| Eligibility |
Inclusion Criteria:
- Histologically or cytologically confirmed ES-SCLC, defined by the American Joint
Committee on Cancer (AJCC) 8th edition or the Veterans Administration Lung Study Group
(VALG) staging system.
- No prior treatment for ES-SCLC. (Patients who have received prior chemoradiotherapy
for limited-stage SCLC must have been treated with curative intent and experienced a
treatment-free interval of = 6 months between the completion of chemotherapy,
radiotherapy, or chemoradiotherapy and diagnosis of ES-SCLC).
- ECOG performance status = 1.
- Life expectancy = 3 months.
Adequate organ function as indicated by the following laboratory values (obtained = 7 days
before first dose):
- Absolute neutrophil count (ANC) = 1.5 × 109/L, platelets = 100 × 109/L,hemoglobin = 90
g/L.
- International normalized ratio (INR) or prothrombin time (PT) = 1.5 x upper limit of
normal (ULN).
- Activated partial thromboplastin time (aPTT) = 1.5 x ULN.
- Serum total bilirubin = 1.5 x ULN.
- Aspartate and alanine aminotransferase (AST and ALT) = 2.5 x ULN, or AST and ALT = 5 x
ULN for patients with liver metastases.
- Serum albumin (ALB) = 25g/L.
- Serum creatinine = 1.5 x ULN or estimated glomerular filtration rate (GFR) = 60
mL/min/1.73 m2 by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)
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.
- 18 to 75 years old on the day of signing the informed consent form (ICF).
- Fertile patients must be willing to use highly effective contraception during the
study period and for 120 days after the last dose of tislelizumab.
Exclusion Criteria:
- Active leptomeningeal disease or uncontrolled, untreated brain metastasis:
Patients with a history of treated and, at the time of screening, asymptomatic central
nervous system (CNS) metastases are eligible if they meet all the following:
- only supratentorial metastases allowed.
- No radiotherapy for the central nervous system within 14 days prior to screening.
- Received prior therapies targeting PD-1, PD-L1, CTLA-4 or other immune checkpoints.
- Received prior anti-VEGF or VEGFR TKI agents including but not limited to
Sitravatinib.
- 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 28 days prior to initiation of study treatment.
- Clinically uncontrolled pleural effusion, ascites, pericardial effusion that requires
treatment and may affect study treatment estimated by investigator.
- History of allergic reactions to any study drugs or any component of the preparation
or any component of the container.
- Patients with untreated chronic hepatitis B (HBV) or chronic HBV carriers whose HBV
DNA = 500 IU/mL (2500 copies/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, or
antiviral therapy, within 14 days prior to first dose of study drug(s). Note:
antiviral therapy is permitted for patients with viral hepatitis.
- Prior allogeneic stem cell transplantation or organ transplantation.
- 12.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, that may affect study treatment estimated by investigator.
- 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.
- 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.
- History of interstitial lung disease, noninfectious pneumonitis or uncontrolled
diseases including pulmonary fibrosis, acute lung diseases, etc, that may affect study
treatment estimated by investigator.
- Significant history or clinical manifestation of any organ systems disorder, as
determined by the investigator, that may affect study treatment estimated by
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.
- Was administered a live vaccine = 4 weeks before screening.
- A known history of HIV infection.
- Any active malignancy = 2 years before first dose of study drugs 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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