Clinical Trials List
Protocol NumberGO29437
NCT Number(ClinicalTrials.gov Identfier)NCT02367794
2015-07-01 - 2019-12-16
Phase III
Terminated13
ICD-10C34.90
Malignant neoplasm of unspecified part of unspecified bronchus or lung
A Phase III, Open-Label, Multicenter, Randomized Study Evaluating The Efficacy And Safety Of MPDL3280A (Anti-PD-L1 Antibody) In Combination With Carboplatin + Paclitaxel Or MPDL3280A In Combination With Carboplatin + Nab-Paclitaxel Versus Carboplatin + Nab-Paclitaxel In Chemotherapy-Naïve Patients With Stage IV Squamous Non-Small Cell Lung Cancer
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Trial Applicant
PPD DEVELOPMENT (HK) LIMITED
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Sponsor
F. Hoffmann-La Roche Ltd
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- Shah-Hwa Chou Division of Thoracic Surgery
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Terminated
The Actual Total Number of Participants Enrolled
0 Terminated
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- 廖唯昱 Division of Thoracic Medicine
- Jih-Hsiang Lee Division of Hematology & Oncology
- 陳冠宇 Division of Thoracic Medicine
- 林育麟 Division of Hematology & Oncology
- 許嘉林 Division of Thoracic Medicine
- CHAO-CHI HO CHAO-CHI HO Division of Thoracic Medicine
- Chia-Chi Lin Division of Hematology & Oncology
- JIN-YUAN SHIH Division of Thoracic Medicine
- James Chih-Hsin Yang Division of Hematology & Oncology
- 張逸良 Division of Others
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- 廖偉志 Division of Thoracic Medicine
- 陳鴻仁 Division of Thoracic Medicine
- Chen Chia-Hung Division of Thoracic Medicine
- Chih-Yen Tu Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
0 Terminated
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- 謝任富 Division of Radiology
- Chih-Hung Chen Division of Hematology & Oncology
- 莊立邦 Division of Hematology & Oncology
- 黃世豪 Division of Hematology & Oncology
- Cheng-Ta Yang Division of Hematology & Oncology
- 枋岳甫 Division of Hematology & Oncology
- Shih-Hong Li Division of Hematology & Oncology
- Wen-Cheng Chang Division of Hematology & Oncology
- 林定佑 Division of Hematology & Oncology
- 李忠恕 Division of Hematology & Oncology
- Chih-Liang Wang Division of Hematology & Oncology
- Shih-Wei Lin Division of Hematology & Oncology
- 林倡葦 Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- YEN-HAN TSENG Division of Thoracic Medicine
- Jen-Fu Shih Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- KUO-HSUAN HSU Division of Thoracic Medicine
- TSUNG -YING YANG Division of Thoracic Medicine
- 陳焜結 Division of Thoracic Medicine
- JENG-SEN TSENG Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
0 Terminated
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- 蕭丞皓 Division of Thoracic Surgery
The Actual Total Number of Participants Enrolled
0 Terminated
Condition/Disease
Squamous Non-Small Cell Lung Cancer
Objectives
A Phase III, Open-Label, Multicenter, Randomized Study Evaluating The Efficacy And Safety Of MPDL3280A (Anti-PD-L1 Antibody) In Combination With Carboplatin + Paclitaxel Or MPDL3280A In Combination With Carboplatin + Nab-Paclitaxel Versus Carboplatin + Nab-Paclitaxel In Chemotherapy-Naïve Patients With Stage IV Squamous Non-Small Cell Lung Cancer
Test Drug
MPDL3280A
Active Ingredient
MPDL3280A
Dosage Form
IV
Dosage
60mg/mL
Endpoints
Curative effect goal
The common main goals of this experiment are as follows:
To evaluate the efficacy of atezolizumab, the measurement method is the trial host. According to the solid tumor efficacy evaluation standard version 1.1 (RECIST v1.1), the tumor gene expression (tGE) population and the intention to treat (ITT) population are evaluated for disease-free survival (PFS)
To evaluate the efficacy of atezolizumab, the measurement method is the overall survival (OS) of the intent-to-treat (ITT) population
The common main goals of this experiment are as follows:
To evaluate the efficacy of atezolizumab, the measurement method is the trial host. According to the solid tumor efficacy evaluation standard version 1.1 (RECIST v1.1), the tumor gene expression (tGE) population and the intention to treat (ITT) population are evaluated for disease-free survival (PFS)
To evaluate the efficacy of atezolizumab, the measurement method is the overall survival (OS) of the intent-to-treat (ITT) population
Inclution Criteria
Inclusion conditions
Patients must meet all of the following conditions to be included in this trial:
