NSCLC (Non-small Cell Lung Carcinoma)Phase 2NCT07551414
Zorifertinib Plus Intra-Ommaya CSF Chemotherapy for Leptomeningeal Progression in NSCLC After Third-Generation EGFR-TKI
A Phase 2 study testing Zorifertinib Plus Intra-Ommaya CSF Chemotherapy in people with NSCLC (Non-small Cell Lung Carcinoma) and Leptomeningeal Metastasis, run by Cancer Institute and Hospital, Chinese Academy of Medical Sciences at 1 site in China.
Trial 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 Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- NSCLC (Non-small Cell Lung Carcinoma), Leptomeningeal Metastasis, EGFR-TKI Sensitizing Mutation
- What is being tested?
- Zorifertinib Plus Intra-Ommaya CSF Chemotherapy
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 38 participants
- Where
- 1 siteChina
- Study dates
- 30 May 2026to 30 May 2028
- Phase
- Phase 2
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
- 1. Have fully understood the study and voluntarily signed the Informed Consent Form (ICF).
- 2. Subjects must be 18-75 years old before signing the Informed Consent Form (ICF).
- 3. 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).
- 4. 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.
- 5. 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.
- 6. Subjects with both leptomeningeal progression and brain parenchymal progression are allowed to enroll.
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- 7. Have undergone Ommaya reservoir implantation, with confirmation of no surgery-related complications and normal function of the Ommaya reservoir.
- 8. 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).
- 9. 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.
- 10. 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)
- Aspartate aminotransferase (AST) ≤ 2.5 × ULN (≤ 5 × ULN allowed for patients with liver metastasis)
- Alanine aminotransferase (ALT) ≤ 2.5 × ULN (≤ 5 × ULN allowed for patients with liver metastasis) 11. Estimated survival duration ≥ 3 months. 12. Karnofsky Performance Status (KPS) score ≥ 60.
Who cannot join
- 1. 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.
- 2. 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.
- 3. Subjects with any other currently active malignant tumor besides NSCLC are excluded.
- 4. 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);
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- 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).
- 6. 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;
- For resolved or chronic hepatitis B patients: at least 2 weeks of prophylactic antiviral therapy prior to starting study treatment, with HBV DNA below 100 IU/mL (e.g., inactive carriers) and ALT/AST levels <ULN.
- 8. Pregnant or breastfeeding women; women of childbearing potential must agree to use highly effective contraception during the treatment period and for 3 months after the last dose; fertile men must also use highly effective contraception during the treatment period and for 6 months after the last dose.
- 9. Subjects with a prior history of interstitial lung disease, including clinically significant radiation pneumonitis (e.g., affecting daily life or requiring therapeutic intervention).
- 10. Subjects who have previously received zorifertinib or its active pharmaceutical ingredient.
- 11. Known hypersensitivity to zorifertinib's active ingredients, excipients, or drugs with similar chemical structures or classes.
- 12. Subjects with other comorbid diseases or factors that, in the investigator's judgment, would pose excessive risk to the subject upon participation in the clinical trial.
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
National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
Beijing
National Cancer Center/Cancer Hospital, 8610-87788495, cancergcp@163.com
About this study
Official title: A Prospective Study of Zorifertinib Plus Intra-Ommaya CSF Chemotherapy for Leptomeningeal Progression in NSCLC After Third-Generation EGFR-TKI Therapy
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
Read the detailed description
This study is a prospective clinical trial evaluating the preliminary efficacy and safety of zorifertinib combined with intra-Ommaya reservoir cerebrospinal fluid (CSF) chemotherapy in patients with non-small cell lung cancer (NSCLC) who develop leptomeningeal progression after prior third-generation EGFR-TKI therapy.
