Zorifertinib Plus Intra-Ommaya CSF Chemotherapy for Leptomeningeal Progression in NSCLC After Third-Generation EGFR-TKI

NCT07551414 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: NCC6051
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

Brief Summary

A Prospective Study of Zorifertinib Combined with Intra-Ommaya Reservoir Cerebrospinal Fluid Chemotherapy for Leptomeningeal Progression in NSCLC Patients After Third-Generation EGFR-TKI Therapy

Conditions

Leptomeningeal Metastasis; EGFR-TKI Sensitizing Mutation; Zorifertinib; NSCLC (Non-small Cell Lung Carcinoma)

Keywords

Leptomeningeal Metastasis; NSCLC; zorifertinib; EGFR-TKI Sensitizing Mutation

Outcome Measures

Primary Outcomes (1)

• Response Assessment in Neuro - Oncology Leptomeningeal Metastases (RANO - LM) criteria

  RANO-LM uses a categorical classification (no single numeric score range) to define disease status: Complete Response (CR): All LM-related lesions disappear, no increase in ventricular size. Partial Response (PR): All measurable LM nodules shrink by ≥50% (sum of perpendicular diameters), no increase in ventricular size. Stable Disease (SD): Neither PR nor Progressive Disease (PD) criteria are met. Progressive Disease (PD): Any of the following: 1. New measurable LM nodule(s); 2. ≥50% increase in the product of perpendicular diameters of any measurable nodule (≥25% if the largest diameter is \<10mm); 3. ≥25% increase in Evan's index (marker of hydrocephalus progression); 4. New linear meningeal enhancement (excluding post-lumbar puncture changes).

  Until the end of the study (up to 3 years)

Secondary Outcomes (1)

• Overall Survival (OS)

  Until the end of the study (up to 3 years)

Study Arms (1)

Zorifertinib Plus Intra-Ommaya CSF Chemotherapy

EXPERIMENTAL

Zorifertinib Plus Intra-Ommaya CSF Chemotherapy for Leptomeningeal Progression in NSCLC After Third-Generation EGFR-TKI Therapy

Drug: Zorifertinib Plus Intra-Ommaya CSF Chemotherapy

Interventions

Zorifertinib Plus Intra-Ommaya CSF Chemotherapy DRUG

Zorifertinib Plus Intra-Ommaya CSF Chemotherapy for Leptomeningeal Progression in NSCLC After Third-Generation EGFR-TKI Therapy

Zorifertinib Plus Intra-Ommaya CSF 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:

• \. Have fully understood the study and voluntarily signed the Informed Consent Form (ICF).
• \. Subjects must be 18-75 years old before signing the Informed Consent Form (ICF).
• \. During the screening phase, subjects must be diagnosed with non-small cell lung cancer (NSCLC) and test positive for EGFR-sensitive mutations (L858R and/or Exon 19Del).
• \. Subjects who developed leptomeningeal progression after treatment with third-generation EGFR-TKIs and have no extracranial progression. The original third-generation EGFR-TKIs may be continued at the original dose or reduced dose.
• \. Subjects diagnosed with leptomeningeal metastasis must have positive cerebrospinal fluid (CSF) cytology results. Subjects with negative CSF cytology but clinically diagnosed leptomeningeal metastasis based on symptoms, brain or spinal MRI imaging are also eligible for enrollment.
• \. Subjects with both leptomeningeal progression and brain parenchymal progression are allowed to enroll.
• \. Have undergone Ommaya reservoir implantation, with confirmation of no surgery-related complications and normal function of the Ommaya reservoir.
• \. If accompanied by neurological symptoms, the following conditions must be met: able to take oral medication and swallow drugs; no need to increase hormone dosage to control central nervous system symptoms for at least 1 week prior to study treatment (i.e., symptom stability).
• \. All anti-tumor therapy-related toxicities must have recovered to ≤ Grade 1 per CTCAE 5.0 criteria prior to starting study treatment (neurotoxicity related to platinum-based therapy may recover to ≤ Grade 2 per CTCAE 5.0 criteria); alopecia of any grade is allowed for enrollment.
• \. Screening period test results must meet the following criteria:
• Neutrophil count ≥ 1.5 × 10⁹/L
• Platelet count ≥ 100 × 10⁹/L
• Hemoglobin ≥ 90 g/L
• Serum creatinine ≤ 1.5 × ULN, or creatinine clearance (calculated via Cockcroft-Gault formula) ≥ 50 mL/min
• Total serum bilirubin ≤ 1.5 × ULN (≤ 3 × ULN allowed for patients with Gilbert syndrome or liver metastasis)

