| Eligibility |
Inclusion Criteria:
- 1 NSCLC confirmed by pathology (histology or cytology)
2. First line treatment of patients with immune combined with chemotherapy into immune
maintenance treatment;
3. 18-75 years old, both male and female;
2. There are stage IIIA, IIIB or IIIc NSCLC diagnosed according to the 8th edition of
the American Joint Committee on cancer.
3. Stage III NSCLC that cannot undergo radical surgery was confirmed and recorded by
the multidisciplinary tumor committee or the treating physician in consultation with
the thoracic surgeon.
4. In the whole body fluorodeoxyglucose (FDG) - pet or FDG-PET / CT and diagnostic
quality CT or MRI scans of the chest, abdomen, pelvis and brain, there was no evidence
of metastatic disease as stage IV NSCLC.
Note: unless otherwise demonstrated, the presence of pleural / pericardial effusion is
considered to indicate metastatic disease. For pleural effusion in both CT chest scan and
frontal chest X-ray examination, pleural puncture is required to confirm that the pleural
effusion is cytologically negative. Participants whose effusion was exudate were excluded,
even if their effusion was cytologically negative. Subjects who have met the remaining
inclusion / exclusion criteria, and pleural effusion is not visible on chest X-ray
examination in front and side views, or there is too little effusion to be safely extracted
can enter the study.
5. Having a measurable disease as defined in RECIST 1.1, at least one lesion is suitable as
a target lesion (determined by the investigator / imaging review of the local research
center).
4. No more than 28 days before the first study, CT or MRI scan, at least one previous
target lesion without radiotherapy (recistv1.1).
5. No previous treatment (chemotherapy, targeted therapy or radiotherapy) for stage III
NSCLC.
6. ECoG physical fitness status is 0 or 2 points.
7. Life expectancy is at least 12 weeks.
8. No antiangiogenic drugs or PARP inhibitors have been used in previous treatment;
9. All acute toxic reactions caused by previous anti-tumor treatment or surgery are
relieved before the screening period
Level 10.0-1 (judged according to NCI CTCAE 5.0) or to the level specified in the inclusion
/ exclusion criteria
(except for hair loss and other toxicity that the researchers believe does not pose a
safety risk to the subject).
11. No blood transfusion and blood products were used within 14 days before the first
administration, and G-CSF and other hematopoietic stimulating factors were not used for
correction.
12. Before the first drug study, the laboratory test values meet the following conditions:
1. Blood routine:
White blood cell count (WBC) = 3.0 × 109/L;
Absolute neutrophil count (ANC) = 1.5 × 109/L;
Platelet (PLT) = 100 × 109/L;
Hemoglobin content (Hgb) = 9.0 g / dl;
2. Liver function:
Aspartate aminotransferase (AST) = 2.5xuln in subjects without liver metastasis,
Alanine liver aminotransferase (ALT) = 2.5x ULN;
ALT and AST of patients with liver metastasis were < 5xuln;
Serum total bilirubin (TBIL) = 1.5xuln (excluding Gilbert syndrome, total bilirubin <
3.0mg/dl); Albumin (ALB) = 3G / dl;
3. Renal function:
Serum creatinine = 1.5xuln or creatinine clearance rate (CrCl) = 40ml / minute
4. Coagulation function:
International standardization ratio (INR) = 1.5, activated partial thromboplastin time
(APTT) = 1.5 x ULN;
5. Others:
Lipase = 1.5xuln. If lipase > 1.5xuln but there is no clinical or imaging confirmed
pancreatitis, it can be included in the group;
Amylase = 1.5xuln. If amylase > 1.5xuln but there is no clinical or imaging confirmed
pancreatitis, it can be included in the group.
Alkaline phosphatase (ALP) = 2.5uln, ALP = 5uln in subjects with bone metastasis;
13. For female subjects of childbearing age who are not sterilized surgically, the
serum hCG test must be negative and non lactating within 3 days before the first
medication. Contraceptive drugs must be used by male subjects within 6 months after
the end of the reproductive age;
14. The subjects voluntarily joined the study, with good compliance, safety and
survival follow-up.
Exclusion Criteria:
1. Suffering from small cell lung cancer or mixed tumor with small cell components.
Note: subjects with squamous NSCLC are not eligible for pemetrexed containing
chemotherapy.
