Solid Tumor
Conditions
Keywords
Melanoma, non-small cell lung cancer, NSCLC, Neoantigen, Adoptive T cell Therapy
Brief summary
The primary objective of this study is to evaluate the safety of Neo-T in the treatment of advanced solid tumors. The secondary objective of this study is to evaluate preliminarily the effect of Neo-T in the treatment of advanced solid tumors.
Detailed description
This is a single arm, open label and non-randomized clinical study with two parts. In Part A, 6 subjects with advanced solid tumors will be enrolled to assess the safety and explore maximum tolerated dose(MTD) or recommended dose of Neo-T. Depending on results in Part A, the study may proceed to Part B, where 15 subjects with advanced solid tumors will be enrolled to evaluate the effect of Neo-T.
Interventions
BIOLOGICALNeo-T
Patients will recive Neo-T iv on day 0. Three times of cell infusion with an interval of 7 days constitute a cycle,maximum four cycles of treatment for patients.
DRUGCyclophosphamide
Cyclophosphamide 500 mg/m2/day iv on day-5 for one day.
DRUGFludarabine
Fludarabine 25 mg/m2/day iv on day-5 and day-4 for two days.
DRUGInterleukin-2
500,000IU/m2 SC,after each cell infusion,IL-2 will start within 24 hours and every 8-12 hours for up to 6 doses.
Sponsors
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
BGI, China
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Greater than or equal to 18 years of age and less than or equal to 75 years of age; all genders. 2. Advanced solid tumors including but not limited to some high frequency somatic mutations,such as melanoma,driver mutation-negative non-small cell lung cancer. 3. Advanced solid tumors patients who are HLA - A0201 /A1101/A2402 subtypes. 4. Measurable solid tumors with at least one lesion that is resectable or tumor biopsies for DNA extraction. 5. Patients who failed or were intolerant to standard treatment. 6. Possess venous access for mononuclear cell collection or intravenous blood collection. 7. Patients (or their legal representatives) who are able to understand and sign the Informed Consent Form and willing to sign a durable power of attorney. 8. Clinical performance status of ECOG is 0 or 1. 9. Patients who are able to cooperate to observe adverse reactions and the effect of the treatment,expected lifetime is greater than six month. 10. Patients of both genders must be willing to practice birth control from the time of enrollment to three months after treatment on this study,a fertile woman must have a negative pregnancy test. 11. The laboratory test values and the functions of important organs meet the following requirements:1）Serology: HIV antibody(-), hepatitis B DNA(-), hepatitis C antibody(-) and no active syphilis infection; 2）Hematology: Absolute neutrophil count is greater than or equal to 1.5×10\^9/L; WBC is greater than or equal to 3×10\^9/L; lymphocyte count is greater than or equal to 0.8×10\^9/L; Platelet count is greater than or equal to 80×10\^9/L; Hemoglobin is greater than or equal to 90g/L ; 3）Chemistry: Serum ALT/AST is less than or equal to 3 times ULN,except in patients with liver metastasis who must have ALT/AST less than or equal to 5 times ULN; Serum Creatinine is less than or equal to 1.5 times ULN ; Total bilirubin is less than or equal to 1.5 times ULN, except in patients with Gilbert's Syndrome who must have a total bilirubin less than 3 times ULN;4）Blood Clotting Parameters:Prothrombin Time(PT) and International Normalised Ratio (INR) are less than or equal to 1.5 times ULN;Activated Partial Thromboplastin Time (APTT) is less than or equal to 1.5 times ULN;For subjects who frequently take anticoagulant drugs,their blood clotting parameters can meet the value range adptive to this special population;5）Left ventricular ejection fraction（LVEF）is more than or equal to 50%. 12. More than four weeks must have elapsed since any prior systemic therapy at the time the patient receives the lymphodepletion regimen, and toxicities must have recovered to grade 1 or less (except for toxicities such as alopecia or vitiligo).
Exclusion criteria
1. Pregnant or lactating women. 2. History of severe immediate hypersensitivity reaction to Neo-T and any of the agents used in this study. 3. Subjects with a history of organ transplantation. 4. Subjects with unstable brain metastases. 5. Any active autoimmune disease or subjects with a history of autoimmune diseases that have been assessed by the investigator to be unsuitable for this study.Including but not limited to the following diseases: such as systemic lupus erythematosus, immune related neuropathy, multiple sclerosis, Guillain Barre syndrome, myasthenia gravis, connective tissue diseases, inflammatory bowel diseases(Crohn's disease and ulcerative colitis), excluding vitiligo, eczema, type I diabetes, rheumatoid arthritis and other joint diseases, Sjogren's syndrome and controlled psoriasis by local medication. 6. Active systemic infections,for example, acute infections requiring systemic antibiotic, antiviral, or antifungal treatment occur within 2 weeks before enrollment. 7. Severe liver and kidney function damage(gived treatment is still uncontrollable,and biochemical indicators cannot meet the
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with adverse events as assessed by CTCAE v5.0. | one month | Keep records the adverse events experienced by subjects in 28 days after the first infusion. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate(ORR) | one year | ORR is defined as the proportion of participants with tumor size reduction(CR,PR) assessed by RECIST 1.1 and iRECIST. |
| Disease Control Rate(DCR) | one year | DCR is defined as the proportion of participants with tumor size reduction(CR,PR) and stable disease(SD) assessed by RECIST 1.1 and iRECIST. |
| overall survival(OS) | one year | The time from the first infusion of Investigational Product until death. |
| progression-free survival(PFS) | one year | PFS is defined as the time from the first infusion of Investigational Product until objective tumor progression, as assessed by RECIST 1.1 and iRECIST, or death, whichever occurs first. |
| Duration of Response(DOR) | one year | DOR refers to the period from the first evaluation of tumor as CR or PR to the first evaluation as PD(Progressive Disease) per RECIST1.1 and iRECIST. |
Countries
China
Contacts
Primary ContactJing Chen, Doctor
Outcome results
None listed