NKG2D CAR-T(KD-025) in the Treatment of Relapsed or Refractory NKG2DL+ Tumors

One-center, Open-label, Single-arm Clinical Study of the Safety and Effectiveness of NKG2D CAR-T Cells Infusion in the Treatment of Relapsed/ Refractory NKG2DL+ Tumors

This is a Phase 1, single-arm, single-center, open-label study to evaluate the safety and effectiveness of NKG2D-based CAR-T cells infusion in the treatment of relapsed/refractory NKG2DL+ solid tumors.

Study Overview

• Status: Not yet recruiting
• Conditions: Glioma; Hepatocellular Carcinoma; Colorectal Cancer; Solid Tumor
• Intervention / Treatment: Drug: KD-025 CAR-T cells

Detailed Description

In this study,the enrollment of the patients must meet the inclusion and exclusion criteria . All subjects will be asked to continue to undergo long-term gene safety follow-up.

• Study Type: Interventional
• Enrollment (Anticipated): 10
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Baorui Liu, M.D; Phone Number: 61331 +025-83106666 ext 61331; Email: baoruiliu@nju.edu.cn
• Study Contact Backup: Name: Jie Shen, M.D; Phone Number: 61331 +025-83106666; Email: shenjie2008nju@163.com

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China, 210000
      • The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age ≥18, male & female;
2. Patients with recurrent/refractory NKG2DL+ tumors diagnosis by pathological histology or cytology, focus on the inclusion of patients with hepatocellular carcinoma positive. (If recruit liver cancer patients, patients should with locally advanced or metastatic hepatocellular carcinoma (HCC), Barcelona clinic liver cancer (BCLC) staging system classification for B or C, for B, patients are not suitable for local treatment and/or surgery, or disease progression occurs after surgery and/or local treatment, or declined to surgery and/or local treatment);
3. Patients who fail first-line treatment or are unwilling to receive first-line treatment;
4. Disease progression occurred within 14 days before inclusion (RECIST criteria must be used as a basis for assessment of disease progression). According to RECIST V1.1, patients have at least one measurable lesion. Target lesions located within the field of previous therapeutic irradiation or within the area of local treatment (interventional or ablative treatment) are considered measurable if progress is confirmed;

5. The main organs function normally and meet the following requirements;

   Blood routine examination shall be in accordance with (no blood transfusion within 14 days) :

   1. HB≥90g/L
   2. ANC ≥1.5×10^9/L
   3. PLT ≥75×10^9/L

   serum biochemicals examination shall be in accordance with:

   1. BIL <1.5 upper normal limit (ULN)
   2. ALT and AST<2.5×ULN; In the case of liver metastasis, ALT and AST<5×ULN
   3. Serum Cr≤1×ULN, endogenous creatinine clearance≥50ml/min(Cockcroft-Gault formula)；
6. ECOG physical condition score: 0-1;
7. Expected survival time ≥3 months;
8. Cardiac function well before inclusion, no myocardial infarction attack occurred within half a year, and hypertension and other coronary heart disease were under control at present;
9. No other uncontrollable benign diseases such as lung, kidney, liver infection before enrollment;
10. Women of childbearing age must undergo a negative pregnancy test (serum or urine) within 7 days of enrollment and voluntarily use an appropriate method of contraception during observation and within 8 weeks after the last administration; men should be surgically sterilized or agree to use an appropriate method of contraception during the observation period and within 8 weeks after the last administration;
11. Patients voluntarily participated in this trial and sign the informed consent form;
12. Patients with compliance and expected to follow up the efficacy and adverse reactions as required by the protocol；
13. CAR-T cells amplify successfully to the expected number.

Exclusion Criteria:

1. Pregnant or lactating women, pregnancy test positive by blood or urine within 48 hours before immune cell transplantation;
2. Patients who need to be treated with systemic steroid;

3. Under following treatment conditions currently:

   1. during the other anti-tumor clinical observation period within 14 days before blood collection;
   2. patient has not recovered from acute side effects of the previous treatment;
4. Receive radiotherapy within 4 weeks before enrollment;
5. Patients who received any other cell therapy before;
6. Transfection efficiency of lymphocytes of patients < 5% in feasibility assessment screening stage, or T cell amplification efficiency < 5 times；
7. Uncontrolled symptoms or other illnesses, including but not limited to infection, congestive heart failure, unstable angina, arrhythmia, psychosis;
8. Patients with severe acute allergic reactions, or the attending doctor believes there is an unpredictable risk;
9. Patients who have received other cell therapies;
10. Other serious conditions that may limit patient's participation in the study.

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: KD-025 CAR-T cells; NKG2D-based CAR-T cells infusion	Drug: KD-025 CAR-T cells; Autologous genetically modified anti-NKG2DLs CAR transduced T cells

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum tolerated dose (MTD)	Incidence of dose-limiting toxicities	90 days post infusion
The occurrence of AEs and SAEs during the study treatment	An adverse event is any undesirable experience associated with the use of a medical product in a patient	0 to 28 days post infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective remission rate(ORR)	Imaging assessment of tumor remission	1 year post infusion
Progression free survival(PFS)	Progress Free Survival after administration	2 year post infusion
Overall survival (OS)	overall survival refers to the period from being included in the test group to death caused by any reason	2 years post infusion

Collaborators and Investigators

• Sponsor: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
• Collaborators: KAEDI

Study record dates

Study Major Dates

• Study Start (Anticipated): September 25, 2020
• Primary Completion (Anticipated): September 25, 2022
• Study Completion (Anticipated): March 25, 2023

Study Registration Dates

• First Submitted: September 8, 2020
• First Submitted That Met QC Criteria: September 14, 2020
• First Posted (Actual): September 16, 2020

Study Record Updates

• Last Update Posted (Actual): September 23, 2020
• Last Update Submitted That Met QC Criteria: September 20, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma, Hepatocellular
• Other Study ID Numbers: 2020-172-01

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