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Not yet recruitingNCT06766591Updated Jan 9, 2025

Ivonescimab Combined With Chemotherapy for the Treatment of Leptomeningeal Metastases Failed to EGFR-TKIs

An interventional study of Ivonescimab combined with chemotherapy in NSCLC, Chemotherapy and Leptomeningeal Metastases, sponsored by Jiangsu Province Nanjing Brain Hospital. Not yet recruiting. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2025-01-09.

Sponsored by Jiangsu Province Nanjing Brain Hospital · Not applicable, Interventional, and Treatment

From the registry’s dates

  • Primary completion was expected by Oct 2025, 11 months ago, but the record still lists the study as not yet recruiting.
Phase
Not applicable
Study type
Interventional
Enrollment
36
Allocation
Not applicable
Ages
18 Years to 75 Years
Sex
All
01

Study 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).

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

02

Conditions studied

  • NSCLC
  • Chemotherapy
  • Leptomeningeal Metastases
  • EGFR-TKI
  • AK112

Keywords

  • Ivonescimab
  • NSCLC
  • leptomeningeal metastases
  • EGFR-TKI
  • VEGF
  • PD-1/VEGF bispecific antibody
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In context

Neoplasm Metastasis

3,517 studies on the registry are indexed under Neoplasm Metastasis; 885 are open to participants now.

This study's planned enrollment of 36 is below the median of 54 across 2,767 interventional studies indexed under Neoplasm Metastasis.

Browse Neoplasm Metastasis studies →

Lead sponsor

Jiangsu Province Nanjing Brain Hospital is the lead sponsor of 22 studies on the registry; 17 are open to participants now.

Counted across the registry records on this site, refreshed daily.

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Who can participate

Ages eligible
18 Years to 75 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • 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

Exclusion criteria

Exclusion Criteria:

  • 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
  • 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
05

Study design

Phase
Not applicable
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
36 participants (estimated)

Study arms

  • Experimental
    Ivonescimab combined with chemotherapy

    Drug: Ivonescimab combined with chemotherapy

Interventions

  • DrugIvonescimab combined with chemotherapy

    Ivonescimab combined with chemotherapy. The specific chemotherapy regimen is based on the real world.

06

What researchers measure

Primary outcomes

  1. intracranial progression free survival(iPFS)

    Treatment initiation to intracranial progression/death/deadline for last follow-up

    Time frame: From enrollment to the end of treatment at 12 months

Secondary outcomes

  1. PFS

    Treatment start to PD/death/deadline for last follow-up

    Time frame: From enrollment to the end of treatment at 12 months

  2. OS

    The time from randomization to death (for any reason)

    Time frame: From enrollment to the end of treatment at 18 months

  3. 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

    Time frame: From enrollment to the end of treatment at 12 months

07

Study locations

No study locations are listed for this record.

08

References and documents

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 39661367 ↗
  • Liu 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 39661345 ↗
  • Fang 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 39661384 ↗
  • Frentzas 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 38642937 ↗
  • Dhillon S. Ivonescimab: First Approval. Drugs. 2024 Sep;84(9):1135-1142. doi: 10.1007/s40265-024-02073-w. Epub 2024 Jul 29. PubMed 39073550 ↗
  • HARMONi-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 38820549 ↗
  • Wang 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 37879536 ↗
  • Voron 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 ↗

Individual participant data

Plan to share: No

09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jan 9, 2025, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
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Registry details

Key details

Study ID
NCT06766591
Lead sponsor
Jiangsu Province Nanjing Brain Hospital
Collaborators
Henan Cancer Hospital, Three Gorges Hospital of Chongqing University
Responsible party
Sponsor
First posted
Jan 9, 2025
Start date
Jan 1, 2025 (estimated)
Primary completion
Oct 31, 2025 (estimated)
Completion
Oct 31, 2025 (estimated)
Last update
Jan 9, 2025

Study contacts

Cun shen Fang, Dr
Contact
fang1984@aliyun.com
13404163638

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is not yet recruiting, as verified in Jan 2025. You cannot join it, but the record below documents what was studied.

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