the Efficacy and Safety of Anlotinib Combined With Almonertinib in the First-line Treatment of Patients With Brain Metastases From EGFR Mutation-positive Non-small Cell Lung Cancer

NCT04978753 | Unknown Phase 2

• 1 other identifier: GASTO 1063
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

Brief Summary

Subject population：Patients with brain metastases from EGFR mutation-positive non-small cell lung cancer who have not received systemic treatment. Experimental design: Single-center, single-arm phase II clinical trial. Purpose: Efficacy and safety of Anlotinib combined with Almonertinib in the treatment of patients with brain metastases from EGFR mutation-positive non-small cell lung cancer. treatment plan: 1). Anlotinib: 12mg/time (BSA≥1.6 m2) or 10mg/time (BSA\<1.6 m2), once a day orally, taking two weeks and stopping for one week; 2). Almonertinib: 110mg, orally once a day; primary endpoint: Intracranial progression-free survival (iPFS); secondary endpoint: Objective intracranial response rate (iORR=iCR+iPR), intracranial disease control rate (iDCR=iCR+iPR+i SD), overall progression-free survival (PFS), overall survival (OS), quality of life score.

Conditions

Non-small Cell Lung Cancer; Brain Metastases

Keywords

EGFR mutation; NSCLC; brain metastases

Outcome Measures

Primary Outcomes (1)

• iPFS

  Intracranial progression-free survival

  10-25months

Secondary Outcomes (4)

• iORR

  10-25momths

• iDCR

  10-25months

• PFS

  10-25momths

• OS

  10-40months

Study Arms (1)

treatment

EXPERIMENTAL

Anlotinib (12mg/time (BSA≥1.6 m2) or 10mg/time (BSA\<1.6 m2), once a day orally, taking two weeks and stopping for one week) combine with Almonertinib (110mg, orally once a day)

Drug: Anlotinib

Interventions

Anlotinib DRUG

1. Anlotinib: 12mg/time (BSA≥1.6 m2) or 10mg/time (BSA\<1.6 m2), once a day orally, taking two weeks and stopping for one week; 2. Almonertinib: 110mg, orally once a day;

Also known as: almonertinib

treatment

Eligibility Criteria

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

You may qualify if:

• \) 18-75 years old, ECOG PS score: 0-2 points; and there is no worsening of the disease within 2 weeks before enrollment, and the expected survival time is more than 3 months; 2) Advanced non-small cell lung cancer diagnosed by histology or cytology; 3) Baseline inspection confirms that the tumor has EGFR sensitive mutations (first-generation or second-generation sequencing, the detection can accept the following two types of tissue: archive tumor tissue; tumor tissue freshly collected during the screening period); 4) Asymptomatic or mildly symptomatic brain metastases (headache, nausea or epilepsy and other symptoms can be controlled with a fixed dose of mannitol/dexamethasone/pain relievers/antiepileptic drugs for more than 3 days); 5) MRI confirmed tumor metastasis to brain parenchyma, brain lesions ≥3; or patients with 1-2 brain lesions but not suitable for local treatment or refusal to local treatment. The brain lesions must have at least one measurable lesion with a diameter of ≥5mm; 6) Have not received systemic treatment after brain metastasis (the treatment adopted by neoadjuvant treatment is not included in the treatment plan, and the recurrence within 6 months after the end of the adjuvant treatment, the adjuvant treatment part is defined as first-line treatment, and cannot be included in this study; If the recurrence is more than 6 months, adjuvant treatment will not be included in the treatment plan); 7) The main organs are functioning normally, that is, they meet the following standards:
• The standard of routine blood examination must meet (no blood transfusion within 14 days, no use of granulocyte colony stimulating factor and other hematopoietic stimulating factors):
• HB≥90g/L;
• ANC≥1.5×109/L;
• PLT ≥80×109/L;
• The biochemical inspection shall meet the following standards:
• TBIL \<1.5 times the upper limit of normal (ULN);
• ALT and AST\<2.5 ULN; if there is liver metastasis, ALT and AST\<5 ULN;
• Cr≤1.25 ULN or creatinine clearance (CCr) ≥45ml/min (Cockcroft-Gaulat formula);
• Urine protein \<2+ (when the baseline urine protein is 2+, a 24-hour urine protein quantification should be performed, and it can only be selected when it is ≤1g);
• The international normalized ratio of blood coagulation (INR) ≤ 1.5 and APTT ≤ 1.5 ULN;
• Doppler ultrasound assessment: left ventricular ejection fraction (LVEF) ≥ lower limit of normal value (50%); 8) 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 test is negative within 7 days before study entry , And must be non-lactating patients; men should agree to patients who must use contraception during the study period and within 6 months after the end of the study period.
• \) The patients voluntarily joined the study, signed an informed consent form, and had good compliance.

