Lung adenocarcinoma
Conditions
Interventions
Dose exploration group 1:Tislelizumab 20mg combined with autologous ?d T cells expanded in vitro
Dose exploration group 2:Tislelizumab 25mg combined with autologous ?d T cells expanded in vitro
Dose exploration group 3:Tislelizumab 33.3mg combined with autologous ?d T cells expanded in vitro
PD-1 inhibitor treatment group:Tislelizumab 200mg
The group treated with ?d T cells combined with PD-1 inhibitors:Tislelizumab combined with autologous ?d T cells expanded in vitro
Sponsors
The Oncology Department, Northern Theater Command General Hospital, People's Liberation Army of China
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Age: 18–75 years old; for those aged 70–75 years old, they must have overall good health and organ functions meeting the standards. 2. Pathological or cytological confirmed inoperable or metastatic lung adenocarcinoma without EGFR mutations; if tissue cannot be obtained, they can be enrolled only when there is sufficient clinical evidence (typical imaging ± tumor markers) and after a multidisciplinary discussion, with a total enrollment not exceeding 5 cases. 3. Confirmed by CT or MRI, at least one measurable lesion, in accordance with RECIST v1.1. 4. ECOG performance status 0–2. 5. Expected survival period >= 6 months. 6. Previous treatment requirements: Have received and failed (progression or intolerance) or are not suitable for current standard systemic treatment; only enrolled when there is sufficient clinical evidence (typical imaging ± tumor markers) and after a multidisciplinary discussion (total enrollment not exceeding 5 cases). a. Chemotherapy/Targeted therapy: Last administration >= 2 weeks (for drugs with long half-life, >= 5 half-lives); b. Immunotherapy: Last administration >= 4 weeks; c. High-dose radiotherapy: >= 2 weeks after completion, and radiation-related toxicity = 4 weeks. 7. Viral and infection status: Hepatitis B: Allowed for those with previous infection or chronic carrier to be enrolled, with HBV DNA not detected or below the detection limit, and receiving concurrent antiviral prophylaxis; active high-level replication (significant increase in HBV DNA) excluded until controlled. Hepatitis C: Can be enrolled, with HCV RNA negative, or RNA positive but receiving antiviral treatment and achieving stable virological control; HIV: Need CD4 count and viral load controlled, and antiretroviral regimen stable for >= 4 weeks, without opportunistic infections; Other active infections need to be controlled before enrollment; it is not recommended to use CMV serological positivity as an exclusion criterion (latent infection is common), and if there is active reactivation of CMV, exclusion until controlled until controlled. 8. Autoimmune and immunosuppression: No active autoimmune disease or history of systemic immunosuppression treatment (> 10 mg prednisone equivalent/day or other immunosuppressants) in the past 2 years; alternative physiological hormones (such as thyroid hormone replacement, adrenal hormone replacement) or local/inhalation steroids allowed. No systemic immunosuppression received >= 2 weeks before enrollment (except equivalent prednisone = 1.5 × 10^9/L; platelets >= 100 × 10^9/L; hemoglobin >= 10 g/dL; Liver function: AST/ALT = 50–60 mL/min; Coagulation: INR = 4 weeks, asymptomatic, not using or reduced to physiological replacement dose of glucocorticoids; no active meningeal/brain parenchymal hemorrhage. 11. Pregnancy and fertility: Enrolled subjects in reproductive age with negative pregnancy test before enrollment, and taking effective contraception for >= 120 days during the study and after the last administration. 12. Agreement and signing of informed consent for
Exclusion criteria
Exclusion criteria: 1. Uncontrolled active infections: including infections requiring intravenous antibacterial/antifungal/antiviral treatment, active tuberculosis, active reactivation of CMV/EBV, or a body temperature > 38.5°C accompanied by evidence of infection. 2. Uncontrolled hepatitis B/hepatitis C/HIV: HBV DNA detectable but not under standardized antiviral treatment; HCV RNA positive and not controlled; HIV viral load not controlled or CD4 10 mg/day); alternative hormones (such as hypothyroidism/adrenal) allowed. 5. Previous solid organ transplantation requiring long-term immunosuppression, or history of allogeneic hematopoietic stem cell transplantation/GVHD. 6. Important organ dysfunction or instability: NYHA III–IV heart failure, myocardial infarction within the past 6 months/ unstable angina pectoris, clinically significant ventricular arrhythmia or QTcF > 480 ms; eGFR 10 mg/day or other immunosuppressants); local/inhalation/short-term prophylaxis allowed. 11. Laboratory abnormalities not meeting the criteria: ANC 5×ULN (without liver metastasis > 2.5×ULN); total bilirubin > 1.5×ULN (except Gilbert syndrome). 12. Other malignant tumors in active stage or under treatment, and may interfere with efficacy/safety assessment (inert epidermal tumors/cured carcinoma in situ etc. can be exceptions, as per protocol settings). 13. Pregnancy or lactation; or reproductive-aged subjects unwilling to use effective contraception during the trial period and within the specified period after the last dose. 14. Severe allergy history: severe allergy to the components of the study drug or cell preparation excipients, or history of severe anaphylaxis/ anaphylactic shock. 15. Inadequate compliance and safety: severe mental disorder or cognitive impairment unable to cooperate with follow-up/signature, or the investigator determines there is an unacceptable treatment risk.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Objective Response Rate; | — |
Secondary
| Measure | Time frame |
|---|---|
| Progression-free survival period;Disease control rate;Duration of remission;Duration of relief;Overall survival rate; | — |
Countries
China
Contacts
Public ContactZhendong Zheng
General Hospital of Northern Theatre Command,People's Liberation Army of China
Outcome results
None listed