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HER2 Positive OR TROP2 Positive Non-Small Cell Lung CancerNCT07610616

Study on the Mechanism of ADC Drug Evaluation Based on Immune Co-culture of Lung Cancer Organoids

An observational study of HER2 Positive OR TROP2 Positive Non-Small Cell Lung Cancer, run by Guangzhou Institute of Respiratory Disease at 1 site in China.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

A case-control study was conducted to evaluate the efficacy and mechanism of action of antibody-drug conjugates (ADCs) in lung cancer, utilizing patient-derived organoid (PDO)-immune co-cultures. Read more about this study

Who is it for?
Ages 18 to 100 years
What is being tested?
Antibody-drug conjugate (ADC) combination therapy
Type of treatment
Injection or infusion
How many people
10 participants
Where
1 siteChina
Study dates
28 Dec 2025to 1 Oct 2027
Phase
Observational
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 100 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Study population: Patients with a pathological diagnosis of non-small cell lung cancer (NSCLC), whose tumor patient-derived organoids (PDOs) exhibited strong or weak positive expression of the HER2 or TROP2 targets as determined by immunohistochemistry.

Who may be able to join

  • Age ≥ 18 years.
  • Availability of patient-derived organoids (PDOs) with matched autologous tumor-infiltrating lymphocytes (TILs) or peripheral blood mononuclear cells (PBMCs) from non-small cell lung cancer (NSCLC) cases.
  • Patients currently undergoing or scheduled to receive Trastuzumab deruxtecan (T-DXd) therapy who meet clinical eligibility criteria.
  • Provision of written informed consent.
  • PDOs exhibiting strong positive HER2 and TROP2 expression by immunohistochemistry (IHC) assigned to the experimental group.
  • PDOs exhibiting weak positive HER2 and TROP2 expression by IHC assigned to the negative control group.

Who cannot join

  • PDOs derived from patients with pathologically confirmed small cell lung cancer (SCLC).
  • Unavailability of matched autologous PDOs, TILs, or PBMCs.
  • Presence of any contraindications to T-DXd treatment.
  • Presence of other serious comorbidities resulting in an estimated survival of <3 months.
  • Pregnant or breastfeeding women.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Chengzhi Professor Zhou, PhD contact

13560351186

13560351186@163.com

Xinqing Lin, PhD contact

18819281507

linxinging81@163.com

China1 site, 1 recruiting
  • The First Affiliated Hospital of Guangzhou Medical University

    Guangzhou, Guangdong

    chengzhi Professor Zhou, PhD, 13560351186, 13560351186@163.com

    Xinqing Lin, PhD, 18819281507, linxinging81@163.com

    Recruiting

Other trials in China

About this study

A case-control study was conducted to evaluate the efficacy and mechanism of action of antibody-drug conjugates (ADCs) in lung cancer, utilizing patient-derived organoid (PDO)-immune co-cultures. Focusing on HER2-positive and TROP2-positive non-small cell lung cancer (NSCLC) cases, ADC candidates were screened for in vitro activity based on organoid-immune interaction models.

Key assessments included:

Read more

Tumor killing efficiency, assessed by dose-response relationships; Drug internalization (cellular uptake), as a measure of penetration into cancer cells; Antibody-dependent cellular cytotoxicity (ADCC) and bystander effect, with negative control targets employed to delineate specificity; Single-cell RNA sequencing, to profile transcriptional alterations at single-cell resolution.

Data demonstrated distinct ADC responses correlating with target expression and immune microenvironment features. The integrated approach provided cell-based evidence of ADC potency and revealed mechanistic insights-including immune-mediated cytotoxicity pathways and intracellular trafficking-supporting the rational design of clinical trials. These findings established a foundation for precision immunotherapy strategies and offered a mechanistic rationale for patient selection in HER2/TROP2-positive lung cancer.

Read the detailed description

A case-control study was conducted to systematically evaluate the therapeutic efficacy and underlying mechanisms of antibody-drug conjugates (ADCs) in non-small cell lung cancer (NSCLC), utilizing an integrated patient-derived organoid (PDO)-immune cell co-culture platform. Focusing on HER2-positive and TROP2-positive NSCLC cases, a comprehensive research pipeline was established, comprising three core components: the construction of a PDO-immune co-culture model, multidimensional tumor killing assessment, and mechanistic dissection of cellular internalization.