1. Sign the subject consent form
2. Male or female who is over 18 years old (patients participating in this trial in Taiwan must be over 20 years old)
3. United States East Coast Cancer Clinical Research Cooperative (ECOG) physical status 0 or 1.
4. Stage 4 squamous non-small cell lung cancer confirmed by histology or cytology (according to the seventh edition of the Union International Cancer Center/American Joint Committee on Cancer staging system; Detterbeck et al., 2009)
If the main histology is shown to be squamous, patients with mixed histology (squamous and non-squamous) may be eligible.
5. Have not received treatment for stage IV squamous non-small cell lung cancer.
- Patients with known epidermal growth factor receptor (EGFR) gene sensitivity mutations must have experienced disease progression (during or after treatment), or received one or more EGFR TKIs (e.g. erlotinib), Gefitinib) or another EGFR tyrosine agonist inhibitor (TKI) suitable for the treatment of EGFR mutant non-small cell lung cancer. Patients with unknown EGFR mutation status do not need to be tested.
- Patients with known ALK fusion oncogenes must have experienced disease progression (during or after treatment), or patients with ALK fusion oncogenes must receive one or more types of drugs suitable for the treatment of non-small cell lung cancer An intolerable condition occurs after ALK inhibitor drugs (crizotinib). Patients with unknown ALK mutation status do not need to be tested.
6. If the patient has received new adjuvant therapy, adjuvant chemotherapy, radiotherapy or chemoradiation therapy for curing non-metastatic diseases, the patient must pass between the latest chemotherapy, radiotherapy or chemoradiation therapy and random assignment. A treatment-free period of at least 6 months.
7. Patients with a history of asymptomatic central nervous system (CNS) metastasis are considered eligible, provided that the following conditions are met:
- Only allow metastasis to the cerebellum and supratentorial brain (ie no metastasis of midbrain, pons, medulla oblongata or spinal cord)
- Currently there is no need to use corticosteroids to treat central nervous system diseases. If you have not received stereotactic radiotherapy within 7 days before random assignment, whole brain radiation is within 14 days
�{ No evidence of interim progress during the completion of CNS-directed therapy and screening radiology trials.
When a new asymptomatic CNS metastasis is found by a screening scan, the patient must receive radiotherapy and/or surgery for the CNS metastasis. After treatment, if these patients meet all other conditions, they may be eligible without additional brain scans before randomization.
8. The central laboratory will perform IHC (immunohistochemical staining) tests on the previously obtained archived tumor tissues or biopsies at the time of screening to determine the known PD-L1 tumor status
- To participate in this trial, a typical formalin-fixed paraffin-embedded (FFPE) paraffin block of tumor specimens (recommended) or 15 (or more) unstained serial sections freshly cut from FFPE tumor specimens are required Slides. If fewer than 15 slides (but not less than 10) are available during the base period, the patient may still be eligible after discussion with the medical monitor. This specimen must be accompanied by a relevant pathology report.
- Fine needle aspiration (defined as unpreserved tissue structure and used as a sample for cell suspension and/or cell smear), brushing or sedimentation of cells (for example: taken from pleural effusion and Lavage specimens) are not accepted.
- Tumor tissues taken from bone metastases after decalcification are not accepted.
- For thick needle biopsies, it is recommended that at least three thick needle specimens be embedded in a single paraffin block and sent for evaluation.
9. According to RECIST (Solid Tumor Response Evaluation Criteria) Version 1.1, it is defined as a measurable disease
- A lesion that has received radiation is regarded as a measurable disease when it has been clearly recorded that the disease has deteriorated since radiation therapy and the lesion that has received radiation is not the only disease site.
10. The following test results were obtained within 14 days before random assignment, which showed that blood and peripheral organs were adequate:
- Absolute Neutrophil Count (ANC) d 1500, no granulocyte colony stimulating factor support (without granulocyte colony stimulating factor support)
- Lymphocyte count d 500
- Platelet count d 100,000 (without blood transfusion)
- Heme d 9.0 g/dL
Patients can meet this condition by receiving blood transfusions.
- International Normalized Ratio (INR) or Partial Coagulation Time (aPTT) & T1.5 times the upper limit of normal (ULN)
This condition is only applicable to those who have not received anticoagulation therapy, and patients receiving anticoagulation therapy should maintain a stable dose.
