NCT05410717

Brief Summary

This study is an open, exploratory clinical study to evaluate the safety and preliminary efficacy of Claudin6, GPC3, Mesothelin, or AXL targeting CAR-NK cells in patients with Claudin6, GPC3, Mesothelin, or AXL-positive advanced solid tumors (ovarian cancer and others)

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
200

participants targeted

Target at P75+ for phase_1

Timeline
122mo left

Started Jun 2022

Longer than P75 for phase_1

Geographic Reach
1 country

1 active site

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress28%
Jun 2022May 2036

Study Start

First participant enrolled

June 1, 2022

Completed
4 days until next milestone

First Submitted

Initial submission to the registry

June 5, 2022

Completed
3 days until next milestone

First Posted

Study publicly available on registry

June 8, 2022

Completed
8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2030

Expected
6 years until next milestone

Study Completion

Last participant's last visit for all outcomes

May 31, 2036

Last Updated

June 25, 2024

Status Verified

June 1, 2024

Enrollment Period

8 years

First QC Date

June 5, 2022

Last Update Submit

June 22, 2024

Conditions

Keywords

Solid tumorClaudin6CAR NKGPC3MesothelinAXLCannabidiolNicotinamide adenine dinucleotideIL7CCL19PD1 antibodyPDL1 antibodyCTLA1 antibody

Outcome Measures

Primary Outcomes (1)

  • Safety by Common Terminology Criteria for Adverse Events (CTCAE) V5.0

    The type, frequency, severity, and duration of adverse events as a result of Claudin6, GPC3, Mesothelin, or AXL- CAR-NK cells infusion will be summarized.

    After CAR-NK cells infusion, up to 52 weeks.

Secondary Outcomes (3)

  • Objective Response Rate (ORR)

    After CAR-NK cells infusion, up to 52 weeks.

  • Disease control rate (DCR)

    up to 52 weeks.

  • Duration of response (DOR)

    up to 36 months

Study Arms (5)

CAR-NK cell therapy group

EXPERIMENTAL

Appropriate patients who could benefit from the Claudin6, GPC3, Mesothelin, or AXL targeting CAR-NK cell therapy against solid cancers are chosen to be the CAR-NK cell therapy group.

Biological: Claudin6, GPC3, Mesothelin, or AXL targeting CAR-NK cells

IL7/CCL19 secreting CAR-NK cell therapy group

EXPERIMENTAL

Appropriate patients who could benefit from the Claudin6, GPC3, Mesothelin, or AXL targeting CAR-NK cell therapy against solid cancers are chosen to be the IL7/CCL19 secreting CAR-NK cell therapy group.

Biological: Claudin6, GPC3, Mesothelin, or AXL targeting CAR-NK cells

PD1/PDL1/CTLA4-scfv secreting CAR-NK cell therapy group

EXPERIMENTAL

Appropriate patients who could benefit from the Claudin6, GPC3, Mesothelin, or AXL targeting CAR-NK cell therapy against solid cancers are chosen to be the PD1/PDL1/CTLA4-scfv secreting CAR-NK cell therapy group.

Biological: Claudin6, GPC3, Mesothelin, or AXL targeting CAR-NK cells

CAR-NK cell plus CBD therapy group

EXPERIMENTAL

Appropriate patients who could benefit from the Claudin6, GPC3, Mesothelin, or AXL targeting CAR-NK cell therapy against solid cancers are chosen to be the CAR-NK cell plus CBD therapy group.

Biological: Claudin6, GPC3, Mesothelin, or AXL targeting CAR-NK cells

CAR-NK cell plus NAD therapy group

EXPERIMENTAL

Appropriate patients who could benefit from the Claudin6, GPC3, Mesothelin, or AXL targeting CAR-NK cell therapy against solid cancers are chosen to be the CAR-NK cell plus NAD therapy group.

Biological: Claudin6, GPC3, Mesothelin, or AXL targeting CAR-NK cells

Interventions

Engineering Claudin6, GPC3, Mesothelin, or AXL targeting CAR combined with/or without IL7/CCL19 and/or scfv against PD1/CTLA4/Lag3 secreting vector into NK cells, which are isolated from patients with advanced ovarian cancer or other cancers with expression of Claudin6, GPC3, Mesothelin, or AXL, and then transfusing them back the patients. In some cases, the CAR-NK cells will be combined with CBD or NAD to enhance the therapeutic efficacy.

CAR-NK cell plus CBD therapy groupCAR-NK cell plus NAD therapy groupCAR-NK cell therapy groupIL7/CCL19 secreting CAR-NK cell therapy groupPD1/PDL1/CTLA4-scfv secreting CAR-NK cell therapy group

Eligibility Criteria

Age18 Years - 75 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • patients with advanced ovarian cancer or other cancers with expression of claudin6.
  • Life expectancy \>12 weeks
  • Adequate heart,lung,liver,kidney function
  • Available autologous transduced NK cells with greater than or equal to 20% expression of Claudin6, GPC3, Mesothelin, or AXL-CAR determined by flow-cytometry and killing of claudin6-positive targets greater than or equal to 20% in cytotoxicity assay
  • Informed consent explained to, understood by and signed by patient/guardian. Patient/guardian given copy of informed consent. -

You may not qualify if:

  • Had accepted gene therapy before;
  • Tumor size more than 25cm;
  • Severe virus infection such as HBV,HCV,HIV,et al
  • Known HIV positivity
  • History of liver/renal transplantation
  • Active infectious disease related to bacteria, virus,fungi,et al
  • Other severe diseases that the investigators consider not appropriate;
  • Pregnant or lactating women
  • Systemic steroid treatment (greater than or equal to 0.5 mg prednisone equivalent/kg/day)
  • Other conditions that the investigators consider not appropriate. -

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

The Second Affiliated Hospital of Guangzhou Medical University

Guangzhou, Guangdong, China

RECRUITING

MeSH Terms

Conditions

Ovarian NeoplasmsTesticular Neoplasms

Interventions

claudin 6Mesothelin

Condition Hierarchy (Ancestors)

Endocrine Gland NeoplasmsNeoplasms by SiteNeoplasmsOvarian DiseasesAdnexal DiseasesGenital Diseases, FemaleFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesGenital Neoplasms, FemaleUrogenital NeoplasmsGenital DiseasesEndocrine System DiseasesGonadal DisordersGenital Neoplasms, MaleGenital Diseases, MaleMale Urogenital DiseasesTesticular Diseases

Intervention Hierarchy (Ancestors)

GPI-Linked ProteinsMembrane GlycoproteinsGlycoproteinsGlycoconjugatesCarbohydratesIntracellular Signaling Peptides and ProteinsPeptidesAmino Acids, Peptides, and ProteinsProteinsLipid-Linked ProteinsMembrane ProteinsAntigens, SurfaceAntigensBiological Factors

Study Officials

  • Zhenfeng Zhang, MD, PHD

    Second Affiliated Hospital of Guangzhou Medical University

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Zhenfeng Zhang, MD, PHD

CONTACT

Bingjia He, MD

CONTACT

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

June 5, 2022

First Posted

June 8, 2022

Study Start

June 1, 2022

Primary Completion (Estimated)

June 1, 2030

Study Completion (Estimated)

May 31, 2036

Last Updated

June 25, 2024

Record last verified: 2024-06

Data Sharing

IPD Sharing
Will not share

Locations