An Open-Label, Single-Arm, Phase II Trial of Sintilimab Combined With Anlotinib For Metastatic Non-Small Cell Lung Cancer After First-Line PD-1 Inhibitor
Overview
- Phase
- Phase 2
- Intervention
- sintilimab combined with anlotinib
- Conditions
- NSCLC
- Sponsor
- Zhejiang Cancer Hospital
- Enrollment
- 29
- Locations
- 1
- Primary Endpoint
- Overall Response Rate
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
The combination of immunocheckpoint inhibitors and anti-angiogenesis therapy has synergistic anti-tumor effect and is a reasonable method to improve the prognosis of patients. Therefore, in this study, it is hoped that sintilimab combined with anlotinib can overcome immunotherapy resistance, improve the efficacy of immunotherapy, and further improve the survival of patients, so as to provide more clinical evidence for the treatment of advanced NSCLC patients with negative driver gene after first-line treatment with anti-PD-1 antibody.
Detailed Description
Most cancer cells that do not respond to a single immune checkpoint inhibitor escape through the innate immune escape mechanism, allowing them to grow and survive. Different from the inherent resistance mechanism, some patients who initially responded to immune checkpoint inhibitors developed disease progression after a period of treatment and follow-up, suggesting acquired resistance. Therefore, clinical strategies continue to be applied to overcome inherent and acquired resistance to improve the clinical efficacy of immune checkpoint inhibitors. Combining an immune checkpoint inhibitor with another drug that has both immune regulation and anti-tumor properties can enhance the anti-tumor efficacy of any one drug when used alone. Studies have shown that tumor angiogenesis participates in anti-tumor immune regulation and will aggravate the tumor immunosuppressive microenvironment, and anti-angiogenesis therapy can normalize the abnormal vascular structure and function of tumors, and help the recruitment and infiltration of effector T cells. , Reduce the accumulation of immunosuppressive regulatory T cells, relieve the immunosuppressive state, thereby improving the efficacy of immunotherapy. The combination of anti-angiogenic drugs and immune checkpoint inhibitors has become a promising treatment strategy.
Investigators
Yu Xinmin
Chief physician
Zhejiang Cancer Hospital
Eligibility Criteria
Inclusion Criteria
- •The patient voluntarily participated in this study and signed an informed consent form;
- •Gender is not limited, 18-75 years old; ECOG PS score: 0\~1; The expected survival time is more than 3 months;
- •It is diagnosed as advanced (stage IV) non-small cell lung cancer by cytology or histology, and the disease has progressed after receiving PD-1 antibody treatment in the past. According to RECIST 1.1, the efficacy evaluation standard for solid tumors, it has measurable lesions;
- •Provide detectable specimens (tissue or cancerous pleural effusion) for genotype testing before enrollment, and patients whose EGFR, ALK and ROS1 gene test results are all negative;
- •The main organ functions meet the following criteria within 7 days before treatment:
- •a) Blood routine examination standard (under no blood transfusion within 14 days):
- •Hemoglobin (HB) ≥9g/dL; ② The absolute value of neutrophils (ANC) ≥ 1.5×109/L;
- •③ Platelet (PLT) ≥80×109/L b) The biochemical inspection shall meet the following standards:
- •Serum total bilirubin (TBIL) ≤ 1.5 × ULN (for patients with Gilbert syndrome, ≤ 3 × ULN); ② Alanine aminotransferase (ALT) and aspartate aminotransferase AST≤2.5ULN, such as liver metastasis, ALT and AST≤5ULN; ③ Serum creatinine (Cr)≤1.5ULN or creatinine clearance rate (CCr)≥50ml/min; c) Doppler ultrasound evaluation: left ventricular ejection fraction (LVEF) ≥ lower limit of normal (50%) d) Coagulation function: activated partial thromboplastin time (APTT), international normalized ratio (INR), prothrombin time (PT)≤1.5×ULN;
- •Women of childbearing age should agree to use contraceptive measures (such as intrauterine devices, contraceptives or condoms) during the study period and within 6 months after the end of the study; serum or urine pregnancy tests are negative within 7 days before study entry, And must be a non-lactating patient; men should agree to use contraceptive measures during the study period and within 6 months after the end of the study period;
Exclusion Criteria
- •Small cell lung cancer (including mixed small cell lung cancer and non-small cell lung cancer);
- •Previously received Anlotinib hydrochloride treatment and other immunotherapy: including but not limited to anti-CTLA-4 antibody, anti-OX40 antibody and anti-CD137 antibody treatment and other immunotherapy;
- •Those who have previously received sunitinib, sorafenib, famitinib, apatinib, regorafenib and other similar VEGFR-TKI small molecule drugs;
- •Imaging (CT or MRI) shows that the tumor focus is ≤ 5 mm from the large blood vessels, or there is a central type tumor that invades the local large blood vessels; or there is obvious lung cavity or necrotic tumor;
- •Untolerable toxicity in previous anti-PD-1/PD-L1 treatments is defined as follows:
- •≥Level 3 AE related to anti-PD-1/PD-L1; 2) ≥Level 2 immune-related AEs related to anti-PD-1/PD-L1, but AEs that have been relieved or well-controlled after suspension of anti-PD-1/PD-L1 or steroid therapy are not excluded. Past colitis, encephalitis, myocarditis, hepatitis, uveitis and non-infectious pneumonia are excluded; 3) Any level of CNS or eye AE related to anti-PD-1/PD-L1; Note: Patients with previous endocrine AEs can be admitted to the group if they can be stable and asymptomatic under appropriate replacement therapy.
- •Severe hypersensitivity after administration of other monoclonal antibodies;
- •Medical history and comorbidities
- •Patients with active and symptomatic brain metastases, cancerous meningitis, spinal cord compression, or brain or pia mater diseases found in imaging CT or MRI during screening (brain with stable symptoms and treatment completed 28 days before enrollment) Patients with metastases can be included in the group, but they need to be evaluated by MRI, CT or venography to confirm that they have no symptoms of cerebral hemorrhage);
- •Patients with a history of malignant tumors, basal cell carcinoma of the skin, superficial bladder cancer, squamous cell carcinoma of the skin, or cervical cancer in situ that have undergone possible curative treatment and have not recurred within 5 years after the start of treatment are excluded;
Arms & Interventions
sintilimab +anlotinib
Intervention: sintilimab combined with anlotinib
Outcomes
Primary Outcomes
Overall Response Rate
Time Frame: 4 weeks
ORR assessed by the investigator, including proportions of complete and partial response;
Secondary Outcomes
- Overall Survival(5 year)
- Progression Free Survival(2 year)
- Disease Control Rate(1 year)
- Adverse events(1 year)