A Clinical Research About CD70-targeted CAR-NKT Cells Therapy in Subjects with Advanced Malignant Solid Tumors

A Clinical Research Evaluating the Safety and Efficacy of CD70-targeted CAR-NKT Cells (CGC738) Therapy in Subjects with Advanced Malignant Solid Tumors

This is a phase I, open-label, single-arm study conducted to evaluate the efficacy, safety and PK of CGC738 in the treatment of advanced malignant solid tumors.

Condition or disease：advanced malignant solid tumors Intervention/treatment：Biological: CD70 CAR-NKT cells Phase：Phase 1

Study Overview

• Status: Recruiting
• Conditions: Advanced Malignant Solid Tumors
• Intervention / Treatment: Biological: CAR-NKT Cells treatment

Detailed Description

This was a dose-expansion study, we plan to enroll 13 to 23 patients with CD70-positive advanced malignant solid tumors to CGC738 treatment. The study was conducted in two stages: dose escalation and dose expansion. Dose escalation involved three dose groups, which were administered using a rapid titration approach combined with the "3+3" design. Revised sentence: "One subject will be enrolled in the initial dose group, and if no dose-limiting toxicity (DLT) occurs within 28 days of the first administration, three additional subjects will be recruited into the subsequent predetermined escalating dose group. A particular dose level will be expanded to 6 patients if one patient out of 3 patients treated at that particular dose level develops DLT. Once this occurs, further dose-escalations are halted until the dose has proven to be safe in the expanded cohort. If 2 or more in a cohort of 6 patients develop DLT no further dose escalation is allowed, and the next lower dose level will be expanded to 6 patients in total. The highest dose among the dose levels tested at which no more than one out of six patients experiences DLT will be considered the MTD. Dose exploration can be discontinued once one or more dose levels with an acceptable safety profile and satisfactory antitumor activity have been selected for subsequent evaluation. During the treatment period of the study, three dose levels of CGC738 will be evaluated. Each of the dose levels will evaluate the safety of the CAR-NKT cells.

The extended study is anticipated to enroll a cohort of 6 to 10 participants. We used leukapheresis for cell collection. The lymphodepletion procedure was conducted using a combination of fludarabine and cyclophosphamide.

• Study Type: Interventional
• Enrollment (Estimated): 13
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Xinan Sheng Professor, MD; Phone Number: +86-10-88196348; Email: doctor_sheng@126.com

Study Locations

• China
  • Beijing, China
    • Recruiting
    • Beijing Cancer Hospital
    • Contact: Xinan Sheng, Professor; Phone Number: 86-13810335676; Email: doctor_sheng@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age 18 to 75 years.
2. ECOG 0-1 points.
3. The expected survival time is more than 3 months.
4. Patients with advanced advanced malignant solid tumor confirmed by histology or cytology to be recurrent or metastatic after at least second-line treatment.
5. IHC: CD70 positive.
6. At least one measurable lesion at baseline per RECIST version 1.1.
7. The functions of important organs are basically normal:
8. Pregnancy tests for women of childbearing age shall be negative, Both men and women agreed to use effective contraception.
9. Subjects or their guardians agree to participate in this clinical trial and sign the ICF, indicating that they understand the purpose and procedures of this clinical trial and are willing to participate in the research.

Exclusion Criteria:

1. Use of cell therapy within the previous one month.
2. Subjects with other malignant tumors within the past 2 years, except basal or squamous skin cancer, superficial bladder cancer, and breast cancer in situ, have been completely cured and do not need follow-up treatment.
3. Patients with leptomeningeal metastasis or central nervous system metastasis, and definite central nervous system underlying diseases with significant symptoms.
4. Immunotherapy, targeted drug therapy or chemotherapy within 5 drug half-lives within 2 weeks before cell infusion.
5. Active hepatitis B, HIV positive and HCV positive.
6. Active infection or uncontrollable infection.
7. Subjects with NYHA heart failure class ≥2 or hypertension uncontrolled by standard therapy requiring special treatment, previous history of myocarditis, or myocardial infarction within 6 months.
8. Unstable respiratory diseases, including interstitial pneumonia.
9. Uncontrolled ascites and pleural effusion
10. Known to have active or uncontrolled autoimmune diseases, such as Crohns disease, rheumatoid arthritis, systemic lupus erythematosus, etc. .
11. Subjects who are using systemic steroids or steroid inhalers for treatment.
12. Pregnant or lactating female subjects.
13. Other investigators deem it unsuitable to participate 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: CAR-NKT Cells Lymphodepleting regimen; Cyclophosphamide + Fludarabine + Infusion of CAR-NKT Cells Lymphodepleting regimen, Cyclophosphamide 250mg/m2 IV on day -5 to -3 and Fludarabine 25mg/m2 IV on days -5 to -3. Followed by infusion of CAR-NKT on day 0.	Biological: CAR-NKT Cells treatment; Cyclophosphamide + Fludarabine + Infusion of CAR-NKT Cells Lymphodepleting regimen, Cyclophosphamide 250mg/m2 IV on day -5 to -3 and Fludarabine 25mg/m2 IV on days -5 to -3. Followed by infusion of CAR-NKT on day 0. Potential CGC738 doses: Dose level 1: 5.0×106 CAR- NKT cells/m2; Dose level 2: 1.5×107 CAR- NKT cells/m2; Dose level 3: 4.5×107 CAR- NKT cells/m2;

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Experiencing Dose Limiting Toxicities (DLTs)	Dose limiting toxicity (DLT) is an AE that meets the following criteria and occurs within 28 days of CGC729 infusion.AE is graded according to CTCAE version 5.0.	Day 28 after CGC738 infusion

Secondary Outcome Measures

Outcome Measure	Time Frame
Assess Objective response rate (ORR)	Day 1 through week 56
Assess Disease control rate (DCR)	Day 1 through week 56
Incidence of adverse events (AEs)	Day 1 through week 56
Cmax, Tmax, AUCS of CD70 CAR-NKT cell dynamics	Day 1 through week 56

Collaborators and Investigators

• Sponsor: Peking University Cancer Hospital & Institute
• Collaborators: Suzhou Cure Genetics Biosciences Co., Limited.

Study record dates

Study Major Dates

• Study Start (Actual): November 14, 2024
• Primary Completion (Estimated): October 17, 2026
• Study Completion (Estimated): October 17, 2026

Study Registration Dates

• First Submitted: November 22, 2024
• First Submitted That Met QC Criteria: December 10, 2024
• First Posted (Estimated): December 11, 2024

Study Record Updates

• Last Update Posted (Estimated): December 11, 2024
• Last Update Submitted That Met QC Criteria: December 10, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: CGC738-IIT-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
• product manufactured in and exported from the U.S.: No