Leptomeningeal Metastasis From Lung CancerPhase 1/2NCT07744529
Amivantamab Combined With Intrathecal Pemetrexed for LM From EGFR-Mutated Lung Adenocarcinoma
A Phase 1/2 study testing Amivantamab+ systemic/ intrathecal Pemetrexed in people with Leptomeningeal Metastasis From Lung Cancer, run by Second Affiliated Hospital, Zhejiang University, School of Medicine at 1 site in China.
Trial summary
The goal of this clinical trial is to learn whether amivantamab combined with intrathecal pemetrexed is safe and may help treat leptomeningeal metastasis in adults with EGFR-mutant lung adenocarcinoma. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Leptomeningeal Metastasis From Lung Cancer
- What is being tested?
- Amivantamab+ systemic/ intrathecal Pemetrexed
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteChina
- Study dates
- 28 May 2026to 28 May 2028
- Phase
- Phase 1/2
- 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
- Voluntary participation in the clinical study: fully understands and is informed of this study and signs the written informed consent form; is willing and able to complete all trial procedures.
- Age: >=18 years; male or female.
- Patients with EGFR-mutated lung adenocarcinoma with leptomeningeal metastasis diagnosed according to the EANO-ESMO guidelines.
- Expected survival of at least 3 months.
- Adequate organ and bone marrow function, with no severe hematopoietic abnormality and no severe cardiac, pulmonary, hepatic or renal dysfunction or immunodeficiency (within 14 days before use of study drug, no blood transfusion, granulocyte colony-stimulating factor or other relevant medical support):
- Complete blood count: absolute neutrophil count (ANC) >=1.5 x 10^9/L (1500/mm^3), platelets >=75 x 10^9/L, hemoglobin >=9 g/dL (if bone marrow is involved, platelets >=50 x 10^9/L, ANC >=1.0 x 10^9/L and hemoglobin >=8 g/dL).
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- Liver function: serum bilirubin <=1.5 x upper limit of normal (ULN), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <=1.5 x ULN (if there is liver involvement, AST and ALT <=5 x ULN are allowed).
- Renal function: serum creatinine <=1.5 x ULN.
- Coagulation function: INR <=1.5 x ULN; PT and APTT <=1.5 x ULN (unless the subject is receiving anticoagulant therapy and PT and APTT are within the expected range of anticoagulant treatment at screening).
- Left ventricular ejection fraction (LVEF) in cardiac function examination >=50%.
- Negative serum pregnancy test, and effective contraception from signing the informed consent form until 6 months after the last chemotherapy dose.
- Thyroid-stimulating hormone (TSH), free thyroxine (FT4) or free triiodothyronine (FT3) within +/-10% of the normal range.
- Ophthalmic examination, including dilated fundus examination, slit-lamp examination and color fundus photography.
Who cannot join
- Currently participating in another clinical study, or less than 4 weeks between the first dose of the study drug and the end of treatment in a previous clinical study.
- History of other malignancies within the past 5 years.
- Patients who have received CNS-directed prophylactic treatment.
- Patients with known history of human immunodeficiency virus (HIV) infection and/or acquired immunodeficiency syndrome.
- Patients with active autoimmune disease or a history of autoimmune disease with a high risk of recurrence, including but not limited to immune-related neuropathy, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome, myasthenia gravis, systemic lupus erythematosus, connective tissue disease, scleroderma, inflammatory bowel cancer (including Crohn disease and ulcerative colitis), autoimmune hepatitis, toxic epidermal necrolysis or Stevens-Johnson syndrome.
- Patients with active chronic hepatitis B or active hepatitis C. Patients who are positive for hepatitis B surface antigen or hepatitis C virus antibody during screening may be enrolled only after further HBV DNA titer testing (not higher than 1000 IU/mL) and HCV RNA testing (not exceeding the lower limit of detection of the assay), and after active hepatitis B or hepatitis C infection requiring treatment has been excluded. Hepatitis B virus carriers, patients with stable hepatitis B after drug treatment and patients with cured hepatitis C may be enrolled.
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- Active pulmonary tuberculosis.
