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

NCT06766591 | Not Yet Recruiting DMC

• 1 other identifier: 2024-KY110-01
• Study Type: interventional
• Target: 36
• Locations: 0 countries
• Sites: N/A

Brief 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

Conditions

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

Keywords

Ivonescimab; NSCLC; leptomeningeal metastases; EGFR-TKI; VEGF; PD-1/VEGF bispecific antibody

Outcome Measures

Primary Outcomes (1)

• intracranial progression free survival(iPFS)

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

  From enrollment to the end of treatment at 12 months

Secondary Outcomes (3)

• PFS

  From enrollment to the end of treatment at 12 months

• OS

  From enrollment to the end of treatment at 18 months

• iDoR

  From enrollment to the end of treatment at 12 months

Study Arms (1)

Ivonescimab combined with chemotherapy

EXPERIMENTAL

Drug: Ivonescimab combined with chemotherapy

Interventions

Ivonescimab combined with chemotherapy DRUG

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

Ivonescimab combined with chemotherapy

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Jiangsu Province Nanjing Brain Hospital: lead
• Henan Cancer Hospital: collaborator
• Three Gorges Hospital of Chongqing University: collaborator

Related Publications (8)

• 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.

  PMID: 39661367 RESULT

• 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.

  PMID: 39661345 RESULT

• 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.

  PMID: 39661384 RESULT

• 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.

  PMID: 38642937 RESULT

• Dhillon S. Ivonescimab: First Approval. Drugs. 2024 Sep;84(9):1135-1142. doi: 10.1007/s40265-024-02073-w. Epub 2024 Jul 29.

  PMID: 39073550 RESULT

• 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.

  PMID: 38820549 RESULT

• 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.

  PMID: 37879536 RESULT

• 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.

  PMID: 25601652 RESULT

MeSH Terms

Conditions

Meningeal Carcinomatosis

Interventions

Drug Therapy

Condition Hierarchy (Ancestors)

Meningeal Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Therapeutics

Central Study Contacts

Cun shen Fang, Dr

CONTACT

13404163638; fang1984@aliyun.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 22, 2024
• First Posted: January 9, 2025
• Study Start: January 1, 2025
• Primary Completion: October 31, 2025
• Study Completion: October 31, 2025
• Last Updated: January 9, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share