- Aspartic acid transamination (AST), Alanine transamination (ALT) and alkaline phosphate T2.5 times the upper limit of normal , With the following exceptions:
Patients with known liver metastases: AST and/or ALT T5 times the upper limit of normal
Cases showing patients with liver or bone cancer metastasis: alkaline phosphate T5 times the upper limit of normal.
- Serum bilirubin T1.25 times the upper limit of normal
Patients with known Gilbert's disease and serum bilirubin T3 times the upper limit of normal can be included in the trial.
- Serum creatinine T 1.5 times the upper limit of normal.
11. For female patients with fertility, it should be agreed (by the patient and/or their partner) to adopt a contraceptive method that is highly effective and continues to be used in the correct way, with a very low failure rate (<1% per year). After receiving the last dose of atezolizumab, continue to use this contraceptive method for 5 months, and continue to use this method for 30 days after the last dose of nanogranular albumin paclitaxel (nab-paclitaxel), or after receiving the last dose of paclitaxel (paclitaxel). ) 6 months later, whichever is later.
For male patients with female partners who are fertile, it should be agreed (by the patient and/or their partner) to adopt a highly effective method, and when used continuously in the correct way, the failure rate is very low (every year 1%), and continue to use the last dose of nanogranular albumin paclitaxel (nab-paclitaxel), paclitaxel (paclitaxel) and/or carboplatin for 6 months. Such methods include: compound (contains estrogen and progesterone) oral contraceptives, oral contraceptives containing only progesterone to inhibit ovulation combined with another barrier method containing spermicide, intrauterine contraceptive device (IUD): intrauterine Dosage system (IUS), bilateral tubal ligation or partner vasectomy (with the knowledge that there is only one partner for the entire trial period), and abstinence. Men must avoid sperm donation during the trial period and 6 months after the last dose of nab-paclitaxel, paclitaxel and/or carboplatin, whichever is later .
12. Oral contraceptives must be combined with other contraceptive methods, because oral contraceptives may have potential interactions with test drugs. If the partner of a male patient participating in this clinical trial is fertile, the same rules apply to male patients participating in this clinical trial. Male patients must use condoms.
13. Women who have not been menopausal (non-treatment-induced amenorrhea lasting d12 months) or surgically sterilized within 14 days before starting to use the test drug must undergo a serum pregnancy test to obtain a negative result.
Patients must meet all of the following conditions to be included in this trial:
1. Sign the subject consent form
2. Male or female who is over 18 years old (patients participating in this trial in Taiwan must be over 20 years old)
3. United States East Coast Cancer Clinical Research Cooperative (ECOG) physical status 0 or 1.
4. Stage 4 squamous non-small cell lung cancer confirmed by histology or cytology (according to the seventh edition of the Union International Cancer Center/American Joint Committee on Cancer staging system; Detterbeck et al., 2009)
If the main histology is shown to be squamous, patients with mixed histology (squamous and non-squamous) may be eligible.
5. Have not received treatment for stage IV squamous non-small cell lung cancer.
- Patients with known epidermal growth factor receptor (EGFR) gene sensitivity mutations must have experienced disease progression (during or after treatment), or received one or more EGFR TKIs (e.g. erlotinib), Gefitinib) or another EGFR tyrosine agonist inhibitor (TKI) suitable for the treatment of EGFR mutant non-small cell lung cancer. Patients with unknown EGFR mutation status do not need to be tested.
- Patients with known ALK fusion oncogenes must have experienced disease progression (during or after treatment), or patients with ALK fusion oncogenes must receive one or more types of drugs suitable for the treatment of non-small cell lung cancer An intolerable condition occurs after ALK inhibitor drugs (crizotinib). Patients with unknown ALK mutation status do not need to be tested.
6. If the patient has received new adjuvant therapy, adjuvant chemotherapy, radiotherapy or chemoradiation therapy for curing non-metastatic diseases, the patient must pass between the latest chemotherapy, radiotherapy or chemoradiation therapy and random assignment. A treatment-free period of at least 6 months.
7. Patients with a history of asymptomatic central nervous system (CNS) metastasis are considered eligible, provided that the following conditions are met:
- Only allow metastasis to the cerebellum and supratentorial brain (ie no metastasis of midbrain, pons, medulla oblongata or spinal cord)
- Currently there is no need to use corticosteroids to treat central nervous system diseases. If you have not received stereotactic radiotherapy within 7 days before random assignment, whole brain radiation is within 14 days
�{ No evidence of interim progress during the completion of CNS-directed therapy and screening radiology trials.
