Clinical trial NCT05219162: Real-World Study on Gene Profile in Patients With Advanced NSCLC Who Progressed on First-Line Osimertinib Therapy(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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Advanced NSCLC
Keywords: Advanced or metastatic non-small cell lung cancer
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2022-02-01
Enrollment: 182
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: 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.
Primary purpose: DIAGNOSTIC

Brief 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.

Detailed description: "Tumor tissue samples will be obtained by biopsy."

Eligibility criteria: 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.

Primary outcomes:
measure: Gene profile in tissue
timeFrame: up to 2 weeks
Secondary outcomes:
measure: Gene profile in plasma
timeFrame: up to 2 weeks
measure: Concordance of plasma and tissue
timeFrame: up to 2 weeks
measure: The percentage of pathology transformation
timeFrame: up to 2 weeks
Other outcomes:
measure: Exploratory endpoints (In the case of sufficient tissue samples).
timeFrame: up to 2 weeks
measure: Exploratory endpoints (In the case of sufficient tissue samples)
timeFrame: up to 2 weeks
measure: Exploratory endpoints (In the case of sufficient tissue samples)
timeFrame: up to 2 weeks
measure: Exploratory endpoints (In the case of sufficient tissue samples)
timeFrame: up to 2 weeks
Locations:
city: Beijing
country: China
facility: Research Site
city: Changsha
country: China
facility: Research Site
city: Chengdu
country: China
facility: Research Site
city: Dalian
country: China
facility: Research Site
city: Foshan
country: China
facility: Research Site
city: Fuzhou
country: China
facility: Research Site
city: Harbin
country: China
facility: Research Site
city: Hefei
country: China
facility: Research Site
city: Hefei
country: China
facility: Research Site
city: Linhai
country: China
facility: Research Site
city: Luoyang
country: China
facility: Research Site
city: Rizhao
country: China
facility: Research Site
city: Shanghai
country: China
facility: Research Site
city: Taizhou
country: China
facility: Research Site
city: Tianjin
country: China
facility: Research Site
city: Zhengzhou
country: China
facility: Research Site
Study officials:
affiliation: Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
name: Yuankai Shi, PhD
role: PRINCIPAL_INVESTIGATOR
References: