High-dose furmonertinib for treating lung cancer with brain metastases

A Single Arm, Multicenter Clinical Study of High-dose Furmonertinib in First-line Treatment of EGFR Mutated NSCLC With Central Nervous System (CNS) Metastases

This study is testing if a high dose of furmonertinib can help people with lung cancer that has spread to the brain feel better and live longer.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 40 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Hunan Province Tumor Hospital (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy, radiation, furmonertinib
• Locations: 1 site (Changsha, Hunan)
• Trial ID: NCT05379803 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the efficacy and safety of high-dose furmonertinib (160mg/day) as a first-line treatment for patients with EGFR mutated non-small cell lung cancer (NSCLC) who also have central nervous system (CNS) metastases. The study is a single-arm, multicenter trial that aims to recruit approximately 40 patients in China. Participants will receive the treatment and be monitored for outcomes related to progression-free survival and overall response rate. This approach is novel as it explores the use of furmonertinib in a first-line setting for this specific patient population.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with confirmed EGFR mutations and measurable CNS metastatic lesions.

Not a fit: Patients with previously treated advanced/metastatic NSCLC or those without CNS metastases may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve outcomes for patients with EGFR mutated NSCLC and CNS metastases.

How similar studies have performed: While high-dose furmonertinib has shown promise in second-line treatment for EGFR T790M mutated NSCLC, this first-line application in patients with CNS metastases is novel and has not been previously reported.

Eligibility criteria

Inclusion Criteria:

* Signed written informed consent before any study-related procedure.
* Age ≥ 18 years.
* ECOG PS of 0 to 1 at screening,and with no clinically significant deterioration in the previous 2 weeks.
* Expected survival ≥12 weeks.
* Histologically or cytologically confirmed metastatic Non-Small Cell Lung Cancer (International Association for the Study of Lung Cancer and Joint Committee on the American Classification of Cancer, TNM Lung cancer stage 8). Documented validated results from local testing of either tumor tissue or blood confirming the presence of EGFR 19del or exon 21del L858R mutation. These mutations above may exist alone or together.
* According to RECIST 1.1, patients must have at least one central nervous system (CNS) metastatic tumor lesion at baseline that meets the following requirements: accurately and repeatably measurable at baseline, have no radiotherapy or biopsy.
* Patients who have untreated for advanced/metastatic non-small cell lung cancer, including chemotherapy, biological therapy, targeted therapy, immunotherapy, or experimental therapy, prior to initiation of study drug therapy. Patients who have received adjuvant therapy or neoadjuvant therapy (chemotherapy and/or radiotherapy) are allowed to enroll if there is no progression within 6 months of treatment. Patients who have received topical therapy (radiotherapy or perfusion therapy) are allowed to enroll if the lesion within the local therapeutic area is non-targeted.
* For premenopausal women with childbearing potential, a pregnancy test must be performed within 14 days before the first dose, and the pregnancy test (blood or urine test) must be negative; female subjects must not be lactating;
* Willing to use contraception.
* Voluntary and agree to follow the study treatment protocol as well as follow-up plan, and can accept the oral medicine treatment.

Exclusion Criteria:

* Small cell lung carcinoma;
* History of hypersensitivity to active or inactive excipients of investigational agent with a similar chemical structure.
* Confirmed EGFR 20 exon insertion mutations at any time after the initial diagnosis.
* Patient who receive prior treatment including any of the following:
* Any Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI).
* The patients who have received intrapleural perfusion therapy can only be enrolled 28 days or more after the pleural effusion is stable;
* Major surgery within 4 weeks of the first dose of investigational agent.
* Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of investigational agent;
* CYP3A4 strong inhibitor or strong inducer is used within 7 days prior to the first dose, or need to receive these drugs during the study period.
* Traditional Chinese medicine and traditional Chinese medicine preparations with anti-tumor as indications and with adjuvant treatment of tumor is used within 7 days prior to the first dose, or need to receive these drugs during the study period.
* Patients who are receiving drugs known to prolong QTc interval or may cause torsade de pointe and need to continue to receive these drugs during the study period.
* The time from the treatment with any other investigational product or its analogue to the first dose does not exceed 5 half-lives of the drug or 14 days, whichever is longer.
* Prior treatment with any systemic anti-cancer therapy for advanced Non-Small Cell Lung Cancer (NSCLC) including chemotherapy, biologic therapy, target therapy, immunotherapy, or any investigational drug, except neoadjuvant or adjuvant therapy before 6 months prior to the first dose investigational treatment.
* At the beginning of study treatment, any unresolved toxic reaction to prior treatment is present, which exceeds Grade 1 in accordance with Common Terminology Criteria for Adverse Events (CTCAE) (except for alopecia), and exceeds Grade 2 for prior platinum treatment-related neuropathy.
* Spinal cord compression; symptomatic and unstable brain metastases, except for those patients who have completed definitive therapy, are not on steroids, and have a stable neurological status for at least 2 weeks after completion of the definitive therapy and steroids.
* Diagnosed other malignant tumors or had a history of other malignant tumors in last 5 years, except for skin basal cell carcinoma, cervical carcinoma in situ and breast ductal carcinoma in situ which have been effectively controlled;
* Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product, or previous significant bowel resection that would preclude adequate absorption of investigational agent.
* Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension, active bleeding diatheses, and active infection, which in the Investigator's opinion makes it undesirable for the patient to participate in the trial.
* Past medical history of Interstitial Lung Disease (ILD), drug-induced Interstitial Lung Disease, radiation pneumonitis that required steroid treatment, or any evidence of clinically active Interstitial Lung Disease.
* Any evidence of corneal injury:
* Inadequate bone marrow reserve or organ function.
* QT prolongation or any clinically important abnormalities in rhythm and heart function.
* Patients who may have poor compliance with the research procedures and requirements, etc., as judged by investigators.
* Pregnancy or lactation.

Where this trial is running

Changsha, Hunan

• Hunan Cancer hospital — Changsha, Hunan, China (Recruiting)

Study contacts

• Study coordinator: Nong C Yang, MD

Conditions Non-Small Cell Lung Cancer