High-dose Furmonertinib Versus Osimertinib in Advanced EGFRm NSCLC Patients With Brain Metastases

NCT06319950 | Not Yet Recruiting Phase 2

• 1 other identifier: 20240229
• Study Type: interventional
• Target: 255
• Locations: 0 countries
• Sites: N/A

Brief Summary

The investigators were to explore whether high-dose Furmonertinib, compared with osimertinib, could achieve longer survival in patients with EGFR-mutated NSCLC with CNS metastasis.

Conditions

Lung Cancer, Nonsmall Cell

Keywords

non-small cell lung cancer (NSCLC); brain metastases; epidermal growth factor receptor (EGFR); tyrosine kinase inhibitors (TKI)

Outcome Measures

Primary Outcomes (1)

• progression free survival(PFS)

  The time from the start of randomization until the first occurrence of disease. progression or death from any cause, whichever occurs first.

  5 years from first patient randomized.

Secondary Outcomes (14)

• objective response rate(ORR)

  Duration of time from the start of treatment to the end of study, assessed up to 5 years

• Intracranial objective Response Rate(iORR)

  Duration of time from the start of treatment to the end of study, assessed up to 5 years

• Intracranial progression free survival(iPFS)

  5 years from first patient randomized.

• overal survival time(OS)

  5 years from first patient randomized.

• Disease control rate(DCR)

  Duration of time from the start of treatment to the end of study, assessed up to 5 years

Other Outcomes (1)

• Dynamic changes of ct-DNA

  Duration of time from the start of treatment to the end of study, assessed up to 5 years

Study Arms (2)

High-dose Furmonertinib group

EXPERIMENTAL

Furmonertinib, 160mg po qd

Drug: Furmonertinib

Osimertinib group

ACTIVE COMPARATOR

Osimertinib, 80mg po qd

Drug: Osimertinib

Interventions

Furmonertinib DRUG

Furmonertinib, 160mg po qd

Also known as: AST2818, alflutinib

High-dose Furmonertinib group

Osimertinib DRUG

Osimertinib，80mg po qd

Also known as: AZ9291

Osimertinib group

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female subjects aged \>=18 and \<=80 years old.
• Patients with histologically or cytologically confirmed NSCLC with adenocarcinoma or adenocarcinoma components predominant, and with central nervous system metastases (with measurable lesions).
• The tissue or blood sample is determined to be EGFR positive (including rare EGFR mutations) by testing by a tertiary Class A hospital or a qualified testing institution, and the tissue submitted for testing cannot be from a tumor lesion that has been treated with radiation, but can be used for a new lesion after local treatment.
• Patients who had not previously received systemic anti-tumor therapy for locally advanced or metastatic non-small cell lung cancer (patients who had received first-line chemotherapy but had not received TKIs could be enrolled). Patients who have undergone radical surgery, radical chemo-radiotherapy, or adjuvant therapy (chemotherapy, radiation) for early NSCLC may be enrolled if they later develop disease recurrence or metastasis.
• Stable brain metastases that do not require local treatment of brain metastases either immediately or planned during the study period.
• According to RECIST v1.1, enrolled patients should have at least one tumor lesion in all tumors that can meet the following requirements: they have not been treated with local therapy such as radiotherapy in the past, and can be accurately measured at baseline, and the longest diameter at baseline is ≥10mm (in the case of lymph nodes, the short diameter is ≥15mm). Lesions that have previously received local treatment (radiotherapy or other treatment) can only be measured if disease progression occurs more than 6 months after the end of treatment.
• ECOG PS 0-1, and with no deterioration during the first 2 weeks of the study and expected survival time of no less than 3 months.
• Patients should have sufficient bone marrow reserve function, and no liver, kidney, coagulation dysfunction, laboratory test values must meet the following conditions:
• Absolute neutrophil count ≥ 1.5×109/L, and white blood cell count ≥3×109/L;
• PLT ≥100×109/L;
• Hb ≥90g/L;
• Serum Cr ≤1.5×ULN and eGFR ≥50 mL/min;
• AST and ALT≤2.5×ULN (or AST and ALT≤5×ULN for patients with liver metastasis)
• In the absence of proven liver metastasis, TB ≤1.5×ULN (or TB ≤3×ULN for patients with liver metastasis or Gilbert syndrome;
• INR ≤1.5, and APTT ≤1.5×ULN.

You may not qualify if:

• Patients with the following treatments:
• Previous use of any EGFR TKIs therapy;
• Previously received systemic antitumor therapy (such as targeted therapy, biotherapy, immunotherapy, etc.) for advanced/metastatic non-small cell lung cancer;
• Standard chemotherapy within 28 days before the first administration of the study drug; The study received anti-tumor therapy with traditional Chinese medicine within 7 days before the first administration of the drug;
• Previous WBRT; Had received \>30% of bone marrow radiotherapy or extensive radiotherapy within 28 days prior to the first dose of the study drug; Local radiotherapy (e.g., thoracic and rib radiotherapy) or palliative radiotherapy for bone metastases within 7 days prior to initial administration of the study drug;
• Uncontrolled pleuroperitoneal effusion and pericardial effusion;
• Uncontrollable cancerous pain; Anesthetic painkillers did not reach a stable dose at the time of enrollment;
• Study major surgery within 28 days before the first administration of the drug ( major surgery refers to grade 3 and grade 4 surgery in Measures for the Clinical Application of Medical Technology in China, on May 1, 2009 );
• Has received a strong inducer or suppressor of CYP3A4 within 14 days prior to initial administration of the investigatory drug or requires continued treatment during the study period (including Chinese herbal medicine, see Appendix for a list of drugs);
• Patients who are receiving and require continued treatment during the study with drugs known to prolong the QTc interval or that may cause tip torsion ventricular tachycardia (see Appendix for a list of drugs);
• Participants who have participated in other clinical trials within 28 days prior to the first administration of the investigational drug (except non-interventional drug trials);
• Patients with primary malignant brain tumors and unstable brain metastases. Definition of unstable brain metastases: Patients with CNS complications who require emergency neurosurgical treatment (such as surgery); Patients with an equivalent dose of dexamethasone or more than 5mg of glucocorticoids, mannitol or diuretics to control symptoms of brain metastases should be administered within 14 days prior to the first dose; The first study looked at patients who had received local radiotherapy or gamma knife treatment within 14 days prior to administration. Patients with meningeal metastasis were excluded.
• Patients who have had or have a history of other malignancies within the past 5 years (except cured basal cell or squamous cell carcinoma of the skin, papillary carcinoma of the thyroid gland, carcinoma in situ of the cervix, and ductal carcinoma in situ of the breast).
• The patient had symptoms of spinal cord compression caused by the tumor.
• Clinically significant gastrointestinal dysfunction that may affect the intake, transport, or absorption of investigational drugs, such as inability to take oral drugs, difficult to control nausea or vomiting, a history of extensive gastrointestinal resection, Untreated recurrent diarrhea, atrophic gastritis (onset age less than 60 years), untreated stomach disease requiring long-term use of PPI acid suppressants, Crohn's disease, ulcerative colitis.

Sponsors & Collaborators

• Taizhou Hospital: lead

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Brain Neoplasms

Interventions

aflutinib; osimertinib

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

Central Study Contacts

Dongqing Lyu, MD

CONTACT

13867622009; lvdq@enzemed.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Physician

Study Record Dates

• First Submitted: March 1, 2024
• First Posted: March 20, 2024
• Study Start: April 1, 2024
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): December 30, 2026
• Last Updated: March 20, 2024

Record last verified: 2024-03