NSCLCNCT06766591
Ivonescimab Combined With Chemotherapy for the Treatment of Leptomeningeal Metastases Failed to EGFR-TKIs
A study testing Ivonescimab combined with chemotherapy in people with NSCLC and Chemotherapy, run by Jiangsu Province Nanjing Brain Hospital.
Trial summary
Research objective Main purpose Exploring the real-world effectiveness of Ivonescimab combined with chemotherapy for EGFR mutant NSCLC with leptomeningeal metastasis after EGFR-TKIs resistance. Outcome measure: Real world intracranial disease-free survival time (iPFS). Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- NSCLC, Chemotherapy, Leptomeningeal Metastases
- What is being tested?
- Ivonescimab combined with chemotherapy
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- No sites listed yet
- Study dates
- 1 Jan 2025to 31 Oct 2025
- Phase
- Interventional
- 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 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age range: 18-75y
- EGFR mutation NSCLC
- LM was diagnosed through head enhanced MRI or (and) CSF cytology
- EGFR activation mutations were positive
- Patients who have failed to first or second-generation EGFR-TKI treatment，without T790M mutation; or failed to third-generation EGFR-TKI treatment
- Hematological, coagulation, renal and liver function is sufficient
- Women of childbearing age must undergo a pregnancy test and the result must be negative
Who cannot join
- Patients with squamous cell carcinoma, large cell carcinoma, mixed cell lung cancer
- The patient has other driver genes that can be treated with targeted drugs
- Subjects who have previously received immunotherapy with a discontinuation time of less than 3 months
- Received EGFR-TKI treatment within one week prior to the first administration
- Received non-specific immunomodulatory therapy
- Clinical manifestations of neurological failure
Show all 12Show fewer
- Non malignant neurological disorders
- Radiotherapy for the chest and whole brain should be completed within 4 weeks before enrollment
- Tumor surrounded important blood vessels or had obvious necrosis or cavities
- Tumor has invaded important surrounding organs and blood vessels
- History of severe bleeding tendency or coagulation dysfunction
- The risk of developing esophagotracheal fistula or esophageal pleural fistula
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: Ivonescimab Combined With Chemotherapy for EGFR Mutant NSCLC With Leptomeningeal Metastasis After EGFR TKIs Resistance: A Multicenter Observational Study.
Research objective Main purpose Exploring the real-world effectiveness of Ivonescimab combined with chemotherapy for EGFR mutant NSCLC with leptomeningeal metastasis after EGFR-TKIs resistance. Outcome measure: Real world intracranial disease-free survival time (iPFS).
Secondary purpose Federation patterns: describing different treatment modes in the real world; Outcome measures: Combination chemotherapy regimen and duration of chemotherapy.
Read more
Efficacy: Further explore the effectiveness of Ivonescimab combined with chemotherapy for EGFR mutant NSCLC with leptomeningeal metastasis failed with EGFR-TKI treatment; Outcome measures: Objective response rate (LM-ORR), duration of intracranial response (iDoR), overall progression free survival (PFS), overall survival (OS), improvement in neurological function, CSF response rate based on CSF cytology.
Safety: Explore the safety of Ivonescimab combined with chemotherapy for NSCLC patients with leptomeningeal metastases who have failed EGFR-TKI treatment; Outcome measures: incidence of adverse events (TEAEs), laboratory test outliers, and serious adverse events (SAEs).
Research endpoint Primary endpoint
- iPFS (intracranial progression free survival). Secondary endpoint
- Efficacy: leptomeningeal ORR (LM-ORR), intracranial duration of response (iDoR), overall progression free survival (PFS), overall survival (OS), improvement in neurological function, and CSF response rate based on CSF cytology;
- Safety: Determine the incidence and severity of adverse events (AE) and serious adverse events (SAE) according to NCI-CTCAE5.0 standards; Changes in vital signs, laboratory abnormalities, and quality of life scores.
Exploratory endpoint: efficacy related biomarkers
- Conditions
- NSCLC, Chemotherapy, Leptomeningeal Metastases, EGFR-TKI, AK112
- Being tested
- Ivonescimab combined with chemotherapy
- Keywords
- Ivonescimab, NSCLC, leptomeningeal metastases, EGFR-TKI, VEGF, PD-1/VEGF bispecific antibody
- Medical subject headings
- Meningeal Carcinomatosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ivonescimab combined with chemotherapyDrug
Ivonescimab combined with chemotherapy. The specific chemotherapy regimen is based on the real world.
