Non-small Cell Lung CancerPhase 2NCT04978753

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

A Phase 2 study testing Anlotinib in people with Non-small Cell Lung Cancer and Brain Metastases, run by Li-kun Chen at 1 site in China.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 18 to 75 years
Conditions the study is for: Non-small Cell Lung Cancer, Brain Metastases
What is being tested?: Anlotinib
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 54 participants
Where: 1 siteChina
Study dates: 1 May 2021to 30 Dec 2023
Phase: Phase 2
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 75 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

1) 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:

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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.
9) The patients voluntarily joined the study, signed an informed consent form, and had good compliance.

Who cannot join

1) 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);

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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.
17) 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).
18) 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.
19) 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.
20) 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.

Trial locations and contacts

1 site in 1 country.

Likun Chen contact

02087343410

chenlk@sysucc.org.cn

China1 site, 1 recruiting

Sun Yat-Sen University Cancer Center
Guangzhou, 510000
Xiaowen Guo, +8615013080864, guoxw@sysucc.org.cn
Recruiting

Other trials in China

About this study

Official title: Phase II Clinical Study of 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-----a Prospective, Single-arm Exploratory Study

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
Being tested: Anlotinib
Keywords: EGFR mutation, NSCLC, brain metastases
Medical subject headings: Carcinoma, Non-Small-Cell Lung, Brain Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

AnlotinibDrug
Also called almonertinib
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;

Study groups in NCT04978753
Study group	Role	What they receive
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) Receives: Drug: Anlotinib

What is being measured

The primary outcome is the main question the study is designed to answer.

iPFS
Intracranial progression-free survival
Measured: 10-25months

Secondary outcomes (4)

iORR
Objective intracranial response rate
Measured: 10-25momths
iDCR
intracranial disease control rate
Measured: 10-25months
PFS
overall progression-free survival
Measured: 10-25momths
OS
overall survival
Measured: 10-40months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1 May 202130 Dec 2023

First posted27 Jul 2021
Study start1 May 2021
Primary completion30 May 2022 (estimated)
Study completion30 Dec 2023 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Non-small Cell Lung CancerStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 54 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04978753
Sponsor's protocol ID: GASTO 1063
Status last verified: Jul 2021
First submitted: 20 Jul 2021
Last updated: 27 Jul 2021
Results posted: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

Publications

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.
PubMed 41326640

Study at a glance

From the registry record, last updated by the sponsor on 27 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Phase II Clinical Study of 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-----a Prospective, Single-arm Exploratory Study
ClinicalTrials.gov ID: NCT04978753
Acronym / sponsor ID: GASTO 1063
Conditions: Non-small Cell Lung Cancer, Brain Metastases
Keywords: EGFR mutation, NSCLC, brain metastases
Phase: Phase 2
Study type: Interventional
Recruitment status: Unknown status
Enrolment: 54 participants (estimated)
Lead sponsor: Li-kun ChenUniversity, hospital or other
Study start: 1 May 2021 (actual)
Primary completion: 30 May 2022 (estimated)
Study completion: 30 Dec 2023 (estimated)
First posted: 27 Jul 2021 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Subject population：Patients with brain metastases from EGFR mutation-positive non-small cell lung cancer who have not received systemic treatment.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
treatment	Experimental	Drug: AnlotinibAnlotinib (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)

Who may qualify

Ages: 18 to 75 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (13 listed)

1) 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;

Key exclusion criteria (11 listed)

1) 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;

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
AnlotinibAlso: almonertinib1. 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;	Drug	treatment

Primary outcome

iPFS
Time frame: 10-25months
Intracranial progression-free survival

4 secondary outcomes

iORR
Time frame: 10-25momths
iDCR
Time frame: 10-25months
PFS
Time frame: 10-25momths
OS
Time frame: 10-40months

Results and safety

Results are not available in the source record.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 27 Jul 2021.
Derived from this study: PubMed 41326640Chen 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.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Likun Chen contact

02087343410

chenlk@sysucc.org.cn

Likun Chen principal investigator

Sun Yat-sen University

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Anlotinib in people with Non-small Cell Lung Cancer and Brain Metastases, run by Li-kun Chen at 1 site in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 27 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Likun Chen (02087343410, chenlk@sysucc.org.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

iPFS (time frame: 10-25months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04978753, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jul 2021.