Patients with advanced solid tumors, including nasopharyngeal, pulmonary lymphoepithelioma-like, and gastric adenocarcinoma
Conditions
Interventions
Group A: 9×10^6 TCR-T cells /kg:intravenous infusion
Group B: 3×10^7 TCR-T cells /kg(YNMT)· :intravenous infusion
Sponsors
Sun Yat-sen University Cancer Center
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Able to understand the study and have signed the informed consent: 2. Pathologically confirmed advanced metastatic/recurrent nasopharyngeal carcinoma, lung lymphoepitheliomatoid carcinoma or gastric adenocarcinoma; 3. Age =18 years old, =75 years old, male and female: 4. Expected survival =3 months: 5. The physical fitness score of the Eastern Cancer Cooperation Group (ECOG) was 0-1; 6. Positive typing of human leukocyte antigen (HLA); 7. Tumor tissue EBER test was positive and the target test was positive: 8. There is at least one measurable lesion according to RECISTv1.1 standards. In addition, previous radiotherapy-treated lesions cannot be used as target lesions unless imaging studies show significant progression of the lesions. 9. Subjects must have received adequate and failed systematic therapy recommended by clinical guidelines, specifically: Nasopharyngeal cancer: a) The subject has received at least one single or combination of platinum-containing drugs (cisplatin or carboplatin) Progress after combined treatment; b) Patients who are suitable for anti-PD-1 /L1 drugs have received at least one anti-PD-1 /L1 drug Progression of the drug after a monotherapy or combination regimen; c) For subjects with locally advanced nasopharyngeal carcinoma, simultaneous chemoradiotherapy is required after the first treatment And the investigators assessed the subjects as unsuitable for re-treatment; Lung lymphoepitheliomatoid carcinoma: Progress after receiving at least second-line systemic therapy, with specific requirements as follows: a) Driver gene positive: EGFR mutations: gefitinib, erlotinib, ectinib, Afatinib, dacotinib, ocitinib, and ametinib; ALK fusion positive: crizotinib, aletinib, ceretinib and loratinib; ROS1 fusion positive: Entitinib and crizotinib: Had received at least one corresponding small molecule targeted drug and failed treatment, then received containing Second-line systemic treatment of platinum dual chemotherapy ± bevacizumab and progress. b) No driver gene mutation: Have received at least one of the following first-line systemic therapy regimes-pemetrexed plus platinum-based drugs, bevacizumab plus platinum-based drugs, two-drug regimen containing platinum, monotherapy with anti-PD-1 monoclonal antibody or combination regimen. And receive second-line regimencontaining Nabulio/Tirellizumab/docetaxel or pemetrexed after progression and progress; Stomach Cancer: Progress after receiving at least second-line systemic therapy, with specific requirements as follows: a) HER2 positive: received at least one first-line combination chemotherapy regimen of trastuzumab + platinum +5-FU/ capecitabine: b) HER2-negative: patients with PD-L1 CPS=5 who have received at least one first-line combination chemotherapy regimen containing anti-PD-1 monoclonal antibody, platinum, and fluorouracil; Other patients received at least one first-line combination chemotherapy regimen containing platinum or paclitaxel and fluorouracil; Patients received at least one containing paclitaxel/docetaxel/irinotecan after treatment failure Single-agent or combination chemotherapy regimens and progress: 10. At least 2 weeks or 5 half-lives, whichever is longer, since the last antitumor drug was received; 11. Venous access can be established for simple sampling without related contraindications: 12. Agree to take effective contraceptive measures within 6 months from the signing of the informed consent to the BRL03 injection, including the subject (who m
Exclusion criteria
Exclusion criteria: 1. Known or suspected allergy to any of the drugs used in this study; 2. Prior radical radiotherapy <4 weeks, or palliative radiotherapy for non-target lesions <2 weeks for symptom relief; 3. The adverse reactions of previous anti-tumor therapy did not return to CTCAE5.0 criteria = grade 1 (hair loss, peripheral neurotoxicity of grade 2 or below, except toxicity judged by researchers to be of low safety risk); Adoptive cell immunotherapy (including but not limited to CAR-T,TCR-T, etc.) within 4.6 months; 5. Patients with confirmed central nervous system metastases with clinical signs and symptoms who have received treatment and whose symptoms are stable, who have maintained imaging stability for at least 4 weeks before preconditioning, and who do not require corticosteroids to control their symptoms can be enrolled after risk assessment by the investigator; 6. Extensive liver metastases were confirmed (imaging estimates of tumor volume =50% of total liver volume); 7. Have a history of other malignant tumors except carcinoma in situ of cervical cancer or basal cell carcinoma of skin and other malignant tumors with a disease-free survival of more than 5 years; 8. Clinically active infection (except simple urinary tract infection and bacterial pharyngitis), or receiving intravenous anti-infective drugs for infection treatment within 14 days before enrollment; 9. Test positive for hepatitis B or C (HBsAg positive or HBcAb positive, and HBV DNA positive :HCV antibody positive and HCV RNA positive): test positive for HIV, or positive for syphilis antibody; 10. Active, autoimmune disease history requiring systemic treatment (including but not limited to: hemophagocytic lymphohistiocytosis, primary immunodeficiency, inflammatory bowel disease, idiopathic thrombocytopenic purpura, systemic lupus erythematosus, autohemolytic anemia, rheumatoid arthritis, graft-versus-host disease, etc.), Except for thyroid function requiring only thyroid hormone replacement therapy Patients with type 1 diabetes who are hypoactive and require only insulin replacement therapy; 11.NYHA heart function score level 3 or 4; 12. Other serious underlying medical conditions that may limit participants' participation in this study include: Poorly controlled hypertension (systolic blood pressure =160mmHg or diastolic blood pressure =100mmHg after medication); Poorly controlled diabetes: After standard insulin treatment, the fasting blood glucose level was still higher than 11.1mmol/L; Unstable cardiovascular and cerebrovascular diseases: uncontrolled congestive heart failure, myocardial infarction or unstable arrhythmia or unstable angina within the last 6 months, percutaneous coronary intervention, acute coronary syndrome, coronary artery bypass grafting; Cerebrovascular accident, transient ischemic attack, cerebral embolism, deep vein thrombosis, etc. Poorly controlled respiratory diseases: pulmonary embolism, chronic obstructive pulmonary disease, interstitial lung disease, etc.; 13. Long-term use of prednisone or equivalent doses of other glucocorticoids =10mg/ day is required. The exception is adrenal dysfunction requiring glucocorticoid replacement; 14. Subjects have experienced major surgery or severe trauma within 4 weeks prior to the pre-treatment, or are expected to require major surgical intervention during the study period (i.e., surgery requiring the assistance of endotracheal anesthesia); 15. Women with reproductive potential who are pregnant or breastfeeding a
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Dose limiting toxicity;Maximum tolerated dose ;Adverse events (AE); | — |
Secondary
| Measure | Time frame |
|---|---|
| Proliferation and persistence of BRL03 injection in vivo;Serum anti-PD-1SCFV protein concentration;Objective response rate;Disease Control Rate;Duration of Response;Progression-free survival;Time to remission;Overall survival;Incidence of serum anti-BRL03 cells and anti-drug-resistant antibodies (ADA) against anti-PD-1SCFV;RCL occurs;PD characteristics of BRL03 TCR-T cells;Tumor tissue targets, PD-L1 expression levels, and CPS scores, and their associations with safety and efficacy;Plasma EBV DNA content in relation to safety and efficacy.; | — |
Countries
China
Contacts
Public ContactLi Zhang
Sun Yat-sen University Cancer Center
Outcome results
None listed