A Trial of Sintilimab Plus Anlotinib For Metastatic NSCLC After First-Line PD-1 Inhibitor

NCT04691388 | Completed Phase 2

• 1 other identifier: IRB-2020-246
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

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.

Conditions

NSCLC

Keywords

sintilimab; anlotinib; NSCLC

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate

  ORR assessed by the investigator, including proportions of complete and partial response;

  4 weeks

Secondary Outcomes (4)

• Overall Survival

  5 year

• Progression Free Survival

  2 year

• Disease Control Rate

  1 year

• Adverse events

  1 year

Study Arms (1)

sintilimab +anlotinib

EXPERIMENTAL

Drug: sintilimab combined with anlotinib

Interventions

sintilimab combined with anlotinib DRUG

All patients will receive sintilimab combined with anlotinib every 3 weeks

sintilimab +anlotinib

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;

You may not qualify if:

• 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; 6. 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;
• There is any active autoimmune disease or a history of autoimmune disease (such as the following, but not limited to: autoimmune hepatitis, interstitial pneumonia, enteritis, vasculitis, nephritis; subjects need bronchodilators for medical treatment Interventional asthma cannot be included); however, the following patients are allowed to be included in the group: vitiligo, psoriasis, alopecia, well-controlled type I diabetes that do not require systemic treatment, and hypothyroidism with normal thyroid function after replacement therapy;
• It is necessary to use immunosuppressive agents or systemic therapy to achieve the purpose of immunosuppression (dose\>10mg/day prednisone or other curative hormones), and continue to use within 2 weeks of the first administration;
• Within 4 weeks before the first administration, any patients with bleeding or bleeding event ≥ CTCAE Grade 3, or unhealed wounds, ulcers or fractures;
• Those who have previously received radiotherapy, chemotherapy, or surgery, after the completion of the treatment (last medication), less than 4 weeks from the first administration, less than 5 drug half-lives of oral targeted drugs; or less than 14 days of oral fluorouracil drugs, mitogen Those who have been less than 6 weeks of C and nitrosourea; those whose adverse events (except for hair loss) caused by previous treatment have not recovered to ≤ CTCAE 1 degree;
• Abnormal blood coagulation function (INR\>1.5 or prothrombin time (PT)\>ULN+4 seconds or APTT\>1.5 ULN), have bleeding tendency or are receiving therapeutic thrombolysis or anticoagulation therapy; Note: in prothrombin The use of anticoagulant drugs for preventive purposes is permitted provided that the international normalized ratio of time (INR) ≤ 1.5.
• Renal insufficiency: Urine routine test indicates urine protein ≥ ++, or confirmed 24-hour urine protein ≥ 1.0g;

Sponsors & Collaborators

• Zhejiang Cancer Hospital: lead
• Chia Tai Tianqing Pharmaceutical Group Co., Ltd.: collaborator
• Innovent Biologics (Suzhou) Co. Ltd.: collaborator

Study Sites (1)

Zhejiang Cancer Hospital

Hangzhou, Zhejiang, 310022, China

Location

Related Publications (1)

• Shi X, Lin C, Lou L, He Q, Lou G, Hong W, Shao L, Zhao J, Gu C, Yu X, Jin Y. An Open-Label, Single-Arm, Phase II Trial of Sintilimab Plus Anlotinib for Metastatic Non-Small Cell Lung Cancer After First-Line PD-(L)1 Inhibitor. Cancer Med. 2025 Sep;14(17):e71191. doi: 10.1002/cam4.71191.

  PMID: 40908570 DERIVED

MeSH Terms

Interventions

anlotinib

Study Officials

• Xinmin Yu, doctor

  Zhejiang Cancer Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief physician

Study Record Dates

• First Submitted: December 11, 2020
• First Posted: December 31, 2020
• Study Start: March 1, 2021
• Primary Completion: September 4, 2024
• Study Completion: December 1, 2024
• Last Updated: December 5, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)