When a new asymptomatic CNS metastasis is found by a screening scan, the patient must receive radiotherapy and/or surgery for the CNS metastasis. After treatment, if these patients meet all other conditions, they may be eligible without additional brain scans before randomization.
8. The central laboratory will perform IHC (immunohistochemical staining) tests on the previously obtained archived tumor tissues or biopsies at the time of screening to determine the known PD-L1 tumor status
- To participate in this trial, a typical formalin-fixed paraffin-embedded (FFPE) paraffin block of tumor specimens (recommended) or 15 (or more) unstained serial sections freshly cut from FFPE tumor specimens are required Slides. If fewer than 15 slides (but not less than 10) are available during the base period, the patient may still be eligible after discussion with the medical monitor. This specimen must be accompanied by a relevant pathology report.
- Fine needle aspiration (defined as unpreserved tissue structure and used as a sample for cell suspension and/or cell smear), brushing or sedimentation of cells (for example: taken from pleural effusion and Lavage specimens) are not accepted.
- Tumor tissues taken from bone metastases after decalcification are not accepted.
- For thick needle biopsies, it is recommended that at least three thick needle specimens be embedded in a single paraffin block and sent for evaluation.
9. According to RECIST (Solid Tumor Response Evaluation Criteria) Version 1.1, it is defined as a measurable disease
- A lesion that has received radiation is regarded as a measurable disease when it has been clearly recorded that the disease has deteriorated since radiation therapy and the lesion that has received radiation is not the only disease site.
10. The following test results were obtained within 14 days before random assignment, which showed that blood and peripheral organs were adequate:
- Absolute Neutrophil Count (ANC) d 1500, no granulocyte colony stimulating factor support (without granulocyte colony stimulating factor support)
- Lymphocyte count d 500
- Platelet count d 100,000 (without blood transfusion)
- Heme d 9.0 g/dL
Patients can meet this condition by receiving blood transfusions.
- International Normalized Ratio (INR) or Partial Coagulation Time (aPTT) & T1.5 times the upper limit of normal (ULN)
This condition is only applicable to those who have not received anticoagulation therapy, and patients receiving anticoagulation therapy should maintain a stable dose.
- Aspartic acid transamination (AST), Alanine transamination (ALT) and alkaline phosphate T2.5 times the upper limit of normal , With the following exceptions:
Patients with known liver metastases: AST and/or ALT T5 times the upper limit of normal
Cases showing patients with liver or bone cancer metastasis: alkaline phosphate T5 times the upper limit of normal.
- Serum bilirubin T1.25 times the upper limit of normal
Patients with known Gilbert's disease and serum bilirubin T3 times the upper limit of normal can be included in the trial.
- Serum creatinine T 1.5 times the upper limit of normal.
11. For female patients with fertility, it should be agreed (by the patient and/or their partner) to adopt a contraceptive method that is highly effective and continues to be used in the correct way, with a very low failure rate (<1% per year). After receiving the last dose of atezolizumab, continue to use this contraceptive method for 5 months, and continue to use this method for 30 days after the last dose of nanogranular albumin paclitaxel (nab-paclitaxel), or after receiving the last dose of paclitaxel (paclitaxel). ) 6 months later, whichever is later.
For male patients with female partners who are fertile, it should be agreed (by the patient and/or their partner) to adopt a highly effective method, and when used continuously in the correct way, the failure rate is very low (every year 1%), and continue to use the last dose of nanogranular albumin paclitaxel (nab-paclitaxel), paclitaxel (paclitaxel) and/or carboplatin for 6 months. Such methods include: compound (contains estrogen and progesterone) oral contraceptives, oral contraceptives containing only progesterone to inhibit ovulation combined with another barrier method containing spermicide, intrauterine contraceptive device (IUD): intrauterine Dosage system (IUS), bilateral tubal ligation or partner vasectomy (with the knowledge that there is only one partner for the entire trial period), and abstinence. Men must avoid sperm donation during the trial period and 6 months after the last dose of nab-paclitaxel, paclitaxel and/or carboplatin, whichever is later .
12. Oral contraceptives must be combined with other contraceptive methods, because oral contraceptives may have potential interactions with test drugs. If the partner of a male patient participating in this clinical trial is fertile, the same rules apply to male patients participating in this clinical trial. Male patients must use condoms.