You may not qualify if:

• \. Subjects with a history of cranial or spinal radiotherapy within 6 months prior to study drug administration are ineligible for enrollment. Radiotherapy for bone metastases within 3 months prior to study drug administration is also not permitted.
• \. Subjects who have undergone major surgical procedures (e.g., intrathoracic, intra-abdominal, or pelvic surgery) within 4 weeks prior to the first dose of study treatment, or who have not yet recovered from side effects related to such surgeries, are ineligible for enrollment.
• \. Subjects with any other currently active malignant tumor besides NSCLC are excluded.
• \. Subjects with clinically significant, uncontrolled cardiac disease and/or cardiac events occurring within the past 6 months, such as:
• Myocardial infarction within 6 months prior to screening;
• Documented history of heart failure (NYHA Class III-IV);
• Uncontrolled hypertension: systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥100 mmHg, regardless of antihypertensive medication use (adjustment of antihypertensive drugs prior to screening is permitted);
• Drug-refractory arrhythmias;
• Screening QTcF \>470 ms;
• Left ventricular ejection fraction (LVEF) \<50%. 5. Subjects with gastrointestinal diseases or severe impairment of gastrointestinal function that may significantly affect drug absorption (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, or malabsorption syndrome).
• \. Subjects unable to discontinue the following medications within 1 week prior to study drug administration and during the study period:
• Strong inducers or strong inhibitors of CYP3A4;
• Drugs that may prolong the QT interval or induce torsades de pointes. 7. Subjects with prior or current HIV infection are excluded. HCV antibody-positive subjects may be enrolled if HCV RNA is undetectable (with the lower limit of detection defined per each center's standards) and there is no concurrent hepatitis B virus (HBV) infection. HBV-infected subjects may be enrolled if they meet the following conditions:
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• For active hepatitis B patients: at least 6 weeks of antiviral therapy prior to starting study treatment, with HBV DNA \<100 IU/mL and ALT/AST levels \<ULN;

Sponsors & Collaborators

• Cancer Institute and Hospital, Chinese Academy of Medical Sciences: lead
• Alpha Biopharma (Jiangsu) Co., Ltd.: collaborator

Study Sites (1)

National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College

Beijing, China

Location

Related Publications (8)

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  PMID: 38377785 BACKGROUND

• Fan C, Zhao Q, Li L, Shen W, Du Y, Teng C, Gao F, Song X, Jiang Q, Huang D, Jin Y, Lv Y, Wei L, Shi T, Zhao X, Gao N, Jiang Z, Xin T. Efficacy and Safety of Intrathecal Pemetrexed Combined With Dexamethasone for Treating Tyrosine Kinase Inhibitor-Failed Leptomeningeal Metastases From EGFR-Mutant NSCLC-a Prospective, Open-Label, Single-Arm Phase 1/2 Clinical Trial (Unique Identifier: ChiCTR1800016615). J Thorac Oncol. 2021 Aug;16(8):1359-1368. doi: 10.1016/j.jtho.2021.04.018. Epub 2021 May 11.

