EBV, Nasopharyngeal Carcinoma (NPC)
Conditions
Brief summary
The main purpse of this study is to evaluate the safety of KSD-101 in patients with EBV-associated Nasopharyngeal Carcinoma,to evaluate the initial clinical outcomes and evaluate the immune response to KSD-101 for the treatment in Patients with EBV-associated Nasopharyngeal Carcinoma.
Detailed description
This is a single-center, single-arm, open, multiple-dose clinical study evaluating the safety, preliminary efficacy, and immune response of KSD-101 for the treatment of patients with EBV-associated nasopharyngeal carcinoma. Approximately 120 mL of PBMCs is collected from subjects. The collected PBMCs are transported to the manufacturing facility for the preparation of KSD-101. Subjects return to the study site for subsequent visits at investigator-notified times. 1. KSD-101 route of administration: subcutaneous injection. 2. KSD-101 treatment dose: 5.0 × 10\^6 cells/dose. 3. KSD-101 treatment frequency: once every 2 weeks for a total of 3-5 times. The 4th and 5th times are booster treatments, which need to be decided by the investigator according to the condition of the subjects.
Interventions
BIOLOGICALKSD-101
Patients will receive approximately 5x10\^6 DC vaccine via subcutaneous injections bi-weekly,total 3-5 times.
Sponsors
Kousai Bio Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Patients or their legal guardian voluntarily participate and sign an informed consent form. 2. Female or emale patients aged 18-70 years (inclusive of the cut-off value) on the date of signing the informed consent. 3. Nasopharyngeal carcinoma confirmed by pathological tissue examination and EBER-positive in tumor tissue by in situ hybridization (ISH or FISH). 4. Nasopharyngeal carcinoma with localized recurrence or localized recurrence with systemic metastasis, or primary metastatic nasopharyngeal carcinoma unsuitable for localized or radical treatment, for which there is no effective treatment and which is seriously life-threatening. 5. At least one measurable lesion according to RECIST v1.1 criteria. 6. An Eastern Cooperative Oncology Group (ECOG) score of 0 to 1. 7. Have criteria for single or venous blood collection and have no other contraindications to cell collection. 8. Patients' laboratory findings are compatible: (1)Blood routine: neutrophils ≥ 1.5×10\^9/L, hemoglobin ≥ 90g/L, platelets ≥ 100×10\^9/L. (2)Liver function: ALT, AST ≤ 3 × ULN and total bilirubin ≤ 1.5 × ULN. (3)Renal function: creatinine ≤ 1.5 × ULN. (4)Cardiac function: left ventricular ejection fraction (LVEF) ≥ 40%. (5)Coagulation function: fibrinogen ≥ 1.0g/L, activated partial thromboplastin time (APTT) ≤ 1.5 × ULN, prothrombin time (PT) ≤ 1.5 × ULN. 9.Patients' corresponding lymph node region can accommodate subcutaneous injections. 10.Expected survival ≥ 3 months.
Exclusion criteria
1. Patients receiving any anti-tumor therapy such as chemotherapy, radiotherapy, immunosuppressive therapy, etc. within 4 weeks prior to mono-collection. 2. Women who are pregnant (positive urine/blood pregnancy test), breastfeeding, or men or women who are planning to conceive within the last 1 year. 3. Active hepatitis B (HbsAg or HbcAb positive and HBV DNA ≥100 IU/mL), active hepatitis C (HCV antibody positive and peripheral blood HCV RNA positive); human immunodeficiency virus (HIV) antibody positive; syphilis test positive. 4. Patients with central nervous system pathology (e.g., cerebral edema, need for hormonal intervention, or progression of brain metastases). 5. Patients with uncontrollable infectious disease within 4 weeks prior to enrollment, or with active tuberculosis or on anti-tuberculosis therapy. (\< CTCAE grade 2 genitourinary infections and upper respiratory tract infections, except EBV infections). 6. Patients have a serious underlying disease (cardiovascular disease, respiratory disease, renal insufficiency, coagulation abnormality, autoimmune disease or immunodeficiency disease, etc.). 7. Other active malignant tumors within the past 3 years, unless they are curable tumors and have been significantly cured, such as basal or squamous cell carcinoma, carcinoma in situ of the uterine cervix or breast. 8. Subjects who have undergone major surgery or severe trauma within 4 weeks prior to enrollment or are expected to require major surgical intervention (i.e., surgery requiring the assistance of endotracheal anesthesia) during the study period. 9. Patients have received a prophylactic live or live attenuated vaccine within 4 weeks prior to screening. 10. Patients have participated in another clinical study within 4 weeks prior to screening. 11. Patients with a prior history of severe drug allergy, or penicillin allergy. 12. Patients have substance abuse/addiction. 13,Patients have other conditions that, in the judgment of the investigator, make enrollment inappropriate.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The incidence Adverse events (Safety endpoint) | 1 year after DC Vaccines injection | Adverse events will be graded according to the NCI-CTCAE 5.0 grading criteria throughout the study period, except for injection site (localized) adverse events, which will be graded with reference to the Guidelines for Grading Criteria for Adverse Events in Clinical Trials of Vaccines for Prophylaxis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective response rate (ORR) | 1 year after DC Vaccines injection | The percentage of participants who achieved PR or better response |
| Disease control rate (DCR) | 1 year after DC Vaccines injection | The percentage of participants who achieved SD or better response |
| Duration of response (DOR) | 1 year after DC Vaccines injection | DOR will be calculated among responders (with a PR or better response) from the date of initial documentation of a response (PR or better) to the date of first documented evidence of progressive disease |
| Progression-free survival (PFS) | 1 year after DC Vaccines injection | The time from the start of CAR-GPRC5D treatment for the participants to the first time of disease progression or death for any reason |
| Overall survival (OS) | 1 year after DC Vaccines injection | OS is measured from the date of the initial injection of DC Vaccines to the date of the participant's death |
| Levels of EBV-specific CD8+ T cells | 1 year after DC Vaccines injection | EBV-specific CD8+ T cells in peripheral blood will be assessed to monitor changes |
| EBV-DNA load | 1 year after DC Vaccines injection | changes in EBV-DNA load were assessed during the study |
| Levels of NK cells | 1 year after DC Vaccines injection | NK cells in peripheral blood will be assessed to monitor changes |
| According to EORTC QLQ-C30 | Up to 1 year | Changes of Quality of life, according to EORTC QLQ-C30 |
| According to EQ-5D-5L | Up to 1 year | Changes of Quality of life, according to EQ-5D-5L |
| According to EORTC QLQ-H&N35 | Up to 1 year | Changes of Quality of life, according to EORTC QLQ-H&N35 |
| According to ECOG fitness status | Up to 1 year | Changes of Quality of life, according to ECOG fitness status |
| Levels of B cells | 1 year after DC Vaccines injection | B cells in peripheral blood will be assessed to monitor changes |
Contacts
Primary ContactHaiyan Hu
Outcome results
None listed