13. Women who have not been menopausal (non-treatment-induced amenorrhea lasting d12 months) or surgically sterilized within 14 days before starting to use the test drug must undergo a serum pregnancy test to obtain a negative result.
Exclusion Criteria
Exclude conditions
Patients who meet any of the following conditions will be excluded from this trial.
Cancer-specific exclusion
1. During the screening and previous radiological evaluation, a central nervous system metastasis that is determined to be active or untreated by computed tomography (CT) or magnetic resonance imaging (MRI) evaluation.
2. Spinal cord compression that has not been clearly treated by surgery and/or radiation, or spinal cord compression that has been diagnosed and treated before randomization, and there is no evidence that it is clinically stable for more than 2 weeks.
3. Cerebrospinal membrane disease
4. Poorly controlled tumor-related pain
- When entering the trial, patients taking analgesics must maintain a stable dose.
- Symptomatic lesions suitable for palliative radiotherapy (for example: bone metastasis, or squeezed nerve metastasis) should be treated before randomization, and patients should recover from the effects of radiotherapy. Among them, there is no required minimum recovery period.
- For asymptomatic metastatic lesions that may cause functional defects or intractable pain in growth conditions (for example: epidural metastasis without spinal cord compression), localization should be considered before random assignment when circumstances permit. treatment.
5. Poorly controlled pleural effusion, pericardial effusion or ascites that requires multiple drainage procedures (once a month or more).
- Patients who use indwelling catheters (such as long-term indwelling thoracic drainage tubes (PleurX®) can participate in the trial.
6. Poorly controlled or symptomatic hypercalcemia (calcium ion 1.5 mmol/L, calcium 12 mg/dL, or serum calcium correction value Gongshang` value upper limit).
- Patients who were using denosumab before randomization must be willing to switch to bisphosphonates during the trial and be eligible.
7. Those who have had a malignant tumor other than non-small cell lung cancer in the 5 years before random assignment, except for those with negligible risk of metastasis or death (for example: expected 5-year overall survival 90%) accept the expectation Patients who have achieved a cure (such as fully treated cervical carcinoma in situ, basal or squamous cell skin cancer, local prostate cancer undergoing curative surgery, and ductal carcinoma in situ undergoing curative surgery) are absent This limit.
8. From other clinical trials based on IHC analysis to determine the PD-L1 performance status of the tumor (for example, during the trial screening period, it has been determined that the PD-L1 performance status is accompanied by anti-PD-1 or anti-PD-L1 antibodies, but is not eligible Patients were excluded).
General medical exclusion
1. Women who are pregnant, breastfeeding, or intend to become pregnant during the trial period.
2. Had severe allergies, systemic allergies or other allergic reactions to chimeric/human-derived antibodies or fusion proteins.
3. Known to be allergic or allergic to the biopharmaceuticals produced by Chinese hamster ovary cells or any ingredients in the atezolizumab formula.
4. Have had autoimmune diseases, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid syndrome related vascular embolism, Wegener's granulomatosis (Wegener's granulomatosis), Sjogren's syndrome (Sjö gren's syndrome), Guillain-Barré syndrome, multiple sclerosis, vasculitis or glomerulonephritis.
- Patients with autoimmune hypothyroidism and receiving stable doses of thyroxine supplementation are deemed eligible for this trial.
- Patients with well-controlled type 1 diabetes who receive insulin at a stable dose are considered eligible for this trial.
- Patients suffering from eczema, psoriasis, or leukoplakia that are only manifested on the skin and chronic lichen simplex (for example: patients with psoriatic arthritis will be excluded), if they meet the following conditions, they can be included in the trial:
The body surface area (BSA) covered by the rash must be less than 10%
The disease is well controlled at the base stage, and only weak topical steroids are required
No acute deterioration of the underlying condition in the past 12 months (no need to administer PUVA [psoralen] plus UV A irradiation], per sot [methotrexate], retinoids [retinoids], biological agents , Oral calcineurin酶 [calcineurin] inhibitor, potent or oral steroid).
5. With a history of spontaneous pulmonary fibrosis, organic pneumonia (bronchiolitis obliterans), drug-induced pneumonia, spontaneous pneumonia, or evidence of acute pneumonia found on a chest computer tomography during screening
- A history of radiation pneumonitis (fibrosis) at the site of radiation therapy is permissible.
6. Human immunodeficiency virus (HIV) test result is positive
All patients will be tested for HIV before being included in the trial; patients who test positive for HIV will not be able to participate in clinical trials.
