Non Small Cell Lung CancerPhase 2FLAME-1NCT06971406
High-Dose Firmonertinib Combined With Bevacizumab and Intrathecal Pemetrexed in the Treatment of EGFR-Mutated Non-Small Cell Lung Cancer With Leptomeningeal Metastasis
A Phase 2 study testing Combination therapy prospective cohort in people with Non Small Cell Lung Cancer and EGFR Mutation, run by Qiming Wang.
Trial summary
Primary Objective: To evaluate the efficacy of high-dose firmonertinib combined with bevacizumab and intrathecal pemetrexed in EGFR Ex19del/L858R-mutated non-small cell lung cancer (NSCLC) with leptomeningeal metastasis (LM), as measured by Overall Survival (OS). Secondary Objectives: 1. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non Small Cell Lung Cancer, EGFR Mutation, Leptomeningeal Metastases
- What is being tested?
- Combination therapy prospective cohort
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- No sites listed yet
- Study dates
- 15 May 2025to 1 Jun 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Have obtained written informed consent from the patient or his or her legal representative.
- Age ≥18 years, male or female.
- Histologically or cytologically confirmed diagnosis of non-small cell lung cancer (NSCLC).
- EGFR mutations confirmed by genetic testing (EGFR Ex19del/L858R/Ex20ins/PACC/L861Q).
- Leptomeningeal metastasis diagnosed by comprehensive clinical assessment according to "EANO-ESMO" diagnostic criteria, including symptom evaluation, imaging assessment, and/or cerebrospinal fluid (CSF) cytopathological evaluation.
- Both treatment-naïve leptomeningeal metastasis patients and those who progressed after standard antitumor therapies in clinical practice are eligible. ≤3 prior lines of therapy allowed (patients with >3 prior lines may enroll in the real-world study cohort).
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- ECOG PS 0-2 (patients with ECOG PS >2 may enroll in the real-world study cohort).
- Prior radiotherapy or surgical treatment targeting the central nervous system (CNS) is permitted.
- Patients with CNS symptoms/signs are allowed if these manifestations are not life-threatening.
- Patients previously treated with standard-dose third-generation EGFR TKIs, pemetrexed intravenous infusion, or bevacizumab are permitted.
- Adequate organ function:
- Absolute neutrophil count (ANC) ≥1.5×10^9/L, platelets ≥75×10^9/L, hemoglobin ≥80g/L Total bilirubin ≤1.5×ULN, AST/ALT ≤2.5×ULN (≤3×ULN for bilirubin and ≤5×ULN for AST/ALT in cases with liver metastasis) Serum creatinine ≤1.5×ULN or creatinine clearance ≥50 mL/min (calculated by Cockcroft-Gault formula).
- Sexually active males or females of childbearing potential must use highly effective contraception (e.g., oral contraceptives, IUD, abstinence, or barrier methods with spermicide) during the trial and for 12 months after treatment completion.
Who cannot join
- Diagnosis of other malignancies within the past 5 years or history of other malignancies (except adequately controlled basal cell carcinoma of the skin, cervical carcinoma in situ, or ductal carcinoma in situ of the breast).
- Severe gastrointestinal disorders affecting drug administration or absorption, including but not limited to peptic ulcer disease, inflammatory bowel disease, etc.
- Known or suspected hypersensitivity to the investigational drugs (Firmonertinib, Bevacizumab, Pemetrexed) or any of their excipients.
- Prior treatment with high-dose third-generation EGFR TKI or intrathecal chemotherapy with Pemetrexed.
- Evidence of any severe or uncontrolled systemic diseases, including uncontrolled hypertension, diabetes, active bleeding, or active infections (e.g., hepatitis B/C, HIV), which in the investigator's judgment may jeopardize patient participation or protocol compliance.
- History of steroid-requiring radiation pneumonitis or any evidence of active interstitial lung disease.
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- Clinically significant cardiac arrhythmias (e.g., QTc interval >500 ms) or heart failure (left ventricular ejection fraction <50%).
- Pregnant or lactating women.
- Patients currently participating in or having received investigational drug therapy within 2 weeks prior to enrollment.
- Other severe acute/chronic medical or psychiatric conditions or laboratory abnormalities that, in the investigator's opinion, may increase study-related risks, interfere with result interpretation, or compromise the patient's ability to complete the study or adhere to protocol requirements.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: A Multicenter, Prospective Phase II Clinical Study of High-Dose Firmonertinib Combined With Bevacizumab and Intrathecal Pemetrexed in the Treatment of EGFR-Mutated Non-Small Cell Lung Cancer With Leptomeningeal Metastasis
Primary Objective:
To evaluate the efficacy of high-dose firmonertinib combined with bevacizumab and intrathecal pemetrexed in EGFR Ex19del/L858R-mutated non-small cell lung cancer (NSCLC) with leptomeningeal metastasis (LM), as measured by Overall Survival (OS).