Clinically resected tumor tissues and malignant pleural effusion specimens were harvested to generate PDOs, which were rigorously validated for histological fidelity and phenotypic stability via H\&E staining and TTF-1 immunohistochemistry; cases were subsequently stratified based on HER2/TROP2 expression intensity. The functional integrity of the co-culture system was confirmed through flow cytometric analysis of immune cell purity and activation status, coupled with ELISA quantification of cytokines to verify effective immune-tumor crosstalk.

Pharmacodynamic evaluations were performed using ATP-based viability assays, PDO viability imaging, and Caspase-3/7 apoptosis detection. These assays simulated clinically relevant peak plasma concentrations (C max) to directly reflect in vivo drug exposure, while also assessing the synergistic potential of "ADC + Immuno-oncology" combination strategies to optimize clinical dosing regimens. Mechanistically, pHrodo dye tracking was employed to visualize and quantify cellular internalization and phagocytosis, complemented by single-cell RNA sequencing to delineate transcriptional profiles and identify specific subpopulations sensitive to ADC therapy. Furthermore, high-sensitivity Olink proteomics and multiplex fluorescence immunohistochemistry provided "cellular-molecular-spatial" evidence of immune activation and intracellular trafficking dynamics.

Collectively, the data revealed that distinct ADC responses correlated with target expression and the immune microenvironment, precisely characterizing the molecular signatures of sensitive cell subpopulations and their enhanced endocytic activity. These findings provide critical molecular targets and a theoretical basis for patient selection and the rational design of next-generation ADC therapies in HER2/TROP2-positive lung cancer.

Being tested
Antibody-drug conjugate (ADC) combination therapy
Keywords
Non-Small Cell Lung Cancer, HER2 Positive Non-Small Cell Lung Cancer, TROP2 Positive Non-Small Cell Lung Cancer
Medical subject headings
Carcinoma, Non-Small-Cell Lung

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Antibody-drug conjugate (ADC) combination therapyDrug

    Also called ADC + TKI/ICB + Cellular Therapy DS-8201, ADC + TKI/ICB + Cellular Therapy T-DM1, ADC + TKI/ICB + Cellular Therapy SG

    In a co-culture system of tumor patient-derived organoids (PDOs) and autologous immune cells, at least ten drug combinations comprising antibody-drug conjugates (ADCs) plus tyrosine kinase inhibitors (TKIs) or immune checkpoint blockers (ICBs) were employed to screen for ADCs with sensitivity against the tumor PDOs. The ADCs selected for evaluation included:

    Trastuzumab deruxtecan for injection (intravenous) Trastuzumab emtansine for injection (intravenous) Sacituzumab govitecan for injection (intravenous)

Study groups in NCT07610616
Study groupRoleWhat they receive
HER2 Positive OrTROP2 Positive non-small cell lung cancerThe abundance of HER2 or TROP2 target expression was determined by immunohistochemistry and categorized into strongly positive and weakly positive groups, representing the experimental group and negative control group, respectively. Using an immunococulture system based on patient-derived organoids, the in vitro activity of antibody-drug conjugates (ADCs)-including trastuzumab emtansine (an approved ADC administered intravenously)-that are either approved or currently in clinical trials was evaluated. In parallel, clinical patients provided ex vivo cytological assay results indicating their sensitivity to ADC therapy.
Receives: Drug: Antibody-drug conjugate (ADC) combination therapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Changes in ATP assay of tumor patient-derived organoids (PDOs) under treatment with ADCs and various drug combinations

    The single high-concentration ADC design was formulated to mimic the peak plasma concentration achieved after clinical administration, thereby directly reflecting the cytotoxic potency of the drug at effective concentrations. The combination therapy assessment focuses on the current trend of "ADC + immuno" strategies in oncology, providing ex vivo data to support optimization of clinical dosing regimens.

    Measured: Tumor viability assessed by luminescence measurement at 72 hours after co-culture with immune cells

  2. Real-time high-content imaging reveals efficient internalization of pHrodo-conjugated ADCs

    Kinetic analysis of ADC internalization was performed using a high-content imaging system. Briefly, cells were incubated with pHrodo-conjugated ADCs at 37°C. Real-time fluorescence imaging was conducted at 15-minute intervals for 24 hours to track the internalization efficiency. Quantitative data regarding cellular uptake were analyzed using the integrated high-content analysis software."

