Lung Cancer
Conditions
Interventions
Treatment arm:anlotinib combined with sintilimab
Sponsors
Peking University Shenzhen Hospital
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Male or female patient aged >= 18 years old; 2. Patients with histological or cytological confirmed recurrent or metastatic non-small cell lung cancer; 3. Harboring KRAS mutation; 4. Previously received at least one standard systemic treatment for recurrent or metastatic diseases and treatment failed. The definition of treatment failure are: (1) Disease progression during treatment or disease progression within 3 months after the last treatment (6 months after the last neoadjuvant or adjuvant therapy), with clear evidence of imaging or clinical progression; (2) Inability to tolerate previous treatment due to adverse events. No limit for the numbers of previous treatment; 5. The interval to the last systemic treatment is >= 4 weeks and the clinically significant treatment-related toxicity has improved to grade 0 to 1 (CTCAE 5.0) at the baseline examination. 6. Patients with asymptomatic central nervous system (CNS) metastasis or asymptomatic and stable brain metastasis after treatment confirmed by computed tomography (CT) or magnetic resonance imaging (MRI) for at least 3 months, and have not treated with steroid treatment for at least 4 weeks. 7. Patients have at least one target lesion with a measurable diameter according to the RECIST 1.1 standard (CT scan with a long diameter of >= 10 mm for the tumors, or CT scan with a short diameter of >= 15 mm for lymph nodes, and the lesions have not received radiotherapy, cryosurgery and other local treatment; 8. ECOG physical status score 0~2 points (see Annex 2); 9. The baseline blood routine and biochemical indexes of the subjects meet the following criteria: (1) Hemoglobin >= 80 g/L (no blood transfusion within 14 days); Neutrophil count >= 1.5 x 10^9/L; Platelet count >= 90 x 10^9/L; (2) Serum total bilirubin = 30g/L; 10. The life expectancy is >= 3 months; 11. Women of childbearing age must undergo a pregnancy test (serum or urine) within 7 days before enrollment, and the results are negative and are willing to use appropriate methods of contraception during the trial period and 8 weeks after the last administration of the trial drug. For men, it should be surgical sterilization, or agree to use appropriate methods of contraception during the trial period and 8 weeks after the last administration of the trial drug; 12. The subjects voluntarily join the study, sign the informed consent form, have good compliance and cooperate with the follow-up.
Exclusion criteria
Exclusion criteria: Subjects with any of the following criteria cannot be enrolled: 1. Patients with any other malignancies within five years of enrollment except for cured cervical carcinoma in situ and skin basal cell carcinoma; 2. Toxicities of previous treatments failed to recover to grade = grade II myocardial ischemia or myocardial infarction, poorly controlled arrhythmias (including QTc interval >= 450ms in males, >= 470ms in females); grade III ~ IV heart failure according to NYHA criteria, or left ventricular ejection fraction (LVEF) 1.5 or PT > 4 seconds or APTT > 1.5 x ULN], have bleeding tendency or are under thrombolysis or anticoagulation therapy; 8. Daily hemoptysis >= two teaspoons before enrollment; 9. Significant clinical bleeding symptoms or definite bleeding tendency within 3 months before enrollment, such as gastrointestinal bleeding, hemorrhagic hemorrhoids, hemorrhagic gastric ulcer, fecal occult blood >= + +, or vasculitis; 10. Arteriovenous thrombosis within 12 months before enrollment, such as cerebrovascular accidents (including temporary ischemic attack, cerebral hemorrhage, cerebral infarction), deep venous thrombosis and pulmonary embolism, etc; 11. Hereditary or acquired bleeding and thrombotic tendencies (such as hemophilia, coagulation dysfunction, thrombocytopenia, hypersplenism, etc.); 12. Long-term uncured wounds or fractures (excluding pathological fractures caused by tumors); 13. Patients received major surgery or severe traumatic injury, fracture or ulcer within 4 weeks before enrollment; 14. Patients having obvious factors affecting oral drug absorption, such as inability to swallow, chronic diarrhea and intestinal obstruction; 15. Abdominal fistula, gastrointestinal perforation or abdominal abscess occurred within 6 months before enrollment; 16. Urinary protein >= + +, or 24-hour urinary protein >= 1.0 g; 17. Symptomatic serous effusion (including pleural effusion, ascites, pericardial effusion); Note: Asymptomatic serous effusion can be included; symptomatic effusion can be treated actively (anticancer drugs can not be used for serous effusion treatment), and patients are allowed to be included after being judged by the investigators; 18. Patients with active, or historical autoimmune diseases that may recur (e.g. systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, autoimmune thyroid disease, multiple sclerosis, vasculitis, glomerulonephritis, etc.), or patients at high risk of autoimmune diseases (such as immunosuppressive therapy for organ transplants); 19. Patients who are expected to have major surgery during the study including 28-day screening period; 20. Patients who need to receive systemic corticosteroids (dose equivalent to prednisone > 10 mg / day) or other immunosuppressive drugs within 14 days before the first administration of study treatment or during the study; the following circums
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| PFS; | — |
Secondary
| Measure | Time frame |
|---|---|
| ORR;DCR;OS;AE; | — |
Countries
China
Contacts
Public ContactFen Wang
Peking University Shenzhen Hospital
Outcome results
None listed