Clinical trial NCT06863818: Overcoming Resistance to EGFR Neutralization by Combination of Monoclonal Antibodies and Novel Cancer Drugs
Official title: Overcoming Resistance to EGFR Neutralization by Combination of Monoclonal Antibodies and Novel Cancer Drugs (Superamento Della Resistenza Alla Neutralizzazione di EGFR Nel Trattamento Con Anticorpi Monoclonali e Nuovi Farmaci Oncologici)
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Non Small Cell Lung Cancer
Keywords: EGFR mutation
Lead sponsor: IRCCS Azienda Ospedaliero-Universitaria di Bologna
Sponsor class: OTHER
First posted: 2025-03-07
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients who have EGFR receptor amplification/overexpression or activating mutations, either responsive to anti-EGFR therapy (TKIs or mABs) or recurrent despite anti-EGFR therapy (TKIs or mABs), will be enrolled in the study.

Brief summary: The study is aimed at patients with advanced cancer and EGFR mutation. Some molecules recently discovered at the level of tumor tissue can influence the response to anti-EGFR drugs. Among these molecules is NRG1, which binds to the EGFR receptor family.

Unravelling the mechanisms that give cancer cells resistance to such biologics could improve response to therapy and survival. And analyzing tumors during anti-EGFR drug therapy used in clinical practice could allow us to perform analyses on NRG1 and hypothesize a possible strategy to increase survival

Detailed description: Experimental, tissue study. Patients with EGFR receptor amplification/overexpression or activating mutations treated with anti-EGFR cancer therapies will be involved in the study as required in normal clinical practice. Clinical information of the patients, relevant to the conduct of the study, will be collected: age, sex, ethnicity, smoking habit, diagnosis, staging of the tumor, site of any metastases, possible presence of ascites and/or pleural effusion, type of oncological therapy administered, concomitant therapies, radiological re-evaluation of the tumor, response to treatment, survival.

Similarly, peripheral blood, tissue obtained from archival tumor biopsies, ascitic and/or pleural fluid samples (taken, if present, as per clinical practice) will be collected. Primary cell cultures will be derived from tumor biopsies, ascites, and/or pleural effusion for in vitro studies The lymphocyte population will be isolated from the peripheral blood of patients

Eligibility criteria: Inclusion Criteria:

* patients aged ≥ 18 years
* patients with advanced cancer characterized by amplification/overexpression or activating mutations of the EGFR receptor.
* patients who are candidates for treatment with TKI and/or mAbs both in the first and second line, according to clinical practice.
* possibility of obtaining all information relating to the clinical history - obtaining written informed consent

Exclusion Criteria:

* Patients who in the opinion of the investigator may not be compliant with the needs of the study
* patients suffering from pathologies (e.g. psychiatric, neurological) that do not allow the obtaining of valid informed consent

Primary outcomes:
measure: To evaluate in vitro the molecular mechanisms that regulate the expression of NRG1 and/or IL-1 in relation to ERBB family receptors (EGFR, HER2, HER3 and HER4) before and after the standard therapy resistance phase in patients with mutation in
timeFrame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months
Secondary outcomes:
measure: To evaluate the response to TKIs and/or mAbs of isolated tumor tissue before and after the resistance phase to standard therapy in patients with EGFR mutation and propagated in vitro, in the presence of the lymphocyte component (T lymphocytes). The devel
timeFrame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months
Other outcomes:
Locations:
city: Bologna
country: Italy
facility: IRCCS Azienda Ospedaliero-Universitaria di Bologna
Study officials:
affiliation: IRCCS Azienda Ospedaliero-Universitaria di Bologna
name: Andrea Ardizzoni, MD
role: PRINCIPAL_INVESTIGATOR
References: