EX VIVO DRUG RESPONSE PROFILING AND OUTCOME PREDICTION IN LUNG ADENOCARCINOMA

This observational study evaluates if ex-vivo lung cancer drug sensitivity testing results correlate with the driver mutations found by genetic sequencing and if it can predict treatment response.

Study Overview

• Status: Recruiting
• Conditions: Lung Adenocarcinoma; Malignant Pleural Effusions (Mpe)
• Intervention / Treatment: Other: Non-Interventional Study

Detailed Description

Non-small cell lung cancer (NSCLC) treatment decisions often rely on DNA sequencing, which only partially captures the tumor's mutational landscape and may miss other complex resistance mechanisms. Consequently, an unbiased functional drug screen is essential to rapidly identify optimal next-line therapies. Current drug sensitivity testing (DST) is limited by inefficient live tumor cells isolation. To address this, a rapid, unbiased DST platform utilizing FDA-approved targeted therapies was developed. Our approach uses malignant pleural effusions (MPEs) as a rich source of viable tumor cells. Because MPEs are highly heterogeneous, tumor cells are first identified via EpCAM flow cytometry, and the sample is enriched for tumor cells by depleting CD45+ immune cells using antibody-coated magnetic beads. These enriched tumor cells are then seeded into drug-containing plates. Following 72-hour incubation, cell viability is assessed using the CellTiter-Glo assay. Treatment efficacy is determined by the degree of reduction in cell viability at a range of drug concentrations, where the most effective treatment is the drug that reduces cell viability at the lowest concentration range.

To link clinical outcome and ex-vivo drug response assays, the investigators systematically measure drug sensitivity and resistance of primary tumor cells ex-vivo using a diverse compound library for individual patients in need of treatment. By systematically analyzing ex-vivo drug response patterns, tumors should be functionally grouped, by response phenotype. While for the purpose of this study selection of a specific treatment will not be based on ex-vivo drug response assays, clinical response- and follow-up data of patients will be prospectively collected in parallel.

• Study Type: Observational
• Enrollment (Estimated): 400

Contacts and Locations

Study Locations

• Israel
  • Ramat Gan, Israel, 5262100
    • Recruiting
    • Sheba Medical Center
    • Contact: Michael Peled, MD PhD; Phone Number: 972-3-5308420; Email: michael.peled@sheba.health.gov.il

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Patients with pleural effusion with a diagnosis of a lung cancer or suspected to be diagnosed with lung cancer according to their CT imaging, who are in need for pleural effusion drainage due to shortness of breath, and are willing to donate effusion for ex-vivo drug sensitivity testing.

Description

Inclusion Criteria:

• Presence of pleural effusion in patient with a diagnosis of a lung cancer or suspected to be diagnosed with lung cancer according to their CT imaging, who are in need for pleural effusion drainage due to shortness of breath, and are willing to donate effusion for ex-vivo drug sensitivity testing.
• Patient's written informed consent present.
• Ability to understand the nature of the trial and the trial related procedures and to comply with them.

Exclusion Criteria:

• negative cytology for malignancy in the last 6 months

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients with diagnosis of a Lung adenocarcinoma with the need of pleural drainage due to MPE	Other: Non-Interventional Study; Non-Interventional Study, patients go through pleural drainage due to shortness of breath

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Statistically significant correlation between patients' drug response by ex-vivo drug profiling and expected drug sensitivity according to genetic sequencing	Ex-vivo drug sensitivity categorizes drugs as sensitive/not sensitive. Results will be compared with the expected sensitivity of drugs according to the driver mutation found be genetic sequencing. For example, in EGFR-driven lung cancer, the tumor cells are expected to be more sensitive to EGFR-targeting drugs than to ALK-targeting drugs.	From enrollment until results of clinical genetic sequencing and drug sensitivity testing are obtained (within 3 weeks).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Accuracy of patients' drug response prediction by ex-vivo drug profiling	Ex-vivo drug sensitivity categorizes drugs as sensitive/not sensitive. Results will be compared with clinical outcome of patient (response vs. progressive disease as defined by RECISET score)	from date of enrollment until progression (latest 24 months)

Collaborators and Investigators

• Sponsor: Sheba Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): June 14, 2023
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): January 1, 2030

Study Registration Dates

• First Submitted: June 4, 2026
• First Submitted That Met QC Criteria: June 4, 2026
• First Posted (Actual): June 9, 2026

Study Record Updates

• Last Update Posted (Actual): June 9, 2026
• Last Update Submitted That Met QC Criteria: June 4, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Drug sensitivity testing, malignant pleural effusion, lung cancer
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Neoplasms by Histologic Type; Lung Diseases; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Respiratory Tract Neoplasms; Thoracic Neoplasms; Pleural Neoplasms; Carcinoma; Pleural Diseases; Pleural Effusion; Adenocarcinoma of Lung; Lung Neoplasms; Pleural Effusion, Malignant; Myeloproliferative Disorder, Chronic, with Eosinophilia
• Other Study ID Numbers: SHEBA-18-5494-MP-CTIL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No