A Clinical Study of the Combination of Anlotinib and Aumolertinib in the First-line Treatment of Advanced NSCLC With EGFR 21L858R Mutation

Study Overview
=================
Brief Summary
-----------------
This study is a prospective, multicenter, single arm clinical study. Thirty subjects who will have been diagnosed with locally advanced or metastatic non-small cell lung cancer with EGFR 21L858R mutation detected in lung cancer tissue or peripheral blood will be recruited and treated with anlotinib and aumolertinib. The efficacy will be evaluated according to the Solid Tumor Efficacy Evaluation Standard (RECIST 1.1), and evaluated every 6 to 8 weeks. The survival status and adverse reactions of the subjects will be recorded. The study will be terminated when the subjects experience disease progression or intolerable drug toxicity, or the subjects withdraw their informed consent. The main purpose of the study is to observe the efficacy and safety of the combined treatment regimen in such subjects. The primary endpoint of the study is median progression free survival (mPFS); The secondary study endpoints are objective response rate (ORR), disease control rate (DCR), median overall survival time (mOS), and safety.

Official Title
-----------------
A Prospective, Multicenter, Single-arm Clinical Study of the Combination of Anlotinib and Aumolertinib in the First-line Treatment of Advanced Non-small Cell Lung Cancer With EGFR 21L858R Mutation

Conditions
-----------------
Non-Small Cell Lung Cancer With Mutation in Epidermal Growth Factor Receptor

Intervention / Treatment
-----------------
* Drug: Combined therapy of anlotinib and aumolertinib


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 1) The patient voluntarily participated in this study and signed an informed consent form; 2) Age>18 years old, both male and female; 3) Advanced stage unresectable or metastatic NSCLC (stage IIIB, IIIC, or IV) confirmed by histology or cytology, with the presence of EGFR 21 exon L858R mutation in the driving gene; 4) According to the criteria for evaluating the efficacy of solid tumors (RECIST 1.1), at least one measurable lesion is used as the target lesion; 5) The Eastern Cancer Collaborative Group's Physical State Score (ECOG PS) is 0 to 3 points; 6) Expected survival time is more than 3 months; 7) Newly treated patients who have not received systematic anti-tumor treatment in the past, including radiotherapy and chemotherapy, targeted and immunotherapy; 8) The main organ function meets the following standards within 7 days before treatment:(1) Blood routine examination standard (without blood transfusion within 14 days): ① Hemoglobin (HB) ≥ 90g/L; ② Absolute value of neutrophils (ANC) ≥ 1.5 × 109/L; ③ Platelet (PLT) ≥ 80 × 109/L.(2) Biochemical examination should meet the following standards: ① Total bilirubin (TBIL) ≤ 1.5 times the upper limit of normal value (ULN); ② Alanine aminotransferase (ALT) and aspartate aminotransferase AST ≤ 2.5ULN, if accompanied by liver metastasis, ALT and AST ≤ 5ULN; ③ Serum creatinine (Cr) ≤ 1.5ULN or creatinine clearance rate (CCr) ≥ 60ml/min. Exclusion Criteria: Mixed NSCLC containing other pathological components; Poor blood pressure control (systolic blood pressure ≥ 150mmHg, diastolic blood pressure ≥ 100mmHg); Imaging shows that the tumor invades important blood vessels, or the researcher determines that the tumor is highly likely to invade important blood vessels and cause fatal massive bleeding during subsequent studies; Have experienced arteriovenous thrombosis events within 6 months, such as cerebrovascular accidents, deep venous thrombosis, and pulmonary embolism in patients; Patients with combined factors that affect oral medication, such as difficulty swallowing, gastrointestinal resection, chronic diarrhea, or intestinal obstruction; Patients with symptomatic brain metastases; Patients with severe and/or uncontrollable diseases, such as myocardial infarction, unstable angina, congestive heart failure, and severe uncontrollable arrhythmias within 6 months prior to enrollment; Active or uncontrolled severe infections; Severe liver dysfunction, cirrhosis, acute or chronic active hepatitis; The urine routine results showed that the urine protein level was ≥++, and the 24-hour urine protein quantitative detection result was>1.0g; Active pulmonary tuberculosis; Pregnant or lactating women; According to the judgement of the researchers, the subjects may have other factors that may cause the study to be terminated midway, such as other serious illnesses (including mental illness) requiring concurrent treatment, serious laboratory test abnormalities, and accompanying family and social factors, which may affect the safety of the subjects or the collection of data and samples.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental group<br>Participants who met the study protocol were treated with anlotinib and aumolertinib.Aumolertinib mesylate tablets are administered 110 mg orally once a day until disease progression or unacceptable toxicity. Anlotinib hydrochloride capsules were given 12 mg once a day, taken for 2 weeks and then discontinued for 1 week, with a treatment cycle every 21 days. If grade 3 or above treatment-related toxicity occurs, anlotinib can be reduced to 10 mg or 8 mg once daily until disease progression or unacceptable toxicity occurs. | Drug: Combined therapy of anlotinib and aumolertinib<br>* Participants were treated with anlotinib and aumolertinib.Aumolertinib mesylate tablets are administered 110 mg orally once a day,and anlotinib hydrochloride capsules were given 12 mg once a day, taken for 2 weeks and then discontinued for 1 week, with a treatment cycle every 21 days. If grade 3 or above treatment-related toxicity occurs, anlotinib can be reduced to 10 mg or 8 mg once daily.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| median Progressive Free Survival (mPFS) | The time from the subject's initiation of treatment with anlotinib and aumolertinib to the occurrence of disease progression. | up to two years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| objective response rate(ORR) | The percentage of subjects who achieved complete remission or partial remission after 6 to 8 weeks of treatment with anlotinib and aumolertinib. | 6 to 8 weeks after the subjects used the investigational drugs | 
| Disease control rate (DCR) | The percentage of subjects whose tumors shrink or remain stable after 6 to 8 weeks of treatment with anlotinib and aumolertinib. | 6 to 8 weeks after the subjects used the investigational drugs | 
| median Overall survival(mOS) | Median time from subjects' enrollment to death for any reasons. For subjects who are lost to follow-up before death, the last follow-up time will be calculated as the time of death. | up to three years | 
| Safety of combined therapy | Number of participants who had drug-related adverse reactions during the trial and the degree of adverse reactions. | up to two years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
non-small cell lung cancer;anlotinib;aumolertinib;combined therapy;efficacy