    Measured: 24hours

  3. Integrated analysis of ADC IC50 determination and scRNA-seq data post co-culture

    We observed a wide range of sensitivities to ADC treatment across different PDO models, as reflected by varying IC50 values (ranging from X nM to Y nM). To uncover the mechanistic basis for this heterogeneity, we performed scRNA-seq on tumor cells following the co-culture and ADC treatment. Unsupervised clustering revealed distinct tumor cell subpopulations, including a cluster characterized by high proliferative signature and another marked by stress-response pathways.

    Measured: 96hours

  4. Multiplex immunofluorescence (mIF) and high-sensitivity Olink proteomics for inflammatory cytokines.

    To characterize the immune landscape, we performed multiplex immunofluorescence (mIF) staining on tissue sections to analyze the spatial distribution of immune cells. Additionally, high-sensitivity Olink proteomics was utilized to quantify a panel of inflammatory cytokines in the culture supernatant.

    Measured: 96hours

Secondary outcomes (3)
  1. Fluorescence imaging of PDO viability and apoptosis assessment via caspase-3/7 activity in pharmaco-sensitivity and PDO-immune co-culture assays.

    We utilized fluorescent viability dyes to visualize the cytotoxic effects of ADCs in co-culture. Concurrently, caspase-3/7 cleavage was detected as a marker of intrinsic apoptosis induced by the drug payload.

    Measured: 96hours

  2. Cytokine secretion profiles (IL-6, TNF-α, IFN-γ) in co-culture supernatants measured by ELISA

    The levels of key effector cytokines, including IL-6, TNF-α, and IFN-γ, were quantified in the supernatant of the PDO-immune co-culture system using ELISA kits。

    Measured: 96hours

  3. Flow cytometric analysis of T cell activation and exhaustion markers in co-culture assays

    Cells harvested from co-cultures were stained with fluorophore-conjugated antibodies against surface markers. T cell activation was defined by the upregulation of CD69 and CD25, while T cell dysfunction was characterized by the expression of inhibitory receptors such as PD-1 and TIM-3.

    Measured: 96hours

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 May 2026
  2. Study start28 Dec 2025
  3. Primary completion1 Oct 2027 (estimated)
  4. Study completion1 Oct 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Case-control
Time perspective
Prospective
Enrolment
10 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07610616
Sponsor's protocol ID
ADC-2025-10-1
Status last verified
May 2026
First submitted
12 May 2026
Last updated
28 May 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Eltayeb E. Nance, Michael J. D. Gooden, Francesca M. Marcon; Antibody Fragments as Agonists and Antagonists in Cancer Therapy; Antibodies; 2023 Apr; 12; 72.

  • Hammood M, Craig AW, Leyton JV. Impact of Endocytosis Mechanisms for the Receptors Targeted by the Currently Approved Antibody-Drug Conjugates (ADCs)-A Necessity for Future ADC Research and Development. Pharmaceuticals (Basel). 2021 Jul 15;14(7):674. doi: 10.3390/ph14070674.

    PubMed 34358100
  • Fu Z, Li S, Han S, Shi C, Zhang Y. Antibody drug conjugate: the "biological missile" for targeted cancer therapy. Signal Transduct Target Ther. 2022 Mar 22;7(1):93. doi: 10.1038/s41392-022-00947-7.

    PubMed 35318309
  • Birrer MJ, Moore KN, Betella I, Bates RC. Antibody-Drug Conjugate-Based Therapeutics: State of the Science. J Natl Cancer Inst. 2019 Jun 1;111(6):538-549. doi: 10.1093/jnci/djz035.

    PubMed 30859213

Questions about this trial

What is this clinical trial studying?

An observational study of HER2 Positive OR TROP2 Positive Non-Small Cell Lung Cancer, run by Guangzhou Institute of Respiratory Disease at 1 site in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 28 May 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Chengzhi Professor Zhou, PhD (13560351186, 13560351186@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Changes in ATP assay of tumor patient-derived organoids (PDOs) under treatment with ADCs and various drug combinations (time frame: Tumor viability assessed by luminescence measurement at 72 hours after co-culture with immune cells). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07610616, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 May 2026.

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