KSD-101 Therapy for Standard Treatment Failed EBV-associated NPC: an Exploratory Clinical Trial

KSD-101 Therapy for Standard Treatment Failed EBV-associated Nasopharyngeal Carcinoma: an Exploratory Clinical Trial

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Nasopharyngeal Carcinoma
• Intervention / Treatment: Biological: KSD-101

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.

• Study Type: Interventional
• Enrollment (Estimated): 12
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Fei Han; Phone Number: 86 13822113698; Email: hanfei@sysucc.org.cn
• Study Contact Backup: Name: Yali Quan; Phone Number: 86 15871707524; Email: quanyali@kousai.vip

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Sun Yat-sen University Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: KSD-101; Biological: Dendritic Cell Vaccine.Autologous monocyte-derived DCs pulsed with EBV antigen.	Biological: KSD-101; Patients will receive approximately 5x10^6 DC vaccine via subcutaneous injections bi-weekly,total 3-5 times.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The incidence Adverse events (Safety endpoint)	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.	1 year after DC Vaccines injection

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR)	The percentage of participants who achieved PR or better response	1 year after DC Vaccines injection
Disease control rate (DCR)	The percentage of participants who achieved SD or better response	1 year after DC Vaccines injection
Duration of response (DOR)	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	1 year after DC Vaccines injection
Progression-free survival (PFS)	The time from the start of CAR-GPRC5D treatment for the participants to the first time of disease progression or death for any reason	1 year after DC Vaccines injection
Overall survival (OS)	OS is measured from the date of the initial injection of DC Vaccines to the date of the participant's death	1 year after DC Vaccines injection
Levels of EBV-specific CD8+ T cells	EBV-specific CD8+ T cells in peripheral blood will be assessed to monitor changes	1 year after DC Vaccines injection
Levels of B cells	B cells in peripheral blood will be assessed to monitor changes	1 year after DC Vaccines injection
Levels of NK cells	NK cells in peripheral blood will be assessed to monitor changes	1 year after DC Vaccines injection
According to EORTC QLQ-C30	Changes of Quality of life, according to EORTC QLQ-C30	Up to 1 year
According to EQ-5D-5L	Changes of Quality of life, according to EQ-5D-5L	Up to 1 year
According to EORTC QLQ-H&N35	Changes of Quality of life, according to EORTC QLQ-H&N35	Up to 1 year
According to ECOG fitness status	Changes of Quality of life, according to ECOG fitness status	Up to 1 year
EBV-DNA load	changes in EBV-DNA load were assessed during the study	1 year after DC Vaccines injection

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Collaborators: Kousai Bio Co., Ltd.
• Investigators: Principal Investigator: Fei Han, Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2024
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: April 14, 2024
• First Submitted That Met QC Criteria: April 16, 2024
• First Posted (Actual): April 17, 2024

Study Record Updates

• Last Update Posted (Estimated): May 2, 2024
• Last Update Submitted That Met QC Criteria: April 30, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: EBV; Nasopharyngeal Carcinoma
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Nasopharyngeal Neoplasms; Carcinoma; Nasopharyngeal Carcinoma
• Other Study ID Numbers: KSD-101-CR004

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No