Real-World Study on Gene Profile in Patients With Advanced NSCLC Who Progressed on First-Line Osimertinib Therapy(GPS).

Advanced NSCLC Clinical Trial

— GPS  

Official title:

Gene Profile in EGFRm Locally Advanced or Metastatic NSCLC Patients Post Osimertinib 1L Treatment Failure: A Real-world, Multi-center Study (GPS)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05219162
• Other study ID #: D5161R00037
• Status: Completed
• Phase: Phase 4
• Start date: February 25, 2022
• Est. completion date: May 9, 2024

Study information

• Verified date: May 2024
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Although some small sample studies have reported the possible resistance mechanisms of Osimertinib in the first-line treatment, it is still an urgent need to explore the whole gene profile in EGFRm advanced NSCLC patients post Osimertinib 1L treatment by paired tissue and plasma to guide subsequent treatment strategy. Thus, the gene profile post Osimertinib 1L treatment in tissue and plasma may help to guide the following treatment.

Participants will be required to provide paired tissue and whole blood after disease progression following 1L Osimertinib. 200 tissue samples and 200 whole blood samples will be used to detect gene alteration by NGS, respectively. 200 tissue samples will be used to detect pathological transformation by IHC. Approximately 80-100 tissue samples will be used to test MET overexpression by MET IHC and MET amplification by FISH respectively. Approximately 80-100 whole blood samples will be used to test MET amplification by ddPCR.

Description:

"Tumor tissue samples will be obtained by biopsy."

Recruitment information / eligibility

• Status: Completed
• Enrollment: 182
• Est. completion date: May 9, 2024
• Est. primary completion date: May 9, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria

Participants are eligible to be included in the study only if all of the following criteria apply:

Informed Consent

1. Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.

2. Provision of signed and dated, written informed consent form prior to any mandatory study-specific procedures, sampling, and analyses.

The ICF process is described in Appendix A3., Sex and Age

3. Male or female, age at least 18 years. Type of Participant and Disease Characteristics

4. Pathologically confirmed non-small cell lung cancer (NSCLC) with documented EGFR sensitive mutation (EGFR 19del and L858R) positive before Osimertinib 1L.

5. Locally advanced (clinical stage IIIB, IIIC) or metastatic NSCLC(clinical stage IVA or IVB) or recurrent NSCLC (per Version 8 of the International Association for the Study of Lung Cancer [IASLC] Staging Manual in Thoracic Oncology), not amenable to curative or radiotherapy (e.g., this may occur as systemic recurrence after prior surgery for early stage disease or patients may be newly diagnosed with stage IIIB/IV disease, which is at the start of Osimertinib therapy).

6. Patients must have been treated with Osimertinib as first line therapy until disease progression. Evidence of disease progression following 1L Osimertinib can be confirmed by investigators with criteria in Response Evaluation Criteria in Solid Tumours (RECIST) Version 1.1.

7. Agree to provide adequate tissue and whole blood for testing after disease progression following 1L Osimertinib.

Reproduction

8. Female participants who are not abstinent (in line with the preferred and usual lifestyle choice of the participant) and intend to be sexually active with a male partner must be using highly effective contraceptive measures, must not be breast feeding, and must have a negative pregnancy test prior to the enrolment or must have evidence of non-child-bearing potential by fulfilling 1 of the following criteria at screening:

• Post-menopausal, defined as more than 50 years of age and amenorrhoeic for at least 12 months following cessation of all exogenous hormonal treatments

• Women under 50 years old would be considered as postmenopausal if they have been amenorrhoeic for 12 months or more following cessation of exogenous hormonal treatments and have luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels in the post-menopausal range for the institution

• Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation.

Further information is available in Appendix E (Definition of Women of Childbearing Potential and Acceptable Contraceptive Methods).

9. Male participants must be willing to use barrier contraception. Exclusion Criteria

Participants are excluded from the study if any of the following criteria apply:

Medical Conditions

1. Any concurrent and/or other active malignancy that may affect tissue or whole blood testing results.

2. As judged by the investigator, any evidence of severe or uncontrolled systemic diseases, which in the investigator's opinion, makes it undesirable for the participant to participate in the study or that would jeopardise compliance with the protocol,. Screening for chronic conditions is not required.

Prior/Concomitant Therapy

3. Any concurrent anticancer treatment except local radiotherapy and radiotherapy for CNS metastasis. Concurrent use of hormonal therapy for non cancer related conditions (eg, hormone replacement therapy) is allowed.

Prior/Concurrent Clinical Study Experience 5 Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements.

Other Exclusions 6 Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).

7 In addition, the following are considered criteria for exclusion from the exploratory genetic research:

• Prior allogeneic bone marrow transplant

• Non-leukocyte depleted whole blood transfusion within 120 days of genetic sample collection.

Related Conditions & MeSH terms

• Advanced NSCLC
• Carcinoma, Non-Small-Cell Lung

Intervention

Genetic:
• Gene Profile explore
The tissue and blood sample for this genetic research will be obtained from the participants at baseline(disease progression after 1L Osimertinib). Paired tissue and whole blood sample should be collected per participant for genetics during the study.

Locations

Country	Name	City	State
China	Research Site	Beijing
China	Research Site	Changsha
China	Research Site	Chengdu
China	Research Site	Dalian
China	Research Site	Foshan
China	Research Site	Fuzhou
China	Research Site	Harbin
China	Research Site	Hefei
China	Research Site	Hefei
China	Research Site	Linhai
China	Research Site	Luoyang
China	Research Site	Rizhao
China	Research Site	Shanghai
China	Research Site	Taizhou
China	Research Site	Tianjin
China	Research Site	Zhengzhou

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Exploratory endpoints (In the case of sufficient tissue samples).	Prevalence of MET amplification by MET FISH	up to 2 weeks
Other	Exploratory endpoints (In the case of sufficient tissue samples)	Concordance of MET amplification between MET FISH testing and ddPCR blood testing	up to 2 weeks
Other	Exploratory endpoints (In the case of sufficient tissue samples)	Prevalence of MET overexpression by MET IHC testing.	up to 2 weeks
Other	Exploratory endpoints (In the case of sufficient tissue samples)	The overlap ratio of prevalence between MET amplification by FISH and MET overexpression by MET IHC	up to 2 weeks
Primary	Gene profile in tissue	? Gene profile in tissue Gene profile defined as gene alternation detected by NGS and frequency of every gene alternation.; All gene alterations include gene mutation, copy number variation(CNV), fusion, etc.; The frequency of all gene alteration detected by NGS(%) = (number of patients with every gene alteration detected by NGS)/(total number of patients in the FAS)×100%.	up to 2 weeks
Secondary	Gene profile in plasma	Gene profile defined as gene alternation detected by NGS and frequency of every gene alternation.	up to 2 weeks
Secondary	Concordance of plasma and tissue	Using selected representative genes (for example EGFR, MET, PIK3CA and etc.) to measure the concordance.	up to 2 weeks
Secondary	The percentage of pathology transformation	Pathology transformation is defined as those transformation from non-small-cell lung cancer to small-cell lung cancer or from adenocarcinoma to squamous carcinoma, can be observed by IHC	up to 2 weeks