A Dose Exploration Study of Almonertinib for EGFRm NSCLC Patients With Brain/Leptomeningeal Metastasis (ARTISTRY)

A Dose Exploration Study of Almonertinib for Epidermal Growth Factor Receptor(EGFR)-Mutant Non-small-cell Lung Cancer(NSCLC) Patients With Newly Diagnosed or Recurrent Brain/Leptomeningeal Metastasis (ARTISTRY)

Almonertinib is a three-generation epidermal growth factor receptor tyrosine kinase inhibitor(EGFR-TKI), which has shown competitive potential in the second-line treatment against first-generation TKIs. This study aims to explore the efficacy and safety of different doses of almonertinib in the first-line and second-line treatment of brain metastases/meningeal metastases in NSCLC patients.

Study Overview

• Status: Recruiting
• Conditions: NSCLC; Brain Metastases; Leptomeningeal Metastasis
• Intervention / Treatment: Drug: almonertinib; Drug: LM-first line treatment; Drug: LM-second line treatment

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Huijuan Wang, MD; Phone Number: 18638561588; Email: 18638561588@163.com

Study Locations

• China
  • Henan
    • Zhengzhou, Henan, China, 450003
      • Recruiting
      • Henan Cancer Hospital
      • Contact: Wang Huijuan, MD; Phone Number: 18638561588; Email: 18638561588@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Queue 1

1. Male or female,age at least 18 years ;
2. Histologically confirmed patients with NSCLC brain metastases (including patients who have relapsed after previous treatment or newly diagnosed);
3. There must be at least one measurable brain lesion that has not been locally treated at the time of enrollment;
4. Patients who have not received other systemic treatment after the diagnosis of NSCLC brain metastasis, or patients who have received neoadjuvant therapy, adjuvant therapy, concurrent radiotherapy and chemotherapy, and local radiotherapy for more than 6 months;
5. Tumor tissue samples or blood are confirmed to be EGFR sensitive mutations (including exon 19 deletion or L858R) by ARMS;
6. The Eastern Cooperative Oncology Group (ECOG) physical status score is 0-2 and has not deteriorated in the previous 2 weeks, with a minimum expected survival of 12 weeks;
7. The patient is not required to have measurable systemic lesions; if there is, the lesions are required to be in at least one dimension (the largest diameter recorded by non-nodular lesions and the short axis of nodular lesions) ≥10mm by conventional techniques (CT, MRI) Can be accurately measured under the circumstances;
8. The subject himself voluntarily participated and signed an informed consent form.

Queue 2

1. Male or female,age at least 18 years ;
2. Histologically confirmed NSCLC patients (including patients who have relapsed after previous treatment or newly diagnosed);
3. Tumor cells found in cerebrospinal fluid or MRI showed clear meningeal enhancement and patients with dizziness/headache were included as selection criteria;
4. Patients who have not received other systemic treatment after being diagnosed with stage IV NSCLC, or patients who have received neoadjuvant therapy, adjuvant therapy, and concurrent radiotherapy and chemotherapy for more than 6 months;
5. The tumor tissue samples or blood are confirmed to be EGFR sensitive mutations (including exon 19 deletion or L858R) by ARMS;
6. The Eastern Cooperative Oncology Group (ECOG) physical status score is 0-2 and has not deteriorated in the previous 2 weeks, with a minimum expected survival of 12 weeks;
7. The patient is not required to have measurable systemic lesions; if there is, the lesions are required to be in at least one dimension (the largest diameter recorded by non-nodular lesions and the short axis of nodular lesions) ≥10mm by conventional techniques (CT, MRI) Can be accurately measured under the circumstances; The subjects themselves participated voluntarily and signed a written informed consent form.

Queue 3

1. Male or female,age at least 18 years ;
2. Histologically confirmed patients with stage IV NSCLC (including relapsed or newly diagnosed stage IV patients after previous treatment);
3. Patients with brain progression or brain lesions that have not resolved after the first/second generation EGFR-TKI treatment;
4. The patient must have at least one measurable brain lesion that has not been locally treated at the time of enrollment;
5. The tumor tissue samples or blood are confirmed to be EGFR sensitive mutations (including exon 19 deletion or L858R) by ARMS;
6. The Eastern Cooperative Oncology Group (ECOG) physical status score is 0-2 and has not deteriorated in the previous 2 weeks, with a minimum expected survival of 12 weeks;
7. The patient is not required to have measurable systemic lesions; if there is, the lesions are required to be in at least one dimension (the largest diameter recorded by non-nodular lesions and the short axis of nodular lesions) ≥10mm by conventional techniques (CT, MRI) Can be accurately measured under the circumstances;
8. The subject himself voluntarily participated and signed an informed consent form.

