Almonertinib as First-line Treatment in Patients With EGFR Mutations Positive in Advanced NSCLC With Brain Metastases

NCT04808752 | Active Not Recruiting Phase 2

• 1 other identifier: YX-L-202107
• Study Type: interventional
• Target: 63
• Locations: 1 country
• Sites: 1

Brief Summary

This is a prospective, open-label, multi-center, single-arm clinical trial

Conditions

Lung Cancer

Keywords

almonertinib

Outcome Measures

Primary Outcomes (1)

• PFS

  The PFS time is defined as time from enrollment to locoregional or systemic recurrence, second malignancy or death due to any cause; censored observations will be the last date of : "death", "last tumor assessment", "last follow up date" or "last date in drug log"

  26 months

Secondary Outcomes (9)

• iPFS

  26 months

• iORR

  26 months

• iDoR

  26 months

• iDCR

  26 months

• ORR

  26 months

Other Outcomes (1)

• Explore gene mapping before and after the treatment.

  26 months

Study Arms (1)

Almonertinib high-dose group

EXPERIMENTAL

Patients who meet the criteria for inclusion and exclusion will be included in the high-dose almonertinib treatment group and receive oral almonertinib 165 mg once a day

Drug: Almonertinib

Interventions

Almonertinib DRUG

Patients meeting the criteria for inclusion and exclusion were included in the high-dose almonertinib treatment group and received oral almonertinib 165 mg once a day.

Also known as: Investigational Product

Almonertinib high-dose group

Eligibility Criteria

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

You may qualify if:

• Age from 18 to 75 years old.
• Histology or cytology is confirmed to be NSCLC, imaging confirmed to be advanced NSCLC with brain metastasis (including relapsed or newly diagnosed advanced patients after previous surgical treatment; according to AJCC eighth edition lung cancer staging standards).
• Tumor tissue samples or blood samples are confirmed to be EGFR sensitive mutations (including exon 19 deletion or L858R, both alone or coexist with other EGFR mutations). Tumor tissue is the first choice for examination; if the tumor tissue is not accessible or the patient cannot accept a tissue biopsy, a blood sample can be sent.
• Have not received any systemic treatment. For patients who have received local treatment, the lesion within the scope of the local treatment cannot be used as the target lesion unless the lesion has progressed.
• Patients are required to have a measurable extracranial lesion that has not undergone local treatment or has shown progression after local therapy, with a baseline longest diameter of at least 10 mm (or 15 mm for lymph nodes), and at least one intracranial lesion with a baseline longest diameter of at least 5 mm.
• The brain condition is stable for at least 2 weeks before the study drug treatment, without any systemic (oral or parenteral) corticosteroid or anticonvulsant drug treatment. Non-absorbable corticosteroids can be used locally and inhaled according to the indications.
• The Eastern Cooperative Oncology Group (ECOG) physical status score is 0 or 1, and has not deteriorated at least 2 weeks before the study drug treatment, and the expected survival period is not less than 12 weeks.
• Female patients of childbearing age are willing to take appropriate contraceptive measures and should not breastfeed from signing the informed consent to 6 months after the last study drug treatment; male patients are willing to take appropriate contraceptive measures from signing the informed consent to 6 months after the last study drug treatment Use barrier contraception (ie condoms).
• Female patients of childbearing age must have a negative serum or urine HCG test within 7 days before enrollment in the study, and they must be non-lactating.
• The subject voluntarily participated and signed an informed consent form in writing.

You may not qualify if:

• Treatment with any of the following:
• Previously received EGFR tyrosine kinase inhibitor (EGFR-TKI) treatment (such as erlotinib, gefitinib, icotinib, afatinib, osimertinib, and almonertinib, etc.) );
• Within 4 weeks before the first administration of the study drug, the patient has undergone major surgery (such as craniotomy, thoracotomy, or laparotomy, etc.), or underwent minor traumatic surgery (biopsy, bronchoscopy, and Thoracic drainage). The definition of major surgery refers to the level 3 and level 4 surgery specified in the "Administrative Measures for the Clinical Application of Medical Technology" in Appendix H, which was implemented on November 1, 2018;
• Except for patients who have received local radiotherapy (palliative bone radiotherapy for non-target lesions) within 2 weeks before the first administration of the study drug; within 4 weeks before the first administration of the study drug, more than 30% of the bone marrow has been irradiated (calculated area of the bone marrow) See Annex I), or received extensive radiotherapy; received whole brain radiotherapy due to this disease before enrollment;
• Recurrence within 6 months after adjuvant or neoadjuvant treatment for early lung cancer; if there is both neoadjuvant therapy and adjuvant therapy, the adjuvant treatment time will be calculated;
• Within 14 days before the first administration of the research drug, Chinese medicines and preparations with anti-tumor therapy or anti-tumor adjuvant therapy have been used (see Appendix E for the list of drugs);
• There is pleural effusion/peritoneal effusion that requires clinical intervention (patients who do not need to drain the effusion or who are stable for 2 weeks or more can be included in the group); there is pericardial effusion (a small amount of pericardium that is stable for 2 weeks or more) Fluid effusion is allowed to enter the group). If anti-tumor drugs have been used locally (such as chest cavity perfusion) during drainage, at least 5 drug half-lives or 21 days (whichever is shorter) must be eluted before the first administration of the study treatment before they can be included in the group;
• Within 7 days before the first administration of the study drug, have used CYP3A4 strong inhibitors, strong inducers, or narrow therapeutic window drugs with sensitive substrates, or need to continue to receive these drugs during the study period (see Appendix E for the list of drugs);
• Are receiving drugs that are known to prolong the QT interval or may cause torsades de pointes, or need to continue to receive these drugs during the study period (see Appendix E for the drug list and washout time);
• The 5 half-lives of the study drug that participates in other clinical trials as a subject or is still in other clinical trials within 4 weeks before the first administration of the study drug, whichever is longer (except for screening failure).
• Mixed SCLC and mixed NSCLC, large cell neuroendocrine carcinoma and sarcomatoid carcinoma confirmed by histology or cytology.
• At the beginning of the study drug treatment, those with unresolved residual toxicity from previous anti-tumor therapy greater than CTCAE level 1, except for hair loss and level 2 neurotoxicity caused by previous anti-tumor. In the past, intracranial hemorrhage unrelated to the tumor occurred.
• History of other primary malignant tumors, except for the following:
• Malignant tumors that have been cured, have no activity for ≥5 years and have a very low risk of recurrence before being selected for the study;
• Non-melanoma skin cancer or malignant freckle-like nevus that has been adequately treated and has no evidence of disease recurrence;

Sponsors & Collaborators

• Zhejiang Cancer Hospital: lead
• Jiangsu Hansoh Pharmaceutical Co., Ltd.: collaborator

Study Sites (1)

Cancer Hospital Affiliated to University of Chinese Academy of Sciences

Hangzhou, Zhejiang, 310000, China

Location

Related Publications (1)

• Li H, Chen K, Gong L, Qin J, Jin Y, Zhou R, Huang Z, Xu Y, Xu X, He J, Zhu J, Yu S, Lu H, Xu Y, Yu X, Han G, Chen J, Tan W, Lou G, Ren B, Chen X, Zhang D, Wang W, Shi X, Xie F, Zhao J, Han N, Li B, Fan Y. High-Dose Aumolertinib for Untreated EGFR-Variant Non-Small Cell Lung Cancer With Brain Metastases: The ACHIEVE Phase 2 Nonrandomized Clinical Trial. JAMA Oncol. 2025 Aug 1;11(8):900-908. doi: 10.1001/jamaoncol.2025.1779.

  PMID: 40569623 DERIVED

MeSH Terms

Conditions

Lung Neoplasms

Interventions

aumolertinib

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Qin Li Lu

  Zhejiang Provincial People's Hospital，Hangzhou, China

  PRINCIPAL INVESTIGATOR

• Jun Chen

  Ningbo Yinzhou People's Hospital，Ningbo, China

  PRINCIPAL INVESTIGATOR

• Ping Yu Li

  The First Affiliated Hospital of Wenzhou Medical University，Wenzhou，China

  PRINCIPAL INVESTIGATOR

• Fei J Zhu

  Taizhou Central Hospital，Taizhou，China

  PRINCIPAL INVESTIGATOR

• Bin Wang

  Huzhou Central Hospital，Taizhou，China

  PRINCIPAL INVESTIGATOR

• Wu G Wu

  Meizhou People's Hospital，Meizhou，China

  PRINCIPAL INVESTIGATOR

• Rong R Zhou

  Xiangya Hospital of Central South University，Changsha，China

  PRINCIPAL INVESTIGATOR

• Yan X Lin

  Union Hospital Affiliated to Fujian Medical University，Fujian，China

  PRINCIPAL INVESTIGATOR

• Yan Yu

  Heilongjiang Cancer Hospital，Heilongjiang，China

  PRINCIPAL INVESTIGATOR

• Jun G Zhang

  The First Affiliated Hospital of Zhengzhou University，Zhengzhou,China

  PRINCIPAL INVESTIGATOR

• Qiu Y Zhao

  Henan Cancer Hospital，Henan，China

  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: MD

Model Details: This is a open-label, multi-center, prospective, single-arm clinical trial

Study Record Dates

• First Submitted: March 15, 2021
• First Posted: March 22, 2021
• Study Start: July 9, 2021
• Primary Completion: June 15, 2024
• Study Completion: July 15, 2024
• Last Updated: April 22, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)