- Current interstitial lung disease or infectious pneumonia.
- Active infection requiring systemic anti-infective therapy, including but not limited to bacterial, fungal or viral infection.
- Within 6 months before screening, New York Heart Association (NYHA) class III or IV heart failure, unstable angina, severe poorly controlled ventricular arrhythmia, or electrocardiographic evidence of acute ischemia or myocardial infarction.
- QTcF interval >480 msec, unless secondary to bundle branch block.
- Uncontrolled comorbid disease, including but not limited to uncontrolled hypertension, active peptic ulcer or bleeding disorder.
- History of psychiatric illness; incapacity or limited capacity for civil conduct.
- In the judgment of the investigator, the patient's underlying condition may increase the risk of receiving study drug treatment or confound the occurrence and assessment of toxic reactions.
- Other patients whom the investigator considers unsuitable for participation in this study.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
The Second Affiliated Hospital,School of Medicine,Zhejiang University
Hangzhou, Zhejiang, 310000
About this study
Official title: A Single-Arm Phase II Exploratory Clinical Study of Amivantamab Combined With Intrathecal Pemetrexed for Leptomeningeal Metastasis From EGFR-Mutated Lung Adenocarcinoma
The goal of this clinical trial is to learn whether amivantamab combined with intrathecal pemetrexed is safe and may help treat leptomeningeal metastasis in adults with EGFR-mutant lung adenocarcinoma. Leptomeningeal metastasis occurs when cancer cells spread to the membranes surrounding the brain and spinal cord or to the cerebrospinal fluid. It is a serious complication of advanced lung cancer and is difficult to treat because many systemic drugs do not reach high enough levels in the cerebrospinal fluid.
The main questions this study aims to answer are:
Read more
What medical problems do participants have when receiving amivantamab combined with intrathecal pemetrexed? How long do participants live without their disease getting worse after receiving this treatment? How long do participants survive after starting this treatment?
Participants will:
Receive amivantamab by intravenous infusion according to the study schedule. Receive intrathecal pemetrexed, together with dexamethasone and normal saline, once every week.
Continue their original EGFR tyrosine kinase inhibitor treatment as determined by the study doctor.
Have cerebrospinal fluid pressure measured and cerebrospinal fluid samples collected before each intrathecal treatment.
Have tests of cerebrospinal fluid, including routine tests, biochemical tests, tumor markers, albumin, IgG, and cytology.
Have imaging tests, including enhanced MRI, about every 3 months to check the disease.
Be followed by clinic visits and/or telephone calls to collect information about survival, disease status, side effects, and any later cancer treatments.
- Being tested
- Amivantamab+ systemic/ intrathecal Pemetrexed
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Amivantamab+ systemic/ intrathecal PemetrexedDrug
Amivantamab dosing regimen: once weekly in the first month, 350 mg each time; no dosing is required in weeks 5 and 6. Starting from week 7, 700 mg each time once every 3 weeks. Systemic pemetrexed dosing regimen: day 1 of week 1, week 4, week 7 and once every 3 weeks thereafter, 500 mg/m2. Intrathecal injection shall be performed by personnel qualified to perform intrathecal injection (personnel of the Department of Radiation Oncology of our hospital holding standardized residency training certificates).
| Study group | Role | What they receive |
|---|---|---|
| Treatment group | Experimental | Subjects will receive a comprehensive treatment regimen of amivantamab combined with systemic pemetrexed chemotherapy + intrathecal pemetrexed. Amivantamab dosing regimen: once weekly in the first month, 350 mg each time; no dosing is required in weeks 5 and 6. Starting from week 7, 700 mg each time once every 3 weeks. Systemic pemetrexed dosing regimen: day 1 of week 1, week 4, week 7 and once every 3 weeks thereafter, 500 mg/m2. Intrathecal injection shall be performed by personnel qualified to perform intrathecal injection (personnel of the Department of Radiation Oncology of our hospital holding standardized residency training certificates). Receives: Drug: Amivantamab+ systemic/ intrathecal Pemetrexed |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants with Treatment-Related Adverse Events as Assessed by CTCAE v5.0"
The primary safety analysis will be conducted in subjects who develop toxicities (as defined according to CTCAE criteria). Safety will be evaluated using CTCAE version 5.0 through reported adverse events. The relationship between adverse events and the drug, time of onset, duration of the event, resolution of the event and any concomitant medication will be recorded. Adverse events (AEs) will be analyzed, including but not limited to all AEs, serious adverse events (SAEs), fatal AEs and laboratory changes.