| Study group | Role | What they receive |
|---|---|---|
| Ivonescimab combined with chemotherapy | Experimental | Not described Receives: Drug: Ivonescimab combined with chemotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
intracranial progression free survival(iPFS)
Treatment initiation to intracranial progression/death/deadline for last follow-up
Measured: From enrollment to the end of treatment at 12 months
Secondary outcomes (3)
PFS
Treatment start to PD/death/deadline for last follow-up
Measured: From enrollment to the end of treatment at 12 months
OS
The time from randomization to death (for any reason)
Measured: From enrollment to the end of treatment at 18 months
iDoR
The time from the first assessment of intracranial lesions as CR or PR to the first assessment as PD or death from any cause
Measured: From enrollment to the end of treatment at 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jan 2025
- Study start1 Jan 2025 (estimated)
- Primary completion31 Oct 2025 (estimated)
- Study completion31 Oct 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for NSCLCStudies 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 N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 36 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Jiangsu Province Nanjing Brain Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Henan Cancer Hospital, Three Gorges Hospital of Chongqing University
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06766591
- Sponsor's protocol ID
- 2024-KY110-01
- Status last verified
- Jan 2025
- First submitted
- 22 Dec 2024
- Last updated
- 9 Jan 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Cheng WC, Wang G, Mei Q. Ivonescimab Plus Chemotherapy in Patients With EGFR Variant Non-Small Cell Lung Cancer. JAMA. 2025 Jan 14;333(2):172. doi: 10.1001/jama.2024.23088. No abstract available.
PubMed 39661367Liu Z, Shan D, Han X. Ivonescimab Plus Chemotherapy in Patients With EGFR Variant Non-Small Cell Lung Cancer. JAMA. 2025 Jan 14;333(2):172-173. doi: 10.1001/jama.2024.23091. No abstract available.
PubMed 39661345Fang W, Li W, Zhang L. Ivonescimab Plus Chemotherapy in Patients With EGFR Variant Non-Small Cell Lung Cancer-Reply. JAMA. 2025 Jan 14;333(2):173-174. doi: 10.1001/jama.2024.23094. No abstract available.
PubMed 39661384Frentzas S, Austria Mislang AR, Lemech C, Nagrial A, Underhill C, Wang W, Wang ZM, Li B, Xia Y, Coward JIG. Phase 1a dose escalation study of ivonescimab (AK112/SMT112), an anti-PD-1/VEGF-A bispecific antibody, in patients with advanced solid tumors. J Immunother Cancer. 2024 Apr 19;12(4):e008037. doi: 10.1136/jitc-2023-008037.
PubMed 38642937Dhillon S. Ivonescimab: First Approval. Drugs. 2024 Sep;84(9):1135-1142. doi: 10.1007/s40265-024-02073-w. Epub 2024 Jul 29.
PubMed 39073550HARMONi-A Study Investigators; Fang W, Zhao Y, Luo Y, Yang R, Huang Y, He Z, Zhao H, Li M, Li K, Song Q, Du X, Sun Y, Li W, Xu F, Wang Z, Yang K, Fan Y, Liu B, Zhao H, Hu Y, Jia L, Xu S, Yi T, Lv D, Lan H, Li M, Liang W, Wang Y, Yang H, Jia Y, Chen Y, Lu J, Feng J, Liu C, Zhou M, Zhou J, Liu X, Zhou N, He M, Dong X, Chen H, Chen Y, Su H, Li X, Zhang Z, Yang L, Cheng Y, Chen L, Hou X, Zhang Y, Guo J, Wang Z, Lu H, Wu D, Feng W, Li W, Huang J, Wang Y, Song X, Peng J, Liu L, Guo Y, Li W, Lu D, Hu M, Wang ZM, Li B, Xia M, Zhang L. Ivonescimab Plus Chemotherapy in Non-Small Cell Lung Cancer With EGFR Variant: A Randomized Clinical Trial. JAMA. 2024 Aug 20;332(7):561-570. doi: 10.1001/jama.2024.10613.
PubMed 38820549Wang L, Luo Y, Ren S, Zhang Z, Xiong A, Su C, Zhou J, Yu X, Hu Y, Zhang X, Dong X, Meng S, Wu F, Hou X, Dai Y, Song W, Li B, Wang ZM, Xia Y, Zhou C. A Phase 1b Study of Ivonescimab, a Programmed Cell Death Protein-1 and Vascular Endothelial Growth Factor Bispecific Antibody, as First- or Second-Line Therapy for Advanced or Metastatic Immunotherapy-Naive NSCLC. J Thorac Oncol. 2024 Mar;19(3):465-475. doi: 10.1016/j.jtho.2023.10.014. Epub 2023 Oct 23.
