| Eligibility |
Inclusion Criteria:
- ECOG performance status=1.
- Life expectancy = 3 months.
- Eligible patients for this study must have locally advanced, Stage III NSCLC that is
considered unresectable. histologically- or cytologically-documented NSCLC who present
with locally advanced, unresectable (Stage III) disease (according to Version 8 of the
International Association for the Study of Lung Cancer Staging Manual in Thoracic
Oncology). Patients must not have progressed following definitive, platinum-based,
concurrent chemoradiation therapy.
- First dose of study treatment is no later than 42 days after cCRT.
- Adequate organ function as indicated by the following laboratory values (obtained = 7
days before first dose)
1. Absolute neutrophil count (ANC) = 1.5 × 10^9/L,
2. Platelets = 100 × 10^9/L,
3. Hemoglobin = 90 g/L.
4. International normalized ratio (INR) or prothrombin time (PT) = 1.5 x upper limit
of normal (ULN).
5. Activated partial thromboplastin time (aPTT) = 1.5 x ULN.
6. Serum total bilirubin = 1.5 x ULN.
7. Aspartate and alanine aminotransferase (AST and ALT) = 2.5 x ULN.
8. Serum albumin =25 g/L(2.5 g/dL).
9. Serum creatinine = 1.5 x ULN or estimated glomerular. filtration rate (GFR) >50
mL/min by Cockcroft-Gault equation.
- Able to provide written informed consent by the patient or by the patient's legally
acceptable representative and can understand and agree to comply with the requirements
of the study.
- Patients of childbearing potential must be willing to use a highly effective method of
birth control for the duration of the study, and = 120 days after the last dose of
study drugs.
Exclusion Criteria:
- Mixed small cell and non-small cell lung cancer histology.
- Received prior anti-VEGF mAb or VEGFR TKI agents and prior therapies targeting PD-1,
PD-L1, CTLA-4 or other immune checkpoints.
- Have any unresolved AE=Grade 2 from prior cCRT,radiotherapy induced hearing loss, hair
loss, peripheral sensory neuropathy and fatigue is excluded.
- Grade =2 radiation pneumonitis while receiving cCRT.
- Patients with known EGFR mutation, or ALK or ROS1 rearrangement.
- Treatment with any approved systemic anti-cancer therapy or systemic
immune-stimulatory agents (including but not limited to interferons, interleukin IL-2,
and tumor necrosis factor) within 4 weeks prior to initiation of study treatment.
- Administration of live vaccine = 4 weeks before the first dose of study treatment.
- History of allergic reactions to any study drugs.
- Patients with untreated chronic hepatitis B (HBV) or chronic HBV carriers whose HBV
DNA = 500 IU/mL, patients with active hepatitis C (HCV).
- Active autoimmune diseases that require treatment and may affect study treatment
estimated by investigator.
- Any condition that required systemic treatment with either corticosteroids (> 10 mg
daily of prednisone or equivalent) or any other immunosuppressive medication= 14 days
before first dose of study drugs that may affect study treatment estimated by
investigator.
- Severe chronic or active infections requiring systemic antibacterial, antifungal,
within 14 days prior to first dose of study drug(s).
- Prior allogeneic stem cell transplantation or organ transplantation.
- Any of the following cardiovascular risk criteria:
1. Cardiac chest pain, defined as moderate pain that limits instrumental activities
of daily living, = 28 days before first dose of study drugs.
2. Symptomatic pulmonary embolism = 28 days before first dose of study drugs.
3. Any history of acute myocardial infarction = 6 months before first dose of study
drugs.
4. Any history of heart failure meeting New York Heart Association Classification
III or IV = 6 months before first dose of study drugs.
5. Any event of ventricular arrhythmia = Grade 2 in severity = 6 months before first
dose of study drugs.
6. Any history of cerebrovascular accident = 6 months before first dose of study
drugs.
7. QTc interval (corrected by Fridericia's method) > 450 msec (for males)/ > 470
msec (for females). Note: If QTc interval is > ULN on initial ECG, a follow up
ECG will be performed to exclude result.
8. Current left ventricular ejection fraction (LVEF) < institutional LLN as assessed
by echocardiography (ECHO).
9. Any episode of syncope or seizure = 28 days before the first dose of study
drug(s).
- Inadequately controlled hypertension (defined as systolic blood pressure > 150 mmHg
and/or diastolic blood pressure > 100 mmHg).
- Bleeding or thrombotic disorders or use of anticoagulants such as warfarin or similar
agents requiring therapeutic INR monitoring within 6 months before first dose of study
drugs.
- Regardless of the severity, patients with any signs or medical history of bleeding;
within 4 weeks prior to allocation, patients with any bleeding events = CTCAE level 3,
unhealed wounds, ulcers, or fractures.
- Hemoptysis>50ml/d.
- With central cavitation or tumor shown by imaging to be located around important
vascular structures or if the investigator determines that the tumor is likely to
invade important blood vessels and may cause fatal bleeding.
- Inability to swallow capsules or disease significantly affecting gastrointestinal
function, such as malabsorption syndrome, resection of the stomach or small bowel,
bariatric surgery procedures, symptomatic inflammatory bowel disease, or partial or
complete bowel obstruction.
- Patients requiring treatment with gastric pH-modifying medications including proton
pump inhibitors and/or H2 antagonist medications. Patients may switch to use of
antacids.
- History of uncontrolled diabetes, hypertension, pulmonary fibrosis, acute lung
diseases, etc.
- Significant history or clinical manifestation of any organ systems disorder, as
determined by the investigator.
- Any major surgical procedure requiring general anesthesia=28 days before initiation of
study treatment.
- Underlying medical conditions (including laboratory abnormalities) or alcohol or drug
abuse or dependence that would be unfavorable for the administration of study drug or
affect the explanation of drug toxicity or AEs or result in insufficient or might
impair compliance with study conduct.
- Known history of HIV infection.
- Any active malignancy=2 years before first dose of study treatment except for the
specific cancer under investigation in this study and any locally recurring cancer
that has been treated curatively (e.g., resected basal or squamous cell skin cancer,
superficial bladder cancer, carcinoma in situ of the cervix or breast).
- Pregnant or breastfeeding woman.
- Concurrent participation in another clinical study unless it is an observational
(non-interventional) clinical study or during the follow-up period of an
interventional study.
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