Read more
Secondary Objectives:
- To assess the efficacy of this regimen in EGFR Ex20ins/PACC/L861Q-mutated NSCLC with LM.
- To further evaluate therapeutic outcomes across cohorts, including:
- Time to Treatment Failure (TTF)
- Leptomeningeal Objective Response Rate (ORR-LM)
- Clinical Response Rate
- To analyze the impact of this regimen on *quality of life* using standardized metrics:
- EORTC QLQ-C30
- EORTC QLQ-LC13
- To assess safety profiles across cohorts, focusing on:
- Incidence and severity of adverse events (AEs) graded per *CTCAE v5.0*
- Frequency of treatment-related toxicities
Exploratory Objectives:
To investigate correlations between dynamic changes in:
- Plasma-derived circulating tumor DNA (ctDNA)
- Cerebrospinal fluid-derived cell-free DNA (cfDNA) and clinical outcomes through comparative analysis of genomic profiling and epigenetic signatures before and after treatment.
- Being tested
- Combination therapy prospective cohort
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Meningeal Carcinomatosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Combination therapy prospective cohortDrug
high-dose firmonertinib (240 mg, daily), bevacizumab (15 mg/kg, every 3 weeks), and pemetrexed (50 mg, intrathecal chemotherapy C1d1d5, then every 3 weeks)
| Study group | Role | What they receive |
|---|---|---|
| prospective cohort | Experimental | high-dose firmonertinib (240 mg, daily), bevacizumab (15 mg/kg, every 3 weeks), and pemetrexed (50 mg, intrathecal chemotherapy,C1 d1d5,then every 3 weeks) Receives: Drug: Combination therapy prospective cohort |
What is being measured
The primary outcome is the main question the study is designed to answer.
OS（EGFR Ex19del/L858R）
overall survive time （EGFR Ex19del/L858R）
Measured: the time between the date of enrollment and the date of death from any cause for EGFR Ex19del/L858R NSCLC with leptomeningeal metastases(up to 36 months)
Secondary outcomes (6)
OS（EGFREx20ins/PACC/L861Q）
overall survive time（EGFREx20ins/PACC/L861Q）
Measured: the time between the date of enrollment and the date of death from any cause for EGFREx20ins/PACC/L861Q NSCLC with leptomeningeal metastases(up to 36 months)
TTF
time to treatment failure:The time interval from the start of the triple therapy to treatment failure
Measured: up to 24 months
ORR-LM
Objective Response Rate in Leptomeningeal Metastases：the proportion of patients whose leptomeningeal lesions achieve a complete response (CR) or partial response (PR) during the study period from the first administration of the study drug until leptomeningeal disease progression
Measured: up to 24 months
CRR
Clinical response rate：the proportion of patients whose CR, OR, or PR lasts for at least one week
Measured: up to 24 months
Quality of life assessment (EORTC QLQ-C30, EORTC QLQ-LC13)
EORTC QLQ-C30(European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire - 30 items, score:30-126, Higher scores indicate worse quality of life) and EORTC QLQ-LC13(European Organization for Research and Treatment of Cancer Quality of Life Lung Module 13 items) were used to assess the quality of life, scores were normalized to 0-100, with high scores in the symptom domain indicating severe symptoms and high scores in the functional domain indicating good functioning
Measured: At the end of every 2 cycles(each cycle is 21 days)
AE
AEs (Adverse events)were graded according to CTCAE v5.0 every two cycles after enrollment
Measured: At the end of every 2 cycles(each cycle is 21 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 May 2025
- Study start15 May 2025 (estimated)
- Primary completion1 Jan 2027 (estimated)
- Study completion1 Jun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non Small Cell Lung CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Qiming Wang
- Sponsor type
- Other government
- Responsible party
- Sponsor-investigator, Qiming Wang, Henan Cancer Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06971406
- Sponsor's protocol ID
- 2025-083
- Acronym
- FLAME-1
- Status last verified
- May 2025
- First submitted
- 27 Apr 2025
- Last updated
- 14 May 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Prospective Phase II Clinical Study of High-Dose Firmonertinib Combined With Bevacizumab and Intrathecal Pemetrexed in the Treatment of EGFR-Mutated Non-Small Cell Lung Cancer With Leptomeningeal Metastasis
- ClinicalTrials.gov ID
- NCT06971406
- Acronym / sponsor ID
- FLAME-1 / 2025-083
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Qiming WangOther government
- Study start
- 15 May 2025 (estimated)
- Primary completion
- 1 Jan 2027 (estimated)
- Study completion
- 1 Jun 2027 (estimated)
- First posted
- 14 May 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Primary Objective:
To evaluate the efficacy of high-dose firmonertinib combined with bevacizumab and intrathecal pemetrexed in EGFR Ex19del/L858R-mutated non-small cell lung cancer (NSCLC) with leptomeningeal metastasis (LM), as measured by Overall Survival (OS).