PubMed 37879536Voron T, Colussi O, Marcheteau E, Pernot S, Nizard M, Pointet AL, Latreche S, Bergaya S, Benhamouda N, Tanchot C, Stockmann C, Combe P, Berger A, Zinzindohoue F, Yagita H, Tartour E, Taieb J, Terme M. VEGF-A modulates expression of inhibitory checkpoints on CD8+ T cells in tumors. J Exp Med. 2015 Feb 9;212(2):139-48. doi: 10.1084/jem.20140559. Epub 2015 Jan 19.
PubMed 25601652
Study at a glance
From the registry record, last updated by the sponsor on 9 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ivonescimab Combined With Chemotherapy for EGFR Mutant NSCLC With Leptomeningeal Metastasis After EGFR TKIs Resistance: A Multicenter Observational Study.
- ClinicalTrials.gov ID
- NCT06766591
- Acronym / sponsor ID
- 2024-KY110-01
- Conditions
- NSCLC, Chemotherapy, Leptomeningeal Metastases, EGFR-TKI, AK112
- Keywords
- Ivonescimab, NSCLC, leptomeningeal metastases, EGFR-TKI, VEGF, PD-1/VEGF bispecific antibody
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 36 participants (estimated)
- Lead sponsor
- Jiangsu Province Nanjing Brain HospitalUniversity, hospital or other
- Collaborators
- Henan Cancer Hospital, Three Gorges Hospital of Chongqing University
- Study start
- 1 Jan 2025 (estimated)
- Primary completion
- 31 Oct 2025 (estimated)
- Study completion
- 31 Oct 2025 (estimated)
- First posted
- 9 Jan 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.
Research objective Main purpose Exploring the real-world effectiveness of Ivonescimab combined with chemotherapy for EGFR mutant NSCLC with leptomeningeal metastasis after EGFR-TKIs resistance. Outcome measure: Real world intracranial disease-free survival time (iPFS).
Secondary purpose Federation patterns: describing different treatment modes in the real world; Outcome measures: Combination chemotherapy regimen and duration of chemotherapy.
Efficacy: Further explore the effectiveness of Ivonescimab combined with chemotherapy for EGFR mutant NSCLC with leptomeningeal metastasis failed with EGFR-TKI treatment; Outcome measures: Objective response rate (LM-ORR), duration of intracranial response (iDoR), overall progression free survival (PFS), overall survival (OS), improvement in neurological function, CSF response rate based on CSF cytology.
Safety: Explore the safety of Ivonescimab combined with chemotherapy for NSCLC patients with leptomeningeal metastases who have failed EGFR-TKI treatment; Outcome measures: incidence of adverse events (TEAEs), laboratory test outliers, and serious adverse events (SAEs).
Research endpoint Primary endpoint
- iPFS (intracranial progression free survival). Secondary endpoint
- Efficacy: leptomeningeal ORR (LM-ORR), intracranial duration of response (iDoR), overall progression free survival (PFS), overall survival (OS), improvement in neurological function, and CSF response rate based on CSF cytology;
- Safety: Determine the incidence and severity of adverse events (AE) and serious adverse events (SAE) according to NCI-CTCAE5.0 standards; Changes in vital signs, laboratory abnormalities, and quality of life scores.
Exploratory endpoint: efficacy related biomarkers
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Ivonescimab combined with chemotherapy | Experimental | Drug: Ivonescimab combined with chemotherapy |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Age range: 18-75y
- EGFR mutation NSCLC
- LM was diagnosed through head enhanced MRI or (and) CSF cytology
- EGFR activation mutations were positive
- Patients who have failed to first or second-generation EGFR-TKI treatment，without T790M mutation; or failed to third-generation EGFR-TKI treatment
Key exclusion criteria (12 listed)
- Patients with squamous cell carcinoma, large cell carcinoma, mixed cell lung cancer
- The patient has other driver genes that can be treated with targeted drugs
- Subjects who have previously received immunotherapy with a discontinuation time of less than 3 months
- Received EGFR-TKI treatment within one week prior to the first administration
- Received non-specific immunomodulatory therapy
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 |
|---|---|---|
| Ivonescimab combined with chemotherapyIvonescimab combined with chemotherapy. The specific chemotherapy regimen is based on the real world. | Drug | Ivonescimab combined with chemotherapy |
Primary outcome
intracranial progression free survival(iPFS)
Time frame: From enrollment to the end of treatment at 12 months
Treatment initiation to intracranial progression/death/deadline for last follow-up
3 secondary outcomes
PFS
Time frame: From enrollment to the end of treatment at 12 months
OS
Time frame: From enrollment to the end of treatment at 18 months
iDoR
Time frame: From enrollment to the end of treatment at 12 months
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 9 Jan 2025.