You may not qualify if:

• \) Small cell lung cancer (including lung cancer mixed with small cell carcinoma and non-small cell carcinoma); 2) Brain metastases accompanied by active bleeding; 3) Those who have previously used anti-tumor angiogenesis drugs (such as bevacizumab, endurance, anlotinib, etc.) treatment failure; 4) At the beginning of the study treatment, there was an unhealed toxic reaction of grade ≥2 (NCI-CTC AE4.03) related to the previous treatment: (except for hair loss and grade 2 neuropathy caused by platinum drugs) 5) Those who have a variety of factors that affect oral medications (such as uncontrollable nausea and vomiting, inability to swallow, gastrointestinal resection, chronic diarrhea and intestinal obstruction, etc.); 6) Local radiotherapy to relieve the disease within 14 days before the first administration of the study treatment; radiotherapy or extensive radiotherapy for more than 30% of the bone marrow area within 4 weeks before the first administration (for palliative treatment of non-brain metastases such as bone metastases) Except for radiotherapy); 7) Patients with any severe and/uncontrolled diseases, including:
• Patients with unsatisfactory blood pressure control (systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg);
• Meet any of the following cardiac standards: In the resting state, the average corrected QT interval (QTcF) obtained from 3 ECG examinations is ≥470 msec (Fredericia formula is used, see Appendix 4 for details). Various clinically significant heart rhythm, conduction, and resting ECG morphological abnormalities, such as complete left bundle branch block, third-degree block, second-degree block, and PR interval ≥250 msec. Various factors that may increase the risk of QTc prolongation or the risk of arrhythmia events, such as cardiac insufficiency according to NYHA standards III to IV; heart failure; hypokalemia; congenital long QT syndrome; family history with long first-degree relatives QT syndrome or sudden death of unknown cause under 40 years of age; various combined medications that may prolong the QT interval.
• Active or uncontrolled serious infection;
• Liver diseases such as cirrhosis, decompensated liver disease, chronic active hepatitis;
• Poor diabetes control (fasting blood glucose (FBG)\> 10mmol/L);
• Urine routine shows that urine protein is ≥++, and the 24-hour urine protein quantification is confirmed to be greater than 1.0 g; 8) Long-term unhealed wounds or fractures; 9) Pulmonary hemorrhage with NCI CTC AE grade\> Grade 1 occurred within 4 weeks before enrollment; other parts of bleeding with NCI CTC AE grade\> Grade 2 occurred within 4 weeks before enrollment; hemorrhage tendency (such as active peptic ulcer) Or patients who are receiving thrombolytic or anticoagulant therapy such as warfarin, heparin or their analogues; 10) Those who have had arterial/venous thrombotic events within 12 months before enrollment, such as cerebrovascular accidents (including temporary ischemic attacks, cerebral hemorrhage, cerebral infarction), deep vein thrombosis and pulmonary embolism; 11) Clinically significant hemoptysis (more than 50ml of hemoptysis per day) occurred within 3 months before enrollment; or significant clinically significant bleeding symptoms or clear bleeding tendency, such as gastrointestinal bleeding, hemorrhagic gastric ulcer, fecal occult blood at baseline ++ and above, or suffer from vasculitis, etc.; 12) Have the following past history: interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis requiring steroid therapy, clinically active interstitial lung disease; 13) People who have a history of psychotropic drug abuse and cannot be quit or have mental disorders; 14) Respiratory syndrome (≥CTC AE grade 2 dyspnea), severe pleural fluid, ascites, and pericardial effusion; 15) A history of immunodeficiency, including HIV positive or other acquired or congenital immunodeficiency diseases, or a history of organ transplantation; active infection, such as HBV (HBV DNA copy number\> 103/ml), HCV, HIV, etc.; 16) According to the judgment of the investigator, those with concomitant diseases that seriously endanger the safety of the patient or affect the completion of the study.
• \) The patient has active ingredients or inactive excipients, chemical structure and AZD9291 (and/or anlotinib) to AZD9291 (and/or anlotinib) A history of hypersensitivity to drugs similar to / or Anlotinib or AZD9291 (and/or Anlotinib).
• \) Men or women who have fertility but have not taken effective contraceptive measures, women are pregnant or breastfeeding, or have a positive pregnancy test (urine or serum) before entering the study.
• \) Because the patient is unwilling to comply with the research procedures, restrictions and requirements, the researcher determines that the patient should not participate in the research.
• \) Allogeneic bone marrow transplantation has been performed. 21) Any serious or uncontrolled eye disease may increase the safety risk of the patient according to the judgment of the investigator; 22) In the 120 days before the collection of genetic samples, whole blood without leukocytes was transfused; 23) The patient has other coexisting malignant tumors or has been diagnosed with other malignant tumors in the last 5 years, except for basal cell carcinoma, cervical or squamous cell skin cancer in situ, and papillary thyroid carcinoma.

Sponsors & Collaborators

• Li-kun Chen: lead

Study Sites (1)

Sun Yat-Sen University Cancer Center

Guangzhou, 510000, China

RECRUITING

Related Publications (1)

• Chen J, Pan Y, Li M, Yu H, Zhang B, Yu M, Hou X, Chen L. Efficacy and safety with aumolertinib plus anlotinib for untreated EGFR-mutant NSCLC with brain metastases. NPJ Precis Oncol. 2025 Dec 1;10(1):2. doi: 10.1038/s41698-025-01191-2.

  PMID: 41326640 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Brain Neoplasms

Interventions

anlotinib; aumolertinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Likun Chen

  Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Likun Chen

CONTACT

02087343410; chenlk@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: sun yat-sen university cancer center

Study Record Dates

• First Submitted: July 20, 2021
• First Posted: July 27, 2021
• Study Start: May 1, 2021
• Primary Completion: May 30, 2022
• Study Completion: December 30, 2023
• Last Updated: July 27, 2021

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)