Exclusion Criteria:

1. the researchers believe that the risks faced by patients after entering the group are greater than those who benefit from them.
2. patients involved in any other clinical study.
3. patients with other malignant tumors.
4. A history of allergic reactions caused by compounds similar to almonertinib or its chemical composition.
5. pregnant or lactating women.
6. researchers should not participate in the study if they believe that patients cannot comply with the research procedures and requirements.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: almonertinib 110mg PO once daily	Drug: almonertinib; Patients was given a standard dose of 110mg/day of almonertinib, orally, and the first efficacy evaluation was carried out 4 weeks later. If the patient's lungs and/or other parts of the disease (PD) progress, then leave the group to receive other treatment; if the patient's lungs If the brain and other parts are stable or relieved and the brain has not progressed, continue the original dose treatment, and evaluate the effect every 8 weeks. Until the patient's lungs and/or other parts progress (PD), then leave the group to receive other treatment; if If the patient's lungs and other parts are stable or relieved and the brain is progressing, the dose of almonertinib can be increased to 165mg/day, orally ± radiotherapy (the investigator's decision), and then the efficacy will be evaluated every 8 weeks until the patient's lungs and/ Or there is progress (PD) in other parts, then the group will receive other treatment.
Experimental: almonertinib 160mg PO once daily	Drug: LM-first line treatment; Patients were given a standard dose of almonertinib 110 mg/day, orally, and the first efficacy evaluation was performed 4 weeks later. If there was no disease progression in two consecutive evaluations, the dose of almonertinib was increased to 165 mg /Day, oral ± radiotherapy (decided by the investigator), continue to evaluate the efficacy every 4 weeks until the patient progresses; if there is no disease progression in two consecutive assessments, the dose of almonertinib is increased to 220 mg/day, orally ± Radiotherapy treatment (determined by the investigator), continue to evaluate the efficacy every 4 weeks until the patient progresses.
Experimental: almonertinib 220mg PO once daily	Drug: LM-second line treatment; Patients were given a standard dose of almonertinib 110 mg/day, orally, and the first efficacy evaluation was performed 4 weeks later. If there was no disease progression in two consecutive evaluations, the dose of almonertinib was increased to 165 mg /Day, oral ± radiotherapy (decided by the investigator), continue to evaluate the efficacy every 4 weeks until the patient progresses; if there is no disease progression in two consecutive assessments, the dose of almonertinib is increased to 220 mg/day, orally ± Radiotherapy treatment (determined by the investigator), continue to evaluate the efficacy every 4 weeks until the patient progresses.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
iPFS	Intracranial progression-free survival (iPFS)	Up to approximately 3 years after the last patient is randomized

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DCR	Disease control rate (DCR)	Up to approximately 3 years after the last patient is randomized
PFS	progression-free period (PFS)	Up to approximately 3 years after the last patient is randomized
OS	overall survival (OS)	Up to approximately 3 years after the last patient is randomized

Collaborators and Investigators

• Sponsor: Henan Cancer Hospital
• Investigators: Principal Investigator: Huijuan Wang, MD, Henan Cancer Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 20, 2021
• Primary Completion (Anticipated): February 20, 2023
• Study Completion (Anticipated): February 20, 2024

Study Registration Dates

• First Submitted: January 27, 2021
• First Submitted That Met QC Criteria: February 28, 2021
• First Posted (Actual): March 3, 2021

Study Record Updates

• Last Update Posted (Actual): August 31, 2021
• Last Update Submitted That Met QC Criteria: August 25, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms; Neoplasms by Site; Neoplastic Processes; Central Nervous System Neoplasms; Nervous System Neoplasms; Meningeal Neoplasms; Neoplasm Metastasis; Brain Neoplasms; Neoplasms, Second Primary; Meningeal Carcinomatosis
• Other Study ID Numbers: HL-HS-006

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No