The study will enroll patients with advanced NSCLC harboring EGFR-sensitive mutations (L858R and/or Exon 19Del) who experience leptomeningeal progression without concurrent extracranial disease progression following third-generation EGFR-TKI treatment. A total of 38 participants are planned for enrollment. Upon enrollment, participants will receive oral zorifertinib plus pemetrexed administered via the Ommaya reservoir for CSF chemotherapy, alongside standard clinical care. Treatment will continue until disease progression, occurrence of intolerable toxicity, initiation of new anti-tumor therapy, withdrawal of informed consent, loss to follow-up, death, or any other circumstance deemed by the investigator as requiring treatment discontinuation-whichever occurs first.
- Conditions
- NSCLC (Non-small Cell Lung Carcinoma), Leptomeningeal Metastasis, EGFR-TKI Sensitizing Mutation, Zorifertinib
- Being tested
- Zorifertinib Plus Intra-Ommaya CSF Chemotherapy
- Keywords
- Leptomeningeal Metastasis, NSCLC, zorifertinib, EGFR-TKI Sensitizing Mutation
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Meningeal Carcinomatosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Zorifertinib Plus Intra-Ommaya CSF ChemotherapyDrug
Zorifertinib Plus Intra-Ommaya CSF Chemotherapy for Leptomeningeal Progression in NSCLC After Third-Generation EGFR-TKI Therapy
| Study group | Role | What they receive |
|---|---|---|
| Zorifertinib Plus Intra-Ommaya CSF Chemotherapy | Experimental | Zorifertinib Plus Intra-Ommaya CSF Chemotherapy for Leptomeningeal Progression in NSCLC After Third-Generation EGFR-TKI Therapy Receives: Drug: Zorifertinib Plus Intra-Ommaya CSF Chemotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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:
- New measurable LM nodule(s);
- ≥50% increase in the product of perpendicular diameters of any measurable nodule (≥25% if the largest diameter is <10mm);
- ≥25% increase in Evan's index (marker of hydrocephalus progression);
- New linear meningeal enhancement (excluding post-lumbar puncture changes).
Measured: Until the end of the study (up to 3 years)
Secondary outcomes (1)
Overall Survival (OS)
Overall Survival (OS)
Measured: Until the end of the study (up to 3 years)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Apr 2026
- Study start30 May 2026 (estimated)
- Primary completion30 May 2027 (estimated)
- Study completion30 May 2028 (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 NSCLC (Non-small Cell Lung Carcinoma)Studies 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- This study is a single-center, single-arm, open-label, prospective clinical study.
- Masking
- None (open label)
- Enrolment
- 38 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Cancer Institute and Hospital, Chinese Academy of Medical Sciences
- Sponsor type
- University, hospital or other
- Collaborators
- Alpha Biopharma (Jiangsu) Co., Ltd.
- Responsible party
- Principal investigator, Jinghai Wan, Cancer Institute and Hospital, Chinese Academy of Medical Sciences
- Investigators
- Wan Jinghai, Study chair, Chinese Academy of Medical Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07551414
- Sponsor's protocol ID
- NCC6051
- Status last verified
- Apr 2026
- First submitted
- 17 Apr 2026
- Last updated
- 24 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: all IPD collected throughout the trial
Publications
Fan C, Jiang Z, Teng C, Song X, Li L, Shen W, Jiang Q, Huang D, Lv Y, Du L, Wang G, Hu Y, Man S, Zhang Z, Gao N, Wang F, Shi T, Xin T. Efficacy and safety of intrathecal pemetrexed for TKI-failed leptomeningeal metastases from EGFR+ NSCLC: an expanded, single-arm, phase II clinical trial. ESMO Open. 2024 Apr;9(4):102384. doi: 10.1016/j.esmoop.2024.102384. Epub 2024 Feb 19.
PubMed 38377785Fan 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.
PubMed 33989780Montes 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.
PubMed 30524956Abbott 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.
PubMed 16371949Abbott 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.
PubMed 19664713Wilcox 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.
PubMed 40532851Jia 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.
PubMed 38006761Wang 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.
PubMed 36206679