  PMID: 33989780 BACKGROUND

• Montes de Oca Delgado M, Cacho Diaz B, Santos Zambrano J, Guerrero Juarez V, Lopez Martinez MS, Castro Martinez E, Avendano Mendez-Padilla J, Mejia Perez S, Reyes Moreno I, Gutierrez Aceves A, Gonzalez Aguilar A. The Comparative Treatment of Intraventricular Chemotherapy by Ommaya Reservoir vs. Lumbar Puncture in Patients With Leptomeningeal Carcinomatosis. Front Oncol. 2018 Nov 20;8:509. doi: 10.3389/fonc.2018.00509. eCollection 2018.

  PMID: 30524956 BACKGROUND

• Abbott NJ, Ronnback L, Hansson E. Astrocyte-endothelial interactions at the blood-brain barrier. Nat Rev Neurosci. 2006 Jan;7(1):41-53. doi: 10.1038/nrn1824.

  PMID: 16371949 BACKGROUND

• Abbott NJ, Patabendige AA, Dolman DE, Yusof SR, Begley DJ. Structure and function of the blood-brain barrier. Neurobiol Dis. 2010 Jan;37(1):13-25. doi: 10.1016/j.nbd.2009.07.030. Epub 2009 Aug 5.

  PMID: 19664713 BACKGROUND

• Wilcox JA, Jeng MY, Tischfield S, Sui JSY, Nemirovsky D, Heller G, Choudhury NJ, Ross JS, Rudin CM, Riely GJ, Kris MG, Donoghue M, Boire AA, Yu HA. Identifying the genomic landscape of EGFR-mutant lung cancers with central nervous system metastases. Ann Oncol. 2025 Oct;36(10):1142-1153. doi: 10.1016/j.annonc.2025.06.001. Epub 2025 Jun 16.

  PMID: 40532851 BACKGROUND

• Jia C, Xu Q, Zhao L, Kong F, Jia Y. Therapeutic role of EGFR - Tyrosine kinase inhibitors in non-small cell lung cancer with leptomeningeal metastasis. Transl Oncol. 2024 Jan;39:101832. doi: 10.1016/j.tranon.2023.101832. Epub 2023 Nov 25.

  PMID: 38006761 BACKGROUND

• Wang Y, Yang X, Li NJ, Xue JX. Leptomeningeal metastases in non-small cell lung cancer: Diagnosis and treatment. Lung Cancer. 2022 Dec;174:1-13. doi: 10.1016/j.lungcan.2022.09.013. Epub 2022 Oct 1.

  PMID: 36206679 BACKGROUND

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Meningeal Carcinomatosis

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Meningeal Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Nervous System Diseases

Study Officials

• Wan Jinghai

  Chinese Academy of Medical Sciences

  STUDY CHAIR

Central Study Contacts

Wan Jinghai, Professor

CONTACT

8610-87788495; wanjinghai@sina.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Physician/Professor

Model Details: This study is a single-center, single-arm, open-label, prospective clinical study.

Study Record Dates

• First Submitted: April 17, 2026
• First Posted: April 24, 2026
• Study Start (Estimated): May 30, 2026
• Primary Completion (Estimated): May 30, 2027
• Study Completion (Estimated): May 30, 2028
• Last Updated: April 24, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Beginning 1 year after publication with no end date
• Access Criteria: Access Criteria Individual participant data (IPD) and supporting documents for this trial will be shared with qualified researchers upon reasonable request, pending independent review committee approval and a signed Data Sharing Agreement. * Who: Qualified researchers conducting legitimate scientific research (e.g., academic/healthcare institutions) with proper ethical approvals for their proposals. * What: De-identified IPD (demographics, baseline traits, efficacy endpoints like LM-PFS/OS/LM-ORR, safety data) and core documents (protocol, SAP, ICF template). Extra materials (e.g., imaging guidelines) may be provided upon request. * How: Submit requests to the sponsor's data sharing contact (cancergcp@163.com). Access requires formal proposal review to align with trial's ethical/legal/privacy rules and completion of the Data Sharing Agreement.

Locations

CN (1)