Clinical trial NCT06097793: KSD-101 Therapy for EBV-associated Nasopharyngeal Carcinoma: an Exploratory Clinical Trial
Official title: KSD-101 Therapy for EBV-associated Nasopharyngeal Carcinoma: an Exploratory Clinical Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: EARLY_PHASE1
Conditions: Nasopharyngeal Carcinoma
Keywords: EBV
Nasopharyngeal Carcinoma
Lead sponsor: Kousai Bio Co., Ltd.
Sponsor class: OTHER
First posted: 2023-10-24
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Enrolled subjects will receive a peripheral blood single nucleated cell collection (D-20) of approximately 120-150 ml. After the single collection is transported to the dendritic cell vaccine preparation party via the cold chain, a dendritic cell vaccine (KSD-101) will be prepared using the subject's own single nucleated cells. After successful preparation of KSD-101, the subject will return to the hospital for KSD-101 reinfusion as follows.

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.

Eligibility criteria: Inclusion Criteria:

1. Patients or their legal guardians voluntarily participate and sign the informed consent form.
2. male or female 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. have an Eastern Cooperative Oncology Group (ECOG) score: 0-1.
7. have criteria for single or venous blood collection and have no other contraindications to cell collection.
8. the patient's laboratory findings are compatible:

   * Blood routine: neutrophils ≥ 1.0×10\^9/L, hemoglobin ≥ 80g/L, platelets ≥ 50×10\^9/L.
   * Liver function: ALT, AST ≤ 3 × ULN and total bilirubin ≤ 1.5 × ULN.
   * Renal function: creatinine ≤ 1.5 × ULN.
   * Cardiac function: left ventricular ejection fraction (LVEF) ≥ 40%.
   * Coagulation function: fibrinogen ≥ 1.0g/L, activated partial thromboplastin time (APTT) ≤ 1.5 × ULN, prothrombin time (PT) ≤ 1.5 × ULN.
9. The patient's corresponding lymph node region can meet the demand for subcutaneous injection.

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. the patient has 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. the patient has received a prophylactic live or live attenuated vaccine within 4 weeks prior to screening.
10. the patient has 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. the patient has substance abuse/addiction.
13. patients with other conditions that, in the judgment of the investigator, make them unsuitable for inclusion.

Primary outcomes:
measure: Safety endpoint
timeFrame: 1 year after DC Vaccines injection
Secondary outcomes:
measure: EBV-DNA load
timeFrame: 1 year after DC Vaccines injection
measure: Objective response rate (ORR)
timeFrame: 1 year after DC Vaccines injection
measure: Disease control rate (DCR)
timeFrame: 1 year after DC Vaccines injection
measure: Duration of response (DOR)
timeFrame: 1 year after DC Vaccines injection
measure: Progression-free survival (PFS)
timeFrame: 1 year after DC Vaccines injection
measure: Overall survival (OS)
timeFrame: 1 year after DC Vaccines injection
measure: Levels of EBV-specific CD8+ T cells
timeFrame: 1 year after DC Vaccines injection
measure: Levels of B cells
timeFrame: 1 year after DC Vaccines injection
measure: Levels of NK cells
timeFrame: 1 year after DC Vaccines injection
measure: According to EORTC QLQ-C30
timeFrame: Up to 1 year
measure: According to EQ-5D-5L
timeFrame: Up to 1 year
measure: According to EORTC QLQ-H&N35
timeFrame: Up to 1 year
measure: According to ECOG fitness status
timeFrame: Up to 1 year
Other outcomes:
Locations:
city: Wuhan
country: China
facility: Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
Study officials:
affiliation: Tongji Hospital
name: Guangyuan Hu
role: PRINCIPAL_INVESTIGATOR
References: