Advanced NSCLC
Conditions
Keywords
Advanced or metastatic non-small cell lung cancer
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.
Interventions
GENETICGene 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.
Sponsors
AstraZeneca
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 86 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Gene Alterations inTissue Detected by NGS | At enrollment | The Percentage of gene alteration detected by NGS(%) = (number of patients with gene alteration detected by NGS)/(total number of patients in the FAS)×100%. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| EGFR Sensitivity of Plasma and Tissue | At enrollment | Tissue sample was the reference standard. -sensitivity=(number of patients with positive result in both plasma and tissue)/(total number of patients with positive result in tissue samples)×100% |
| EGFR Specificity of Plasma and Tissue | At enrollment | Tissue sample was the reference standard. \- specificity=(number of patients with negative result in both plasma and tissue)/(total number of patients with negative result in tissue samples)×100%. |
| Percentage of Participants With Gene Alterations in Plasma Detected by NGS | At enrollment | The percentage of gene alteration detected by NGS(%) = (number of patients with gene alteration detected by NGS)/(total number of patients in the FAS)×100%. |
| EGFR NPV of Plasma and Tissue | At enrollment | Tissue sample was the reference standard. \- NPV (%)=(number of patients with negative result in both plasma and tissue)/(total number of patients with negative result in plasma samples)×100%. |
| The Percentage of Pathology Transformation | At enrollment | Pathology transformation was 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 Proportion of pathology transformation(%) = (number of patients with pathology transformation)/(total number of patients in the FAS)×100%. |
| EGFR PPV of Plasma and Tissue | At enrollment | Tissue sample was the reference standard. PPV (%)=(number of patients with positive result in both plasma and tissue)/(total number of patients with positive result in plasma samples)×100% |
Countries
China
Participant flow
Recruitment details
The study screened the first participant on 25 February 2022 and the last participant's last visit was completed on 29 April 2024. A total of 183 participants were screened (signed ICF), among which, 182 participants (99.5%) were successfully enrolled into the study from 16 study sites in China
Pre-assignment details
Among the 183 screened (signed ICF) participants, 182 of them (99.5%) successfully enrolled in the study (fulfilled eligibility criteria at screening), while only 1 participant (0.5%) did not meet the inclusion criteria. A total of 149 subjects who had valid gene data from both plasma and tissue were included in the Full Analysis Set (FAS), which will be the primary analysis set for all analyses.
Participants by arm
| Arm | Count |
|---|---|
| Patients With EGFR Negative Result in Plasma Samples patients with EGFR negative result in plasma samples | 149 |
| Total | 149 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Meet exclusion criterion or did not meet inclusion criteria | 6 |
| Overall Study | Withdrawal by Subject | 23 |
Baseline characteristics
| Characteristic | Patients With EGFR Negative Result in Plasma Samples |
|---|---|
| Age, Continuous Age(years) | 62.3 years STANDARD_DEVIATION 9.98 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 149 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Sex: Female, Male Sex Female | 84 Participants |
| Sex: Female, Male Sex Male | 65 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 0 |
| other Total, other adverse events | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 |
Outcome results
Primary
Percentage of Participants With Gene Alterations inTissue Detected by NGS
The Percentage of gene alteration detected by NGS(%) = (number of patients with gene alteration detected by NGS)/(total number of patients in the FAS)×100%.
Time frame: At enrollment
Population: 149 subjects who had valid gene data from both plasma and tissue were included in the analysis.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Post Osimertinib 1L Treatment | Percentage of Participants With Gene Alterations inTissue Detected by NGS | EGFR | 139 Participants |
| Post Osimertinib 1L Treatment | Percentage of Participants With Gene Alterations inTissue Detected by NGS | TP53 | 106 Participants |
| Post Osimertinib 1L Treatment | Percentage of Participants With Gene Alterations inTissue Detected by NGS | MET | 47 Participants |
Secondary
EGFR NPV of Plasma and Tissue
Tissue sample was the reference standard. \- NPV (%)=(number of patients with negative result in both plasma and tissue)/(total number of patients with negative result in plasma samples)×100%.
Time frame: At enrollment
Population: 34 patients with negative result in plasma samples
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Post Osimertinib 1L Treatment | EGFR NPV of Plasma and Tissue | 8 Participants |
Secondary
EGFR PPV of Plasma and Tissue
Tissue sample was the reference standard. PPV (%)=(number of patients with positive result in both plasma and tissue)/(total number of patients with positive result in plasma samples)×100%
Time frame: At enrollment
Population: 115 patients with positive result in plasma samples
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Post Osimertinib 1L Treatment | EGFR PPV of Plasma and Tissue | 113 Participants |
Secondary
EGFR Sensitivity of Plasma and Tissue
Tissue sample was the reference standard. -sensitivity=(number of patients with positive result in both plasma and tissue)/(total number of patients with positive result in tissue samples)×100%
Time frame: At enrollment
Population: 139 Patients with EGFR positive in tissue
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Post Osimertinib 1L Treatment | EGFR Sensitivity of Plasma and Tissue | 113 Participants |
Secondary
EGFR Specificity of Plasma and Tissue
Tissue sample was the reference standard. \- specificity=(number of patients with negative result in both plasma and tissue)/(total number of patients with negative result in tissue samples)×100%.
Time frame: At enrollment
Population: 10 patients with negative result in tissue samples
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Post Osimertinib 1L Treatment | EGFR Specificity of Plasma and Tissue | 8 Participants |
Secondary
Percentage of Participants With Gene Alterations in Plasma Detected by NGS
The percentage of gene alteration detected by NGS(%) = (number of patients with gene alteration detected by NGS)/(total number of patients in the FAS)×100%.
Time frame: At enrollment
Population: 149 subjects who had valid gene data from both plasma and tissue were included in the analysis.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Post Osimertinib 1L Treatment | Percentage of Participants With Gene Alterations in Plasma Detected by NGS | EGFR | 115 Participants |
| Post Osimertinib 1L Treatment | Percentage of Participants With Gene Alterations in Plasma Detected by NGS | TP53 | 65 Participants |
| Post Osimertinib 1L Treatment | Percentage of Participants With Gene Alterations in Plasma Detected by NGS | MET | 14 Participants |
Secondary
The Percentage of Pathology Transformation
Pathology transformation was 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 Proportion of pathology transformation(%) = (number of patients with pathology transformation)/(total number of patients in the FAS)×100%.
Time frame: At enrollment
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Post Osimertinib 1L Treatment | The Percentage of Pathology Transformation | Non-small-cell lung cancer to small-cell lung cancer | 2 Participants |
| Post Osimertinib 1L Treatment | The Percentage of Pathology Transformation | Adenocarcinoma to squamous carcinoma | 2 Participants |