7. Active hepatitis B (chronic or acute; defined as a positive test result for hepatitis B surface antigen [HBsAg] at screening) or hepatitis C patients
- Patients who have been infected with hepatitis B virus (HBV) or have remission of HBV infection (defined as hepatitis B core antibody [HBcAb] positive and hepatitis B surface antigen [HBsAg] negative) must be HBV DNA negative , Fang can be considered eligible. Patients who are positive for hepatitis C virus (HCV) antibodies are considered eligible if they are negative for HCV RNA after PCR.
8. Active tuberculosis.
9. Serious infections occurred within 4 weeks before random assignment, including but not limited to hospitalization due to infection, bacteremia, or severe pneumonia complications.
10. Have received therapeutic oral or intravenous antibiotics within 2 weeks before random assignment.
- Patients who have received prophylactic antibiotics (for example, for the prevention of urinary tract infections or prevention of acute onset of chronic obstructive pulmonary disease) are considered eligible.
11. Major cardiovascular diseases, such as heart disease or cerebrovascular accident (level 2 or higher) as defined by the New York Heart Association, myocardial infarction, unstable arrhythmia, or unstable type occurred within 3 months before random assignment Angina.
- Known coronary artery disease, congestive heart failure (but does not meet the above conditions), or left ventricular ejection fraction 50% of patients must be stably recognized by the treating physician The best course of treatment should be referred to a cardiologist when the situation permits.
12. Randomly assign patients who have undergone major surgical procedures other than diagnosis within the previous 28 days, or are expected to undergo major surgery during the trial period.
13. Have received allogeneic bone marrow transplantation or solid organ transplantation.
14. Vaccine live attenuated vaccine within 4 weeks before random assignment, or expect to be vaccinated with live attenuated vaccine during the trial period.
15. The existence of any other diseases, abnormal metabolic function, physical examination findings, or clinical laboratory findings can reasonably suspect a certain disease or medical condition, which may make it impossible to use the test drug or may affect the interpretation of the test result , Or increase the patient’s risk of drug complications.
16. The patient’s disease or condition will affect the patient’s ability to understand, follow, and/or follow the test procedures.
Drug-related exclusions
1. Receive any approved anti-cancer therapy, including hormonal therapy, within 21 days before starting the trial treatment, except for the following conditions
- TKIs (tyrosine stimulants酶 inhibitors) approved for the treatment of non-small cell lung cancer have been discontinued for more than 7 days before random assignment. Baseline scans must be performed after stopping the previous TKIs (tyrosine stimulants inhibitors).
2. Receiving other experimental drug treatments with the intent of treatment within 28 days before random assignment.
3. Previously received CD137 agonist or immune checkpoint blocking therapy, anti-PD-1 and anti-PD-L1 therapeutic antibodies.
- Patients who have previously received anti-CTLA-4 therapy can be included, provided that they meet the following requirements:
"It has been at least 6 weeks before receiving the last dose of anti-CTLA-4 before random assignment."
After receiving anti-CTLA-4, there has been no severe immune vector adverse effects (NCI CTCAE level 3 and 4).
4. Have received systemic immunostimulants (including but not limited to interferon [IFN], interleukin-2 [IL-2] within 4 weeks before random assignment or within the five half-life period of the drug (whichever is the longer) ]).
- Previous cancer vaccines are permissible.
5. Received systemic immunosuppressive drugs (including but not limited to corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents [anti-TNF] within 2 weeks before random assignment ]) Treatment.
- Patients who have received acute, low-dose (oral prednisone �T 10 mg or equivalent), systemic immunosuppressive drugs, can participate in the trial.
- Use of corticosteroids for chronic obstructive pulmonary disease (prednisone T 10 mg or equivalent), use of mineral cortisol (for example, fludrocortisone) for postural hypotension, and lack of adrenal cortex function The use of low-dose corticosteroid supplements is permissible.
Exclusions related to chemotherapy
1. Known to have had severe allergic reactions to platinum compounds or mannitol
2. Known to be allergic to paclitaxel or any component of the nanogranular albumin paclitaxel (nab-paclitaxel).
3. According to the definition of the National Cancer Institute's Common Adverse Events Evaluation Criteria (NCI CTCAE) version 4.0, peripheral neuropathy (paclitaxel and nanogranular albumin paclitaxel ( nab-paclitaxel))
4. Known to have had severe allergic reactions to products containing Cremophor EL) (for example: Cyclosporin Concentrate for Injection and Teniposide Concentrate for Injection).