- Results publication: PubMed 39661367Cheng WC, Wang G, Mei Q. Ivonescimab Plus Chemotherapy in Patients With EGFR Variant Non-Small Cell Lung Cancer. JAMA. 2025 Jan 14;333(2):172. doi: 10.1001/jama.2024.23088. No abstract available.
- Results publication: PubMed 39661345Liu Z, Shan D, Han X. Ivonescimab Plus Chemotherapy in Patients With EGFR Variant Non-Small Cell Lung Cancer. JAMA. 2025 Jan 14;333(2):172-173. doi: 10.1001/jama.2024.23091. No abstract available.
- Results publication: PubMed 39661384Fang W, Li W, Zhang L. Ivonescimab Plus Chemotherapy in Patients With EGFR Variant Non-Small Cell Lung Cancer-Reply. JAMA. 2025 Jan 14;333(2):173-174. doi: 10.1001/jama.2024.23094. No abstract available.
- Results publication: PubMed 38642937Frentzas S, Austria Mislang AR, Lemech C, Nagrial A, Underhill C, Wang W, Wang ZM, Li B, Xia Y, Coward JIG. Phase 1a dose escalation study of ivonescimab (AK112/SMT112), an anti-PD-1/VEGF-A bispecific antibody, in patients with advanced solid tumors. J Immunother Cancer. 2024 Apr 19;12(4):e008037. doi: 10.1136/jitc-2023-008037.
- Results publication: PubMed 39073550Dhillon S. Ivonescimab: First Approval. Drugs. 2024 Sep;84(9):1135-1142. doi: 10.1007/s40265-024-02073-w. Epub 2024 Jul 29.
- Results publication: PubMed 38820549HARMONi-A Study Investigators; Fang W, Zhao Y, Luo Y, Yang R, Huang Y, He Z, Zhao H, Li M, Li K, Song Q, Du X, Sun Y, Li W, Xu F, Wang Z, Yang K, Fan Y, Liu B, Zhao H, Hu Y, Jia L, Xu S, Yi T, Lv D, Lan H, Li M, Liang W, Wang Y, Yang H, Jia Y, Chen Y, Lu J, Feng J, Liu C, Zhou M, Zhou J, Liu X, Zhou N, He M, Dong X, Chen H, Chen Y, Su H, Li X, Zhang Z, Yang L, Cheng Y, Chen L, Hou X, Zhang Y, Guo J, Wang Z, Lu H, Wu D, Feng W, Li W, Huang J, Wang Y, Song X, Peng J, Liu L, Guo Y, Li W, Lu D, Hu M, Wang ZM, Li B, Xia M, Zhang L. Ivonescimab Plus Chemotherapy in Non-Small Cell Lung Cancer With EGFR Variant: A Randomized Clinical Trial. JAMA. 2024 Aug 20;332(7):561-570. doi: 10.1001/jama.2024.10613.
- Results publication: PubMed 37879536Wang L, Luo Y, Ren S, Zhang Z, Xiong A, Su C, Zhou J, Yu X, Hu Y, Zhang X, Dong X, Meng S, Wu F, Hou X, Dai Y, Song W, Li B, Wang ZM, Xia Y, Zhou C. A Phase 1b Study of Ivonescimab, a Programmed Cell Death Protein-1 and Vascular Endothelial Growth Factor Bispecific Antibody, as First- or Second-Line Therapy for Advanced or Metastatic Immunotherapy-Naive NSCLC. J Thorac Oncol. 2024 Mar;19(3):465-475. doi: 10.1016/j.jtho.2023.10.014. Epub 2023 Oct 23.
- Results publication: PubMed 25601652Voron T, Colussi O, Marcheteau E, Pernot S, Nizard M, Pointet AL, Latreche S, Bergaya S, Benhamouda N, Tanchot C, Stockmann C, Combe P, Berger A, Zinzindohoue F, Yagita H, Tartour E, Taieb J, Terme M. VEGF-A modulates expression of inhibitory checkpoints on CD8+ T cells in tumors. J Exp Med. 2015 Feb 9;212(2):139-48. doi: 10.1084/jem.20140559. Epub 2015 Jan 19.
- 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 study testing Ivonescimab combined with chemotherapy in people with NSCLC and Chemotherapy, run by Jiangsu Province Nanjing Brain Hospital.
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 7 inclusion and 12 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 9 Jan 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.
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 Cun shen Fang, Dr (13404163638, fang1984@aliyun.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
intracranial progression free survival(iPFS) (time frame: From enrollment to the end of treatment at 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06766591, which also lists 8 linked publications.
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 9 Jan 2025.