pathology results, missing imaging data, or unreliable follow-up information; 5. Pregnancy or lactation

Treatment and study plan

Patients with specific TIME subtype and ALK fusion mutations (confirmed via RNA-seq and OncoKB annotation) will receive tyrosine kinase inhibitors (TKIs, e.g., alectinib or crizotinib) as first-line

Drug

Patients with specific TIME subtype and ALK fusion mutations (confirmed via RNA-seq and OncoKB annotation) will receive tyrosine kinase inhibitors (TKIs, e.g., alectinib or crizotinib) as first-line therapy. Clinical response will be assessed via RECIST v1.1 criteria using serial CT imaging (baseline, 8 weeks, and every 12 weeks thereafter). Correlative analyses will evaluate TKI efficacy in relation to TIME subtype, ALK fusion variant, and multi-omic signatures.

Primary outcomes

  1. Week 8 Objective Response Rate (ORR) by RECIST v1.1 in ALK Fusion-Positive LSRCC Patients with Hybrid TIME Subtype

    Time frame: 8 weeks

    Objective Response Rate (ORR), defined as the proportion of patients achieving Complete Response (CR) or Partial Response (PR) per RECIST v1.1 criteria, assessed via contrast-enhanced CT at Week 8 following initiation of TKI therapy.

Secondary outcomes

  1. Progression-Free Survival (PFS)

    Time frame: From baseline until disease progression or death (assessed up to 24 months).

    Time from initiation of TKI therapy to the first documented radiologic disease progression (as per RECIST v1.1) or death from any cause, whichever occurs first.

  2. Overall Survival (OS)

    Time frame: From baseline until death from any cause (assessed up to 36 months).

    Time from initiation of TKI therapy to death from any cause.

  3. Duration of Response (DoR)

    Time frame: From first response until progression or death (assessed up to 24 months).

    Among patients who achieve an objective response (CR or PR), the time from the first documented response to disease progression or death from any cause.

  4. Disease Control Rate (DCR) at Week 8

    Time frame: 8 weeks

    Proportion of patients achieving Complete Response (CR), Partial Response (PR), or Stable Disease (SD) per RECIST v1.1 at Week 8.

  5. Safety and Tolerability of TKI Therapy

    Time frame: From initiation of TKI therapy until 30 days after the last dose (assessed up to 24 months).

    Incidence and severity of adverse events, laboratory abnormalities, and dose modifications, graded according to NCI-CTCAE version 5.0.

  6. Concordance Between Baseline mIHC-Defined TIME Subtypes and Treatment Outcomes

    Time frame: From baseline until disease progression or death (assessed up to 24 months).

    Agreement between baseline multiplex immunohistochemistry (mIHC)-defined TIME subtypes (I, II, III) and real-world treatment outcomes (ORR and PFS) across the full cohort.

Study contacts

Contact information is provided by the study sponsor or research team.

Shirong Zhang

CONTACT

[email protected]

+86-0571-56007664

Sponsors and collaborators

Lead sponsor

First People's Hospital of Hangzhou

Other

Collaborators

  • General Hospital of Ningxia Medical University
  • Zhejiang University

Registry information

Important dates

Study start
2025
Primary completion
2027
Study completion
2027
First posted
Oct 3, 2025
Registry last updated
Oct 3, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.