Clinical trial NCT06370026: KSD-101 Therapy for Standard Treatment Failed EBV-associated NPC: an Exploratory Clinical Trial
Official title: KSD-101 Therapy for Standard Treatment Failed EBV-associated Nasopharyngeal Carcinoma: an Exploratory Clinical Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: EARLY_PHASE1
Conditions: Nasopharyngeal Carcinoma
Keywords: EBV
Nasopharyngeal Carcinoma
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
Collaborators: name: Kousai Bio Co., Ltd.
First posted: 2024-04-17
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.

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.

Eligibility criteria: 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 that has failed 3rd or more line treatment and has localized recurrence or localized recurrence with systemic metastasis or primary metastatic nasopharyngeal carcinoma that is not suitable for localized or radical treatment.
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:

   * Blood routine: neutrophils ≥ 1.5×10\^9/L, hemoglobin ≥ 90g/L, platelets ≥ 100×10\^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. 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.

Primary outcomes:
measure: The incidence Adverse events (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: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Center
state: Guangdong
Study officials:
affiliation: Sun Yat-sen University
name: Fei Han
role: PRINCIPAL_INVESTIGATOR
References: