BioTTT001 injection for meningeal metastasis from recurrent non‑small cell lung cancer

Phase Ib/II Clinical Study to Evaluate the Safety, Tolerability, Biodistribution Characteristics and Preliminary Efficacy of BioTTT001 in the Treatment of Patients With Recurrent/Progressive Non-small Cell Lung Cancer

This trial will test whether injecting BioTTT001, an oncolytic adenovirus carrying nsIL12, into the cerebrospinal fluid helps people with recurrent or progressive non‑small cell lung cancer that has spread to the meninges.

Quick facts

• Phase: PHASE1; PHASE2
• Study type: Interventional
• Enrollment: 42 (estimated)
• Ages: 18 Years to 70 Years
• Sex: All
• Sponsor: Henan Cancer Hospital (other gov)
• Drugs / interventions: chemotherapy, immunotherapy, methotrexate, cyclophosphamide
• Locations: 1 site (Zhengzhou, Henan)
• Trial ID: NCT07264569 on ClinicalTrials.gov

What this trial studies

This is a single‑arm, open‑label Phase Ib/II trial with a dose‑escalation stage followed by a dose‑expansion stage to study BioTTT001 delivered into the cerebrospinal fluid via an Ommaya reservoir. The dose escalation defines three cohorts (1.0×10^9, 5.0×10^9, and 1.0×10^10 viral particles) to identify tolerable doses, then expands the selected dose in Phase II. Key outcomes include safety, tolerability, biodistribution of the virus in CSF and CNS tissues, and signals of preliminary anti‑tumor activity. Eligible patients have recurrent or progressive NSCLC with tumor cells in CSF or MRI evidence of meningeal metastasis and adequate organ function.

Who should consider this trial

Good fit: Adults aged 18–70 with recurrent or progressive non‑small cell lung cancer and CSF‑positive tumor cells or MRI‑diagnosed meningeal metastasis, ECOG/PS ≤3, suitable for Ommaya reservoir placement, expected survival ≥3 months, and adequate organ and coagulation function are the intended participants.

Not a fit: Patients who are not candidates for Ommaya reservoir placement, have very poor performance status or life expectancy under three months, significant uncontrolled organ dysfunction or bleeding risk, or other conditions excluded by protocol are unlikely to benefit from this trial.

Why it matters

Potential benefit: If successful, this approach could slow or control leptomeningeal tumor growth and improve neurologic symptoms by delivering a targeted oncolytic virus directly into the CSF.

How similar studies have performed: This is largely experimental: oncolytic adenoviruses and IL‑12‑armed vectors have shown promising preclinical and very early‑phase clinical signals in some cancers, but intrathecal use for meningeal metastasis has limited clinical data and no established proof of benefit.

Eligibility criteria

Inclusion Criteria:

1. Age between 18 and 70 years old (including boundary values);
2. Patients diagnosed with NSCLC through pathological histology, who have experienced recurrence or progression after standard treatment, and have tumor cells found in cerebrospinal fluid or MRI diagnosis of leptomeningeal metastasis;
3. Performance Status (PS) score ≤ 3 points;
4. Suitable for Ommaya reservoir placement as determined by the investigator, and meet the conditions for drug administration;
5. Expected survival ≥ 3 months;
6. Good organ function, defined as follows:

   1. Blood routine (not having received blood transfusion or other treatments within 14 days): Absolute neutrophil count ≥ 1.5 × 10\^9/L, platelet count ≥ 100 × 10\^9/L, hemoglobin ≥ 90 g/L, white blood cell count ≥ 3.0 × 10\^9/L;
   2. Coagulation function: Activated Partial Thromboplastin Time (APTT) ≤ 1.5 times the upper limit of normal (ULN), International Normalized Ratio (INR) ≤ 1.5 times ULN;
   3. Liver function: Total bilirubin (TBIL) ≤ 1.5 times ULN, Gilbert's syndrome participants should be ≤ 3 times ULN, Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) ≤ 3 times ULN (if there is liver metastasis, ALT or AST ≤ 5 times ULN);
   4. Renal function: Serum creatinine ≤ 1.5 times ULN, or creatinine clearance rate ≥ 50 mL/min (Cockcroft-Gault formula calculation see Appendix 3);
7. Voluntarily participate and sign the informed consent form after being explained the study content before the start of the relevant procedures;
8. For participants and partners with reproductive capacity and sexual activity, must agree to use medically approved effective contraception methods during treatment and for 6 months after the last dose, such as double-barrier contraception, and men agree not to donate sperm;
9. For women with reproductive capacity, the blood pregnancy test result within 7 days before the first dose must be negative, and willing to undergo additional pregnancy tests during the study. Reproductive capacity refers to women who have not undergone surgical sterilization (i.e., bilateral tubal ligation, bilateral oophorectomy, or total hysterectomy) or are not postmenopausal; Menopause is defined as amenorrhea ≥ 12 months in women over 45 years old, excluding other causes of amenorrhea. Additionally, for women under 50 years old, serum Follicle-Stimulating Hormone (FSH) levels must be in the postmenopausal range to confirm menopause;
10. Good compliance, willing and able to follow all study procedures and cooperate with observation and follow-up.
11. If patients have previously received tyrosine kinase inhibitors (TKIs) treatment for more than two weeks and have only brain progression, they should continue the TKIs treatment during the enrollment period and cannot arbitrarily switch to other TKIs.