Patients who meet any of the following conditions will be excluded from this trial.
Cancer-specific exclusion
1. During the screening and previous radiological evaluation, a central nervous system metastasis that is determined to be active or untreated by computed tomography (CT) or magnetic resonance imaging (MRI) evaluation.
2. Spinal cord compression that has not been clearly treated by surgery and/or radiation, or spinal cord compression that has been diagnosed and treated before randomization, and there is no evidence that it is clinically stable for more than 2 weeks.
3. Cerebrospinal membrane disease
4. Poorly controlled tumor-related pain
- When entering the trial, patients taking analgesics must maintain a stable dose.
- Symptomatic lesions suitable for palliative radiotherapy (for example: bone metastasis, or squeezed nerve metastasis) should be treated before randomization, and patients should recover from the effects of radiotherapy. Among them, there is no required minimum recovery period.
- For asymptomatic metastatic lesions that may cause functional defects or intractable pain in growth conditions (for example: epidural metastasis without spinal cord compression), localization should be considered before random assignment when circumstances permit. treatment.
5. Poorly controlled pleural effusion, pericardial effusion or ascites that requires multiple drainage procedures (once a month or more).
- Patients who use indwelling catheters (such as long-term indwelling thoracic drainage tubes (PleurX®) can participate in the trial.
6. Poorly controlled or symptomatic hypercalcemia (calcium ion 1.5 mmol/L, calcium 12 mg/dL, or serum calcium correction value Gongshang` value upper limit).
- Patients who were using denosumab before randomization must be willing to switch to bisphosphonates during the trial and be eligible.
7. Those who have had a malignant tumor other than non-small cell lung cancer in the 5 years before random assignment, except for those with negligible risk of metastasis or death (for example: expected 5-year overall survival 90%) accept the expectation Patients who have achieved a cure (such as fully treated cervical carcinoma in situ, basal or squamous cell skin cancer, local prostate cancer undergoing curative surgery, and ductal carcinoma in situ undergoing curative surgery) are absent This limit.
8. From other clinical trials based on IHC analysis to determine the PD-L1 performance status of the tumor (for example, during the trial screening period, it has been determined that the PD-L1 performance status is accompanied by anti-PD-1 or anti-PD-L1 antibodies, but is not eligible Patients were excluded).
General medical exclusion
1. Women who are pregnant, breastfeeding, or intend to become pregnant during the trial period.
2. Had severe allergies, systemic allergies or other allergic reactions to chimeric/human-derived antibodies or fusion proteins.
3. Known to be allergic or allergic to the biopharmaceuticals produced by Chinese hamster ovary cells or any ingredients in the atezolizumab formula.
4. Have had autoimmune diseases, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid syndrome related vascular embolism, Wegener's granulomatosis (Wegener's granulomatosis), Sjogren's syndrome (Sjö gren's syndrome), Guillain-Barré syndrome, multiple sclerosis, vasculitis or glomerulonephritis.
- Patients with autoimmune hypothyroidism and receiving stable doses of thyroxine supplementation are deemed eligible for this trial.
- Patients with well-controlled type 1 diabetes who receive insulin at a stable dose are considered eligible for this trial.
- Patients suffering from eczema, psoriasis, or leukoplakia that are only manifested on the skin and chronic lichen simplex (for example: patients with psoriatic arthritis will be excluded), if they meet the following conditions, they can be included in the trial:
The body surface area (BSA) covered by the rash must be less than 10%
The disease is well controlled at the base stage, and only weak topical steroids are required
No acute deterioration of the underlying condition in the past 12 months (no need to administer PUVA [psoralen] plus UV A irradiation], per sot [methotrexate], retinoids [retinoids], biological agents , Oral calcineurin酶 [calcineurin] inhibitor, potent or oral steroid).
5. With a history of spontaneous pulmonary fibrosis, organic pneumonia (bronchiolitis obliterans), drug-induced pneumonia, spontaneous pneumonia, or evidence of acute pneumonia found on a chest computer tomography during screening
- A history of radiation pneumonitis (fibrosis) at the site of radiation therapy is permissible.
6. Human immunodeficiency virus (HIV) test result is positive
All patients will be tested for HIV before being included in the trial; patients who test positive for HIV will not be able to participate in clinical trials.
