A Single-arm, Multicenter, Phase 2 Study of High-dose Furmonertinib Combined With Bevacizumab and Intrathecal Pemetrexed Chemotherapy in Patients With EGFR-mutated Non-small Cell Lung Cancer and Meningeal Metastasis

Plain English Summary

High-dose Furmonertinib Combined With Bevacizumab and Intrathecal Pemetrexed Chemotherapy in Patients With EGFR-mutated Non-small Cell Lung Cancer and Meningeal Metastasis is a Phase 2 clinical trial sponsored by Sun Yat-sen University studying Non-small Cell Lung Cancer Metastatic. This trial tests a combination of high-dose furmonertinib, bevacizumab, and chemotherapy injected into the spinal fluid. It is for patients with a specific type of non-small cell lung cancer (NSCLC) that has spread to the brain and has an EGFR mutation. Participation involves receiving the study drugs and regular medical check-ups, including imaging and lab tests. Standard treatments for this condition may include other chemotherapy, targeted therapies, or radiation therapy. The trial aims to enroll 46 participants.

Official Summary

the study conducted to evaluate the efficacy and safety of high-dose furmonertinib (160 mg qd) combined with bevacizumab and pemetrexed intrathecal chemotherapy in NSCLC patients with EGFR mutations and meningeal metastases.

Who Can Participate

Here is what you need to know about eligibility for this trial. Patients with non-small cell lung cancer (NSCLC) that has spread to the brain (meningeal metastasis). Must have specific EGFR gene mutations (exon 19 deletion, L858R, or T790M). Patients must be between 18 and 75 years old and in good general health (ECOG 0-1). Cannot have received systemic treatment after diagnosis of meningeal metastases. This trial is studying Non-small Cell Lung Cancer Metastatic, so participants generally need a confirmed diagnosis.

What They're Measuring

The primary outcome measures how long patients live without their cancer worsening in the brain, which is crucial for maintaining quality of life and neurological function. The specific primary outcome measures are: Intracranial progression-free survival (The time from receipt of study treatment to intracranial tumor PD or to death due to any cause,whichever came first, assessed up to 24 months). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 2, which tests whether the treatment actually works against the target condition. Phase 2 trials involve 100-300 patients and continue to monitor safety while evaluating effectiveness. This phase often tests different dosages to find the optimal amount. About 33% of Phase 2 drugs advance to Phase 3. If successful, the treatment will move to large-scale Phase 3 trials needed for FDA approval.

Why This Trial Matters

This trial addresses a critical need for effective treatments for lung cancer that has spread to the brain, a challenging complication for patients with EGFR-mutated NSCLC. Phase 2 success would typically lead to larger Phase 3 trials needed for regulatory approval. This research targets Non-small Cell Lung Cancer Metastatic, where improved treatment options are needed.

Investor Insight

This trial signals a focus on advanced lung cancer treatments, potentially targeting a significant market segment with unmet needs, with a moderate probability of success depending on trial results. Phase 2 trials have approximately a 15-20% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor about the specific risks and benefits of each drug in the combination therapy. Understand how the intrathecal chemotherapy (injection into spinal fluid) will be administered and what to expect. Be prepared for regular clinic visits for drug administration, blood tests, and imaging scans. The trial is being conducted at 1 site. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: NA
• Model: SINGLE_GROUP
• Masking: NONE
• Enrollment: 46 participants

Interventions

• DRUG: furmonertinib — furmonertinib (160mg, once a day, continuous administration); bevacizumab (7.5 mg/kg body weight, once every 3 weeks); Pemetrexed (50 mg intrathecal injection chemotherapy, once every 3 weeks).

Primary Outcomes

• Intracranial progression-free survival (The time from receipt of study treatment to intracranial tumor PD or to death due to any cause,whichever came first, assessed up to 24 months)

Secondary Outcomes

• systemic progression-free survival (The time from receipt of study treatment to systemic PD or to death due to any cause,whichever came first, assessed up to 24 months.)
• intracranial objective response rate (The number and percentage of objective response (PR+CR) of intracranial tumor at each time point after treatment, through study completion, an average of 12 months.)
• overall survival (The time interval between enrollment and death from any cause,,whichever came first, assessed up to 24 months.)
• safety and tolerability (adverse events will be reported and graded according to the National Cancer Institute (NCI) CTCAE version 5.0.,assessed up to 24 months.)