Measured: 2 year
Secondary outcomes (8)
ORR
The percentage of patients who received response after treatment accessed by RANO-LM criteria
Measured: 2 year
DCR
The percentage of patients with response and SD accessed by RANO-LM criteria after treatment among the evaluable cases
Measured: 2 year
Overall survival
The time from the beginning of the patient's treatment (or disease diagnosis) to death for any reason.
Measured: 2 year
Progression-Free Survival
The time between the start of treatment and the progression of the tumor or the death of the patient for any reason.
Measured: 2 year
3-month OS rate
Evaluate the survival rate of patients after 3 months of treatment
Measured: 3 months
6-month OS rate
Evaluate the survival rate of patients after 6 months of treatment
Measured: 6 months
9-month OS rate
Evaluate the survival rate of patients after 9 months of treatment
Measured: 9 months
1-year OS rate
Evaluate the survival rate of patients after 1 year of treatment
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Aug 2026
- Study start28 May 2026
- Primary completion28 May 2028 (estimated)
- Study completion28 May 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Leptomeningeal Metastasis From Lung CancerStudies of the same condition, open and under way.
- More trials run by Second Affiliated Hospital, Zhejiang University, School of MedicineThe sponsor's other registered studies.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Bicheng Zhang, Second Affiliated Hospital, Zhejiang University, School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07744529
- Sponsor's protocol ID
- Y2026-0871
- Status last verified
- Aug 2026
- First submitted
- 13 Jul 2026
- Last updated
- 4 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single-Arm Phase II Exploratory Clinical Study of Amivantamab Combined With Intrathecal Pemetrexed for Leptomeningeal Metastasis From EGFR-Mutated Lung Adenocarcinoma
- ClinicalTrials.gov ID
- NCT07744529
- Acronym / sponsor ID
- Y2026-0871
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 15 participants (estimated)
- Lead sponsor
- Second Affiliated Hospital, Zhejiang University, School of MedicineUniversity, hospital or other
- Study start
- 28 May 2026 (actual)
- Primary completion
- 28 May 2028 (estimated)
- Study completion
- 28 May 2028 (estimated)
- First posted
- 4 Aug 2026 (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.
The goal of this clinical trial is to learn whether amivantamab combined with intrathecal pemetrexed is safe and may help treat leptomeningeal metastasis in adults with EGFR-mutant lung adenocarcinoma. Leptomeningeal metastasis occurs when cancer cells spread to the membranes surrounding the brain and spinal cord or to the cerebrospinal fluid. It is a serious complication of advanced lung cancer and is difficult to treat because many systemic drugs do not reach high enough levels in the cerebrospinal fluid.
The main questions this study aims to answer are:
What medical problems do participants have when receiving amivantamab combined with intrathecal pemetrexed? How long do participants live without their disease getting worse after receiving this treatment? How long do participants survive after starting this treatment?
Participants will:
Receive amivantamab by intravenous infusion according to the study schedule. Receive intrathecal pemetrexed, together with dexamethasone and normal saline, once every week.
Continue their original EGFR tyrosine kinase inhibitor treatment as determined by the study doctor.
Have cerebrospinal fluid pressure measured and cerebrospinal fluid samples collected before each intrathecal treatment.
Have tests of cerebrospinal fluid, including routine tests, biochemical tests, tumor markers, albumin, IgG, and cytology.
Have imaging tests, including enhanced MRI, about every 3 months to check the disease.