7. Active hepatitis B (chronic or acute; defined as a positive test result for hepatitis B surface antigen [HBsAg] at screening) or hepatitis C patients
- Patients who have been infected with hepatitis B virus (HBV) or have remission of HBV infection (defined as hepatitis B core antibody [HBcAb] positive and hepatitis B surface antigen [HBsAg] negative) must be HBV DNA negative , Fang can be considered eligible. Patients who are positive for hepatitis C virus (HCV) antibodies are considered eligible if they are negative for HCV RNA after PCR.
8. Active tuberculosis.
9. Serious infections occurred within 4 weeks before random assignment, including but not limited to hospitalization due to infection, bacteremia, or severe pneumonia complications.
10. Have received therapeutic oral or intravenous antibiotics within 2 weeks before random assignment.
- Patients who have received prophylactic antibiotics (for example, for the prevention of urinary tract infections or prevention of acute onset of chronic obstructive pulmonary disease) are considered eligible.
11. Major cardiovascular diseases, such as heart disease or cerebrovascular accident (level 2 or higher) as defined by the New York Heart Association, myocardial infarction, unstable arrhythmia, or unstable type occurred within 3 months before random assignment Angina.
- Known coronary artery disease, congestive heart failure (but does not meet the above conditions), or left ventricular ejection fraction 50% of patients must be stably recognized by the treating physician The best course of treatment should be referred to a cardiologist when the situation permits.
12. Randomly assign patients who have undergone major surgical procedures other than diagnosis within the previous 28 days, or are expected to undergo major surgery during the trial period.
13. Have received allogeneic bone marrow transplantation or solid organ transplantation.
14. Vaccine live attenuated vaccine within 4 weeks before random assignment, or expect to be vaccinated with live attenuated vaccine during the trial period.
15. The existence of any other diseases, abnormal metabolic function, physical examination findings, or clinical laboratory findings can reasonably suspect a certain disease or medical condition, which may make it impossible to use the test drug or may affect the interpretation of the test result , Or increase the patient’s risk of drug complications.
16. The patient’s disease or condition will affect the patient’s ability to understand, follow, and/or follow the test procedures.
Drug-related exclusions
1. Receive any approved anti-cancer therapy, including hormonal therapy, within 21 days before starting the trial treatment, except for the following conditions
- TKIs (tyrosine stimulants酶 inhibitors) approved for the treatment of non-small cell lung cancer have been discontinued for more than 7 days before random assignment. Baseline scans must be performed after stopping the previous TKIs (tyrosine stimulants inhibitors).
2. Receiving other experimental drug treatments with the intent of treatment within 28 days before random assignment.
3. Previously received CD137 agonist or immune checkpoint blocking therapy, anti-PD-1 and anti-PD-L1 therapeutic antibodies.
- Patients who have previously received anti-CTLA-4 therapy can be included, provided that they meet the following requirements:
"It has been at least 6 weeks before receiving the last dose of anti-CTLA-4 before random assignment."
After receiving anti-CTLA-4, there has been no severe immune vector adverse effects (NCI CTCAE level 3 and 4).
4. Have received systemic immunostimulants (including but not limited to interferon [IFN], interleukin-2 [IL-2] within 4 weeks before random assignment or within the five half-life period of the drug (whichever is the longer) ]).
- Previous cancer vaccines are permissible.
5. Received systemic immunosuppressive drugs (including but not limited to corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents [anti-TNF] within 2 weeks before random assignment ]) Treatment.
- Patients who have received acute, low-dose (oral prednisone �T 10 mg or equivalent), systemic immunosuppressive drugs, can participate in the trial.
- Use of corticosteroids for chronic obstructive pulmonary disease (prednisone T 10 mg or equivalent), use of mineral cortisol (for example, fludrocortisone) for postural hypotension, and lack of adrenal cortex function The use of low-dose corticosteroid supplements is permissible.
Exclusions related to chemotherapy
1. Known to have had severe allergic reactions to platinum compounds or mannitol
2. Known to be allergic to paclitaxel or any component of the nanogranular albumin paclitaxel (nab-paclitaxel).
3. According to the definition of the National Cancer Institute's Common Adverse Events Evaluation Criteria (NCI CTCAE) version 4.0, peripheral neuropathy (paclitaxel and nanogranular albumin paclitaxel ( nab-paclitaxel))
4. Known to have had severe allergic reactions to products containing Cremophor EL) (for example: Cyclosporin Concentrate for Injection and Teniposide Concentrate for Injection).
The Estimated Number of Participants
-
Taiwan
70 participants
-
Global
1200 participants