Exclusion Criteria:

1. Patients who have received systemic antitumor therapy within two weeks, including intravenous chemotherapy, intrathecal chemotherapy, or whole-brain radiotherapy (excluding immunotherapy);
2. immunotherapy administered within 6 weeks prior to the first dose;
3. traditional Chinese medicine with antitumor indications administered within 2 weeks prior to the first dose;
4. patients with uncontrolled epilepsy;
5. those who received any other investigational drug within 4 weeks prior to the first dose;
6. major organ surgeries (excluding biopsy) or significant trauma within 4 weeks prior to the first dose, or those requiring elective surgery during the study;
7. patients with prior history of cell therapy, gene therapy, or oncolytic virus therapy;
8. individuals with known or suspected allergies to active ingredients, excipients, or contrast agents in the study drug or imaging contrast agents;
9. patients with organ transplant history or planned organ transplant during the study;
10. active infections requiring systemic intravenous treatment or uncontrolled infections, or unexplained fever\>38.5℃ occurring during screening or before the first dose;
11. patients with severe coagulation disorders or evidence of significant bleeding risk; history of gastrointestinal bleeding; any other CTCAE 2-level or higher bleeding events within 6 months;
12. participants who received immunosuppressants (e.g., azathioprine, cyclophosphamide, methotrexate, thalidomide) within 14 days prior to the first dose;
13. patients whose adverse reactions from previous antitumor therapy have not resolved to a CTCAE 5.0 grade ≤1 (excluding non-safety-related toxicities like alopecia as determined by investigators);
14. patients with immunodeficiency history, including HIV antibody-positive status;
15. Active hepatitis B (HBsAg-positive with HBV-DNA\> 500 IU/mL or laboratory test lower limit \[only when the laboratory test lower limit exceeds 500 IU/mL\]); Active hepatitis C (HCV antibody positive with HCV-RNA\> laboratory test lower limit); Positive Treponema pallidum antibody;
16. Hypertension poorly controlled by investigators (uncontrolled arterial hypertension despite standardized treatment: systolic blood pressure ≥160mmHg and/or diastolic blood pressure ≥100 mmHg);
17. History of severe cardiovascular disease: such as clinically managed ventricular arrhythmias; QTc interval\> 480 ms; Acute coronary syndrome, congestive heart failure, stroke, or other Grade III or higher cardiovascular events within 6 months prior to first dose; New York Heart Association (NYHA) class II or left ventricular ejection fraction (LVEF) \<50%;
18. Concurrent presence of other uncured malignancies within 3 years (excluding clinically curable precancerous conditions like cervical carcinoma in situ and basal cell carcinoma);
19. Active or recurrent autoimmune diseases (including but not limited to systemic lupus erythematosus, rheumatoid arthritis, vasculitis, etc.) except clinically stable autoimmune thyroiditis;
20. Vaccination history within 4 weeks prior to first dose (live attenuated vaccines/recombinant vaccines) or within 2 weeks prior to first dose (inactivated vaccines);
21. Previous immunotherapy with irAE grade ≥3;
22. Patients with intracranial brainstem metastases or rapidly progressing diffuse cerebral parenchymal metastases;
23. those showing tumor enhancement margins invading ventricular walls on cranial MRI or postoperative ventricular communication;
24. history of encephalitis, multiple sclerosis, or other CNS infections;
25. cerebral herniation syndrome;
26. confirmed alcohol/drug dependence;
27. psychiatric disorders or poor compliance;
28. Pregnant or lactating women;
29. Researchers believe that due to other serious systemic diseases or other reasons, the subjects are not suitable to participate in this clinical study.

Where this trial is running

Zhengzhou, Henan

• Phase Ib/II Clinical Study to Evaluate the Safety, Tolerability, Biodistribution Characteristics and Preliminary Efficacy of Recombinant Human nsIL12 Oncolytic Adenovirus Injection (BioTTT001) in the Treatment of Patients With Recurrent/Progressive Non-s — Zhengzhou, Henan, China (RECRUITING)

Study contacts

• Study coordinator: Henan Province Cancer Hospital Ethics Committee Henan Province Cancer Hospital Ethics Committee

Conditions: Meningeal Metastasis