Secondary Objectives:
- To assess the efficacy of this regimen in EGFR Ex20ins/PACC/L861Q-mutated NSCLC with LM.
- To further evaluate therapeutic outcomes across cohorts, including:
- Time to Treatment Failure (TTF)
- Leptomeningeal Objective Response Rate (ORR-LM)
- Clinical Response Rate
- To analyze the impact of this regimen on *quality of life* using standardized metrics:
- EORTC QLQ-C30
- EORTC QLQ-LC13
- To assess safety profiles across cohorts, focusing on:
- Incidence and severity of adverse events (AEs) graded per *CTCAE v5.0*
- Frequency of treatment-related toxicities
Exploratory Objectives:
To investigate correlations between dynamic changes in:
- Plasma-derived circulating tumor DNA (ctDNA)
- Cerebrospinal fluid-derived cell-free DNA (cfDNA) and clinical outcomes through comparative analysis of genomic profiling and epigenetic signatures before and after treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| prospective cohort | Experimental | Drug: Combination therapy prospective cohorthigh-dose firmonertinib (240 mg, daily), bevacizumab (15 mg/kg, every 3 weeks), and pemetrexed (50 mg, intrathecal chemotherapy,C1 d1d5,then every 3 weeks) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Have obtained written informed consent from the patient or his or her legal representative.
- Age ≥18 years, male or female.
- Histologically or cytologically confirmed diagnosis of non-small cell lung cancer (NSCLC).
- EGFR mutations confirmed by genetic testing (EGFR Ex19del/L858R/Ex20ins/PACC/L861Q).
- Leptomeningeal metastasis diagnosed by comprehensive clinical assessment according to "EANO-ESMO" diagnostic criteria, including symptom evaluation, imaging assessment, and/or cerebrospinal fluid (CSF) cytopathological evaluation.
Key exclusion criteria (10 listed)
- Diagnosis of other malignancies within the past 5 years or history of other malignancies (except adequately controlled basal cell carcinoma of the skin, cervical carcinoma in situ, or ductal carcinoma in situ of the breast).
- Severe gastrointestinal disorders affecting drug administration or absorption, including but not limited to peptic ulcer disease, inflammatory bowel disease, etc.
- Known or suspected hypersensitivity to the investigational drugs (Firmonertinib, Bevacizumab, Pemetrexed) or any of their excipients.
- Prior treatment with high-dose third-generation EGFR TKI or intrathecal chemotherapy with Pemetrexed.
- Evidence of any severe or uncontrolled systemic diseases, including uncontrolled hypertension, diabetes, active bleeding, or active infections (e.g., hepatitis B/C, HIV), which in the investigator's judgment may jeopardize patient participation or protocol compliance.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Combination therapy prospective cohorthigh-dose firmonertinib (240 mg, daily), bevacizumab (15 mg/kg, every 3 weeks), and pemetrexed (50 mg, intrathecal chemotherapy C1d1d5, then every 3 weeks) | Drug | prospective cohort |
Primary outcome
OS（EGFR Ex19del/L858R）
Time frame: the time between the date of enrollment and the date of death from any cause for EGFR Ex19del/L858R NSCLC with leptomeningeal metastases(up to 36 months)
overall survive time （EGFR Ex19del/L858R）
6 secondary outcomes
OS（EGFREx20ins/PACC/L861Q）
Time frame: the time between the date of enrollment and the date of death from any cause for EGFREx20ins/PACC/L861Q NSCLC with leptomeningeal metastases(up to 36 months)
TTF
Time frame: up to 24 months
ORR-LM
Time frame: up to 24 months
CRR
Time frame: up to 24 months
Quality of life assessment (EORTC QLQ-C30, EORTC QLQ-LC13)
Time frame: At the end of every 2 cycles(each cycle is 21 days)
AE
Time frame: At the end of every 2 cycles(each cycle is 21 days)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 May 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Combination therapy prospective cohort in people with Non Small Cell Lung Cancer and EGFR Mutation, run by Qiming Wang.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 14 May 2025. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Haiyang Chen (+86 15003879297, chenocean017@126.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
OS（EGFR Ex19del/L858R） (time frame: the time between the date of enrollment and the date of death from any cause for EGFR Ex19del/L858R NSCLC with leptomeningeal metastases(up to 36 months)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 May 2025.