2. Have a history of MDS / AML, current diagnosis or characteristics suggestive of
these diseases.
3. Weight loss > 10% (from baseline) has been recorded in the past 3 months.
4. There is a radiotherapy plan, in which the volume (V20) of the whole lung (whole
lung v20-gtv) with a total radiation dose of > 20 Gy may exceed that of the lung.
34% of the volume. Note: subjects must be evaluated by a radiation oncologist
during screening.
5. received previous chest radiotherapy, including radiotherapy for esophageal,
mediastinal or breast cancer.
6. Previous treatment with anti-PD-1, anti-PD-L1 or anti-PD-L2 drugs or drugs
targeting another stimulatory or co inhibitory T cell receptor (e.g. CTLA-4,
OX-40, CD137).
7. Previous treatment with fluzopari or any other PARP inhibitor.
8. Major surgery (other than vascular access implantation) was performed within 4
weeks before the first administration of the study drug. Note: if the subject has
had major surgery or vascular access implantation, he must have fully recovered
from therapeutic toxicity and / or complications before starting the study
intervention.
9. It is expected that any other form of antitumor treatment will be required during
the study period.
10. Have received live vaccine within 30 days before the first administration of the
test drug. Examples of live vaccines include, but are not limited to, the
following vaccines: measles, mumps, rubella, chickenpox / shingles (varicella),
yellow fever, BCG and typhoid vaccines. Since seasonal influenza vaccines for
injection are usually inactivated virus vaccines, they are allowed to be used;
But intranasal influenza vaccines (e.g., FluMist ®) It is a live attenuated
vaccine, so it is not allowed to be used.
11Strong inducers of CYP3A4 (phenobarbital, enzalutamide, phenytoin, rifampicin,
rifampicin, rifapentine, carbamazepine, nevirapine and St. John's grass) or medium
inducers (e.g. bosentan, faviren and modafinil) that cannot be stopped during the
study period are currently being received. Before starting fluzopari treatment,
pentobarbital needs a 5-week washout period, and other drugs need a 3-week washout
period.
12At present, they are receiving potent inhibitors of cytochrome P450 (CYP) 3A4 (such
as itraconazole, telithromycin, clarithromycin, protease inhibitors strengthened with
ritonavir or kirostat, indinavir, saquinavir, nefinavir, bosepovir, terapivir) or
intermediate inhibitors (such as ciprofloxacin, erythromycin, diltiazem, fluconazole,
verapamil) that cannot be stopped during the study period. The elution period required
before starting fluzopari is 2 weeks.
13 The dose of piroxicam (e.g. at least 2.5 days before or after administration of
piroxicam) and other drugs other than piroxicam (at least 2.5 days after
administration of NSD).
14 In the judgment of the investigator, resting electrocardiogram (ECG) indicates
uncontrolled and potentially reversible heart disease (e.g., unstable ischemia,
uncontrolled symptomatic arrhythmia, congestive heart failure, electrolyte disorder,
etc.), or the subject has congenital long QT syndrome.
15 Having a diagnosis of immune deficiency or being treated with chronic systemic
steroids (more than 10mg prednisone or equivalent per day) or any form of
immunosuppressive therapy within 7 days before the first administration of the study
drug.
Note: glucocorticoids are permitted for the following indications:
- eye, intranasal or topical use.
- inhalants for the management of asthma or chronic obstructive pulmonary disease.
- systemic physiological corticosteroid replacement therapy for hormone replacement
therapy, preventing vomiting, regulating symptoms suspected of immunological
etiology, or as a pretreatment of IV contrast agent allergy or chemotherapeutic
agent.
16 Active autoimmune diseases requiring systemic treatment (i.e. use of disease
regulating drugs, corticosteroids or immunosuppressants) in the past 2 years.
Alternative treatment (e.g., thyroxine, insulin or physiological corticosteroid
replacement treatment due to adrenal or pituitary insufficiency) is not
considered systemic treatment and is allowed.
17 Currently or previously participated in the study of investigational drugs, or
used investigational devices within 4 weeks before the first administration of
the study intervention. Note: subjects who have entered the follow-up period of
the experimental study can participate in this study as long as they are > 4
weeks after the last administration of previous research drugs.
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