NSCLC LM
Conditions
Interventions
Phase Ib dose escalation study:Research product name: Recombinant human nsIL12 oncolytic adenovirus injection Product abbreviation or code: BioTTT001
Phase II dose expansion study:Research product name: Recombinant human nsIL12 oncolytic adenovirus injection Product abbreviation or code: BioTTT001
Sponsors
Henan Cancer Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 70 Years
Inclusion criteria
Inclusion criteria: 1.Age 18 to 70 years(inclusive of the boundary values); 2.Patients who are confirmed by histopathology to be NSCLC, have tumor cells in the cerebrospinal fluid after recurrence/progression after receiving standard treatment, or are diagnosed with meningeal metastasis by MRI; 3.PS score (performance status score) =3 months; 6.Organ function is good, defined as follows: a) Blood routine (no blood transfusion or other treatment has been received within 14 days): absolute neutrophil count >=1.5×10^9/L, platelet count >=100×10^9/L, hemoglobin >=90g/ L, white blood cell count>=3.0×10^9/L; b) Coagulation function: thromboplastin time (APTT) =50 mL/min (see Appendix 3 for Cockcroft-Gault formula calculation); 7.Before the start of the research-related procedures, after explaining the research content, voluntarily participate and be able to sign the informed consent form; 8.Subjects and partners who have childbearing potential and have sexual intercourse must be willing to use medically approved effective contraceptive methods, such as double-barrier contraceptive methods, during treatment and within 6 months after the last dose. Men agree not to donate sperm; 9.Females of childbearing potential must have a negative blood pregnancy test result within 7 days before the first dose and be willing to undergo additional pregnancy tests during the study. Fertility refers to women who have not undergone surgical sterilization (i.e., bilateral fallopian tube ligation, bilateral oophorectomy, or total hysterectomy) or who have not undergone menopause; menopause refers to women over 45 years of age who have not had menstruation for >=12 months, and exclude other Causes of amenorrhea. In addition, serum follicle-stimulating hormone (FSH) levels in women under 50 years of age must be in the postmenopausal range to confirm menopause; 10.Have good compliance, be willing and able to follow all research procedures, and cooperate with observation and follow-up; 11.If the patient has previously received treatment with tyrosine kinase inhibitors(TKIs)for more than two weeks and has only experienced brain metastasis progression,the patient should continue the same TKI treatment during the study period and should not arbitrarily switch to other TKIs.
Exclusion criteria
Exclusion criteria: 1.The patient has received systemic anti-tumor treatment within two weeks, including intravenous chemotherapy, intrathecal chemotherapy or whole-brain radiotherapy (except immunotherapy); 2.Immunotherapy should be administered within 6 weeks before the first dose; 3.Traditional Chinese medicine with anti-tumor indications must be administered within 2 weeks before the first administration; 4.Patients with uncontrollable epilepsy; 5.Have received treatment with any other unmarketed investigational drugs within 4 weeks before the first dose; 6.Have undergone major organ surgery (excluding puncture biopsy) or significant trauma within 4 weeks before the first dose, or need to undergo elective surgery during the study period; 7.Those with a history of cell therapy, gene therapy, or oncolytic virus therapy; 8.Known or suspected to be allergic to or have contraindications to the active ingredients, excipients and imaging examination contrast agents of the study drugs; 9.Those with a history of organ transplantation or those who plan to have an organ transplant during the study; 10.Patients with active infection or uncontrollable infection that require intravenous systemic treatment, or unexplained fever >38.5°C during the screening period or before the first dose; 11.Accompanied by severe coagulopathy or other obvious evidence of bleeding risk; history of gastrointestinal bleeding; any other bleeding event >=CTCAE grade 2 in the past 6 months; 12.Subjects who have received immunosuppressants (such as azathioprine, cyclophosphamide, methotrexate, thalidomide) within 14 days before the first dose; 13.The adverse reactions of previous anti-tumor treatments have not returned to CTCAE 5.0 grade 500IU/ml or the lower detection limit of the research center [only when the lower detection limit of the research center is higher than 500IU/ml]); Active hepatitis C (HCV antibody positive and HCV -RNA>research center detection limit), Treponema pallidum antibody positive; 16.Hypertension that is not well controlled as judged by the researcher (arterial hypertension that is still uncontrolled under standard treatment: systolic blood pressure >=160mmHg and/or diastolic blood pressure >=100mmHg); 17.Have a history of serious cardiovascular disease: such as: ventricular arrhythmia requiring clinical intervention; QTc interval >480ms; acute coronary syndrome, congestive heart failure, stroke within 6 months before the first dose or other cardiovascular events of grade III or above; New York Heart Association (NYHA) cardiac function class = grade II or left ventricular ejection fraction (LVEF) =3; 22.Patients with intracranial brainstem metastasis
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| DLT, MTD, and/or RP2D; the incidence and severity of adverse events (AEs) assessed based on NCI CTCAE version 5.0.; | — |
Secondary
| Measure | Time frame |
|---|---|
| Immunogenicity;Pharmacokinetics (Peripheral Blood);Pharmacokinetics;Pharmacodynamics;Lymphocyte subsets; | — |
Countries
China
Contacts
Public ContactZhao Yanqiu; Chen Lijuan; Xu Xin
Henan Cancer Hospital
Outcome results
None listed