Overview

To evaluate the efficacy and safety of almonertinib plus anlotinib as first-line treatment for advanced non-small cell lung cancer with EGFR sensitive mutation and TP53 mutation.

This study is an exploratory single-arm study. The specific treatment regimen is as follows: Non-squamous NSCLC: almonertinib (110 mg/d) plus anlotinib (12mg/d) is started on the first day of each treatment cycle and administered every three weeks until disease progression or intolerable toxicity. Anlotinib was given for two weeks, followed by one week off.

Patients are assessed for measurable disease at baseline, 6 weeks, 12 weeks after starting treatment, and every 9 weeks thereafter according to RECIST 1.1 criteria during the treatment period until disease progression or intolerable toxicity withdrawal. Following discontinuation of treatment, subjects are followed for survival status every 3 months until death. Subject safety was assessed during treatment according to NCI CTCAE Version 4.0 criteria. Subjects who experience an AE should be followed until the AE returns to baseline. The primary endpoints is Progression-free survival (PFS) . Secondary endpoints include objective response rate (ORR), overall survival (OS) and safety (NCI CTCAE v 4.0).

Statistical methods: The PFS curve was estimated using the Kaplan-Meier method for the largest population to be analyzed. The confidence interval method was used as the criterion for the main analysis. OS was calculated in the same way as the secondary endpoint. Descriptive statistics will be used to analyze ORR, DCR, etc. It is expected that almonertinib plus anlotinib as first-line treatment will prolong median PFS and OS of advanced non-small cell lung cancer with EGFR sensitive mutation and TP53 mutation patients.

Eligibility

Inclusion Criteria:

        Metastatic Non-squamous NSCLC is histologically or cytologically proven to be inoperable
        and cannot receive radical concurrent chemoradiotherapy. The conventional TNM stage was
        identified as stage IIIa-Ⅳb according to the International Association for the Study of
        Lung Cancer and the American Joint Committee on the Classification of Cancer 8th edition
        TNM Staging of Lung Cancer.
        Patients with EGFR mutation and TP53 mutation advanced Non-squamous NSCLC. Patients who had
        not previously received systemic radiotherapy and chemotherapy or who had relapsed for more
        than 6 months of follow-up after onset of adjuvant chemotherapy.
        At least one measurable lesion as determined by RECIST criteria. Male or female patients,
        age: 18-75 years of age. Performance score 0-1 based on Eastern Cooperative Oncology Group
        (ECOG) test. Expected survival period ≥12 weeks. Serum absolute number of neutrophils≥ 1.5
        x 10^9/L, platelet ≥ 100 x10^9/L, and hemoglobin≥ 90g/L.
        Serum bilirubin≤1.5 times ULNL, aspartate aminotransferase (AST) and adenosine
        triphosphate(ALT) ≤ 2.5 times ULN, alkaline phosphatase ≤ 5 times ULN.
        Serum creatinine≤ the ULN or creatinine clearance ≥ 60 mL/min. Patients who had previously
        undergone surgery have recovered for more than 4 weeks from the beginning of the project.
        Women with an intact uterus must have a negative pregnancy test within 28 days prior to
        enrolement in the study (unless it was 24 months after amenorrhea). If the pregnancy test
        is more than 7 days prior to initial dosing, a urine pregnancy test is required for
        verification (within 7 days prior to initial dosing).
        If there is a risk of conception, all patients (whether male or female) are required to use
        contraceptive measures with an annual failure rate of less than 1% throughout the treatment
        period until 120 days after the last dose of the study drug.
        Sign the inform consent form with good compliance.
        Exclusion Criteria:
        Those who are known to be allergic to the study drug almonertinib and anlotinib and its any
        components.
        Intolerance to study drug treatment or allergy to the active ingredients or excipients of
        combined chemotherapy drugs.
        Pregnancy or breastfeeding women or women who may be pregnant but are unwilling to take
        appropriate contraception.
        Existing severe acute infections that are not under control; Or suppurative and chronic
        infections with delayed healing.
        Pre-existing serious heart disease, including: congestive heart failure, uncontrolled
        high-risk arrhythmias, unstable angina pectoris, myocardial infarction, severe valvular
        heart disease, and refractory hypertension.
        People suffering from uncontrollable neuropsychiatric diseases or mental disorders had poor
        compliance and were unable to cooperate and describe treatment responses; The conditions of
        patients with primary brain tumor or central nerve metastatic tumor were uncontrollable and
        the symptoms of cranial hypertension or neuropsychiatric were obvious.
        Patients with hereditary bleeding tendency or coagulation dysfunction, or history of
        thrombosis or bleeding, and abnormal detection results of coagulation function related
        indicators.
        Patients who are receiving thrombolytic or anticoagulant therapy due to high risk of
        thrombosis.
        Patients with unhealed wounds, unhealed ulcers or unhealed fractures. Other conditions that
        the investigator considers to be inappropriate for the patient to participate in this
        trial.
        Currently participating in interventional clinical research treatment, or have received
        other investigational drugs or used investigational device treatment within 4 weeks before
        the first dose.
        Patients who have undergone major surgery within 4 weeks before the start of study
        treatment or are scheduled to undergo major surgery during the study period (except for
        surgery such as puncture or lymph node biopsy).
        Pulmonary interstitial fibrosis with respiratory failure. Chronic obstructive pulmonary
        disease with respiratory failure. Active pulmonary tuberculosis; Active autoimmune disease
        requiring systemic therapy (such as the use of disease-modifying drugs, glucocorticoids, or
        immunosuppressants) within 2 years prior to the first dose. Replacement therapy (such as
        thyroxine) is not considered systemic therapy; Those who are receiving systemic
        glucocorticoid therapy (excluding nasal spray, inhalation or other local glucocorticoids)
        or any other form of immunosuppressive therapy within 14 days before the first dose of the
        study.