Be followed by clinic visits and/or telephone calls to collect information about survival, disease status, side effects, and any later cancer treatments.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment group | Experimental | Drug: Amivantamab+ systemic/ intrathecal PemetrexedSubjects will receive a comprehensive treatment regimen of amivantamab combined with systemic pemetrexed chemotherapy + intrathecal pemetrexed. Amivantamab dosing regimen: once weekly in the first month, 350 mg each time; no dosing is required in weeks 5 and 6. Starting from week 7, 700 mg each time once every 3 weeks. Systemic pemetrexed dosing regimen: day 1 of week 1, week 4, week 7 and once every 3 weeks thereafter, 500 mg/m2. Intrathecal injection shall be performed by personnel qualified to perform intrathecal injection (personnel of the Department of Radiation Oncology of our hospital holding standardized residency training certificates). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Voluntary participation in the clinical study: fully understands and is informed of this study and signs the written informed consent form; is willing and able to complete all trial procedures.
- Age: >=18 years; male or female.
- Patients with EGFR-mutated lung adenocarcinoma with leptomeningeal metastasis diagnosed according to the EANO-ESMO guidelines.
- Expected survival of at least 3 months.
- Adequate organ and bone marrow function, with no severe hematopoietic abnormality and no severe cardiac, pulmonary, hepatic or renal dysfunction or immunodeficiency (within 14 days before use of study drug, no blood transfusion, granulocyte colony-stimulating factor or other relevant medical support):
Key exclusion criteria (15 listed)
- Currently participating in another clinical study, or less than 4 weeks between the first dose of the study drug and the end of treatment in a previous clinical study.
- History of other malignancies within the past 5 years.
- Patients who have received CNS-directed prophylactic treatment.
- Patients with known history of human immunodeficiency virus (HIV) infection and/or acquired immunodeficiency syndrome.
- Patients with active autoimmune disease or a history of autoimmune disease with a high risk of recurrence, including but not limited to immune-related neuropathy, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome, myasthenia gravis, systemic lupus erythematosus, connective tissue disease, scleroderma, inflammatory bowel cancer (including Crohn disease and ulcerative colitis), autoimmune hepatitis, toxic epidermal necrolysis or Stevens-Johnson syndrome.
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 |
|---|---|---|
| Amivantamab+ systemic/ intrathecal PemetrexedAmivantamab dosing regimen: once weekly in the first month, 350 mg each time; no dosing is required in weeks 5 and 6. Starting from week 7, 700 mg each time once every 3 weeks. Systemic pemetrexed dosing regimen: day 1 of week 1, week 4, week 7 and once every 3 weeks thereafter, 500 mg/m2. Intrathecal injection shall be performed by personnel qualified to perform intrathecal injection (personnel of the Department of Radiation Oncology of our hospital holding standardized residency training certificates). | Drug | Treatment group |
Primary outcome
Number of Participants with Treatment-Related Adverse Events as Assessed by CTCAE v5.0"
Time frame: 2 year
The primary safety analysis will be conducted in subjects who develop toxicities (as defined according to CTCAE criteria). Safety will be evaluated using CTCAE version 5.0 through reported adverse events. The relationship between adverse events and the drug, time of onset, duration of the event, resolution of the event and any concomitant medication will be recorded. Adverse events (AEs) will be analyzed, including but not limited to all AEs, serious adverse events (SAEs), fatal AEs and laboratory changes.
8 secondary outcomes
ORR
Time frame: 2 year
DCR
Time frame: 2 year
Overall survival
Time frame: 2 year
Progression-Free Survival
Time frame: 2 year
3-month OS rate
Time frame: 3 months
6-month OS rate
Time frame: 6 months
9-month OS rate
Time frame: 9 months
1-year OS rate
Time frame: 1 year
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 4 Aug 2026.
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Amivantamab+ systemic/ intrathecal Pemetrexed in people with Leptomeningeal Metastasis From Lung Cancer, run by Second Affiliated Hospital, Zhejiang University, School of Medicine at 1 site in China.
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 15 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: looking for participants now, as of the sponsor's last update on 4 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 Bicheng Zhang (86+15067126742, bicheng_zhang@zju.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants with Treatment-Related Adverse Events as Assessed by CTCAE v5.0" (time frame: 2 year). 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 4 Aug 2026.