The HER Project: HRD in EGFR-mutated NSCLC

NCT07303218 | Active Not Recruiting

• 1 other identifier: The HER Project
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

This observational retrospective-prospective study aims to evaluate the prevalence of homologous recombination deficiency (HRD) in metastatic EGFR mutated NSCLC and to assess its correlation with clinical and molecular features. Based on the hypothesis that HRD identifies a distinct EGFRm subgroup with prognostic value and a potential sensitivity to PARP inhibitor-based strategies, translational analysis will be performed with multiple pre-clinical models, ranging from human cancer cells to murine models.

Conditions

EGFR; Non Small Cell Lung Cancer; Homologous Recombination Deficiency; PARP Inhibitor

Keywords

EGFR; Non small cell lung cancer; NSCLC; Homologous Recombination Deficiency; HRD; PARP Inhibitors; cell lines; organoids; Osimertinib; Olaparib; Genomic Scarring Score; TP53

Outcome Measures

Primary Outcomes (1)

• Prevalence of HRD in metastatic EGFRm NSCLC

  Proportion of EGFRm NSCLC with an HRD positive score evaluated by AmoyDx HRD Panel or similar (GSS ≥ 50).

  Baseline (T0), on diagnostic tumour sample

Secondary Outcomes (1)

• Correlation between HRD status and clinical outcomes and molecular features

  Up to 3 years of follow-up for PFS/OS; baseline for clinical and molecular characteristics.

Study Arms (2)

Retrospective Cohort

Patients with metastatic EGFR-mutated NSCLC diagnosed and treated between January 2020 and September 2025, with tumour tissue available for HRD analysis.

Other: No Intervention: Observational Cohort

Prospective Cohort

Patients with newly diagnosed metastatic EGFR-mutated NSCLC, with baseline tumour tissue available for HRD testing and prospectively collected clinical follow-up.

Other: No Intervention: Observational Cohort

Interventions

No Intervention: Observational Cohort OTHER

Observational study only; participants receive standard-of-care treatments not assigned by the study

Prospective Cohort; Retrospective Cohort

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Adult patients (≥18 years) with metastatic EGFR-mutated NSCLC eligible for treatment with EGFR-TKI according to standard clinical practice, with available tumor tissue suitable for HRD testing

You may qualify if:

• Participant is willing and able to give informed consent for participation in the study. However, since a part of the study is retrospective and, considering the large sample sizes required and considering that the disease involved in this study affects elderly subjects with co-morbidities and presents a significant mortality rate based on the stage of the disease, deceased and untraceable patients will also be included.
• Age ≥18 years old
• Have a metastatic histologically confirmed NSCLC
• Presence of EGFR common mutations (i.e. ex19del and L858R)
• Have sufficient biological material to assess genomic profiling with AmoyDx Focus panel or similar
• Clinical data available

You may not qualify if:

• Insufficient baseline tumour tissue (unsuitable for HRD scoring)
• Presence of EGFR uncommon mutations (i.e. ex20ins)
• Known presence of co-occurring uncommon EGFRm, ALK, ROS1, or other main oncogenic drivers.

Sponsors & Collaborators

• IRCCS San Raffaele: lead

Study Sites (1)

Dept. Medical Oncology

Milan, MI, 20132, Italy

Location

Related Publications (26)

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Biospecimen

Retention: SAMPLES WITH DNA

Tumor samples (biopsies, surgical samples)

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Francesca Rita Ogliari, Medical Doctor

  IRCCS Ospedale San Raffaele

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Doctor

Study Record Dates

• First Submitted: December 11, 2025
• First Posted: December 24, 2025
• Study Start: December 1, 2025
• Primary Completion (Estimated): December 31, 2029
• Study Completion (Estimated): December 31, 2032
• Last Updated: December 31, 2025

Record last verified: 2025-12

Locations

IT (1)