Full Eligibility Criteria

Inclusion Criteria:

* Histological or cytological localization is NSCLC;
* confirmed EGFR exon 19 deletion mutation(19del) or EGFR exon 21L858R mutation (L858R) or EGFR exon 20 T790M mutation (T790M)）;
* Clinical diagnosis of meningeal aggravation: clinical symptoms of intracranial hypertension (headache, dizziness, vomiting, etc.) + imaging confirmation (cerebral MRI diagnosis of meningeal aggravation) or cerebrospinal fluid cytology confirmation;
* for patients with symptoms who are considered to need temporary brain local. Treatment of cough receiving adrenal corticosteroids must be kept stable or reponse for at least 1 week before the first trial of the drug preparation;
* Newly diagnosed meningeal metastasis, including meningeal metastasis after previous brain surgery and/or local radiotherapy for solid metastatic disease;
* Patients did not received systemic treatment after diagnosed meningeal metastases.
* Obtain informed consent signed by the patient's legal representative;
* Aged ≥18 years and ≤75 years;
* Eastern Tourism Cooperation Group (ECOG) Physical condition evaluation 0-1;
* Life expectancy ≥12 week;
* Able to follow the requirements of the study protocol and confirmation procedures, and able to accept cranial wall medications;
* contraception.

Exclusion Criteria:

* Mixed non-small cell and small cell carcinoma, or squamous cell carcinoma as the main pathological type;
* history of hypersensitivity reaction to active or inactive excipients of furmonertinib, bevacizumab or pemetrexed or to drugs of similar structure or class to the investigational drug;
* Currently participating in an interventional clinical trial, or having received other study drugs or study devices within 4 weeks before the first study drug;
* Patients who have received solid organ or blood system transplantation;
* Patients with severe intracranial hypertension symptoms that cannot be relieved by discontinuation of dexamethasone and/or glycol treatment, or patients in intensive care;
* Ensure control of the patient's symptomatic pericardial, peritoneal, and pleural effusions;
* History of cancer in the last five years Other malignancies or a history of other malignancies;
* Recent active digestive events, such as duodenitis, ileitis, intestinal perforation, intestinal catheters, or other conditions that may cause gastrointestinal tract or perforation; or refractory vomiting, chronic gastrointestinal disease, inability to swallow study drugs, or previous colorectal cancer resection that prevents adequate drug absorption;
* The patient has a physique that is prone to Japanese language learning or has active Japanese language learning; Central squamous cell carcinoma or Patients at greater risk for hemoptysis; Any diamond event ≥ CTCAE grade 3, presence of open wounds, injuries or fractures in the 28th century before the first creation; if in the first Asthma was accepted 28 days before the organization meeting, the wound treatment should be evaluated by the interval period;
* History of arterial thromboembolism within the last 6 months, including vascular cerebral accident, myocardial infarction, transient cerebral contemplation;
* History of grade 4 venous thrombosis within the last 6 months, including fire embolism;
* The presence of any severe or uncontrolled systemic evidence, including difficult-to-control hypertension (systolic blood pressure ≥150 mmHg and/or diastolic blood pressure ≥100 mmHg), uncontrolled diabetes, etc.;
* Active infections include, for example, hepatitis B, hepatitis C, and human immunodeficiency virus (HIV) infections (including those requiring intravenous therapy, active hepatitis B infection includes patients with positive hepatitis B surface test based on serological assessment and hepatitis B virus DNA \>1000 copies/ml);
* previous history of interstitial lung disease, drug-induced interstitial lung disease, pneumonitis requiring steroid therapy, or any evidence of active interstitial lung disease;
* The first 28-day inspection of the drug preparation showed Lack of adequate bone marrow reserve or organ function （Within 2 weeks before blood test, No blood transfusion or blood products, granulocyte colony-stimulating factor or other hematopoietic stimulating factors were used for repair）:

  * Absolute neutrophil count \<1.5 × 109/L; continuous count \<100×109/L; hemoglobin \<90 g/L;
  * Alanine aminotransferase \> 2.5 times Upper limit of normal value (Upper limit of normal）; Aspartate aminotransferase\>2.5 times ULN; Total bilirubin\>1.5 times ULN; or liver transplant patients with AST and/or ALT \> 5× ULN;
  * Albumin \<30 g/L;
  * Serum creatinine \>1.5 times ULN, and Creatinine clearance \<50 mL/min （Measured or calculated by Cockcroft and Gault formula);
  * International normalized ratio (INR) \> 1.5,Partially activated zymogen time （APTT\>1.5 times Upper limit of normal;
  * Urine protein ≥++, and 24-hour protein \>2.0g;
* Any of the following Bishop criteria:

  * Clinically signi

Trial Locations

• Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China

Frequently Asked Questions

Related Conditions

• Non-small Cell Lung Cancer
• EGFR Mutation
• Meningeal Metastasis
• Brain Metastasis
• Lung Cancer
• Oncology
• Targeted Therapy
• Chemotherapy
• Bevacizumab
• Pemetrexed

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