Solid Tumor, Adult Clinical Trial
Official title:
A Pilot Clinical Trial of Autologous EphA-2-Targeting Chimeric Antigen Receptor Dendritic Cell Vaccine Loaded With KRAS Mutant Peptide in Combination With Anti-PD-1 Antibody/Anti-CTLA4 Antibody for Local Advanced/Metastatic Solid Tumors.
This is a pilot clinical trial for subjects with local advanced/metastatic solid tumors to determine the safety, efficacy and immune response of autologous EphA2-targeting CAR-DC vaccine loaded with KRAS mutant peptide (KRAS-EphA-2-CAR-DC) in combination with ICIs. It aims to: assess the safety and antitumor effects of KRAS-EphA-2-CAR-DC vaccine; detect T cell response against KRAS mutant peptide and tumor neoepitopes after the treatment with KRAS-EphA-2-CAR-DC vaccine and ICIs.
Therapeutic cancer vaccines, especially DC-based vaccines, are extensively pursued immune approaches in addition to immune checkpoint blockade antibodies and chimeric antigen receptor T cells. DCs can engulf, process and present tumor antigens to T cells, thereby initiating a potent and tumor-specific immune response. However, clinical outcomes of therapeutic cancer vaccines still remain poor, with objective response rates that rarely exceed ~15%. The maturation and activation of DCs are necessary steps to trigger the antitumor responses. However, it is increasingly clear that tumor-infiltrating dendritic cells (TIDCs) usually have an immature or tolerated phenotype that plays central roles in developing tumor microenvironment (TME). As a consequence, malfunction of TIDCs could suppress the infiltration and function of tumor infiltrating T cells and convert them into immune suppressive regulatory T cells. In our previous research, we constructed novel CAR-DCs (Chimeric antigen receptor engineered dendritic cells) containing a scFv domain targeting EphA2 antigen, CD8a transmembrane, tandem DC-specific activation domains. The engineered CAR-DCs were activated when contacting with tumor targets in TME, and consequently, augmented the cytotoxicity of antigen specific T cells in immune system humanized solid tumor mouse models. Our design of CAR-DCs provides an effective vaccine strategy for solid tumors. Therefore, we designed an autologous CAR-DC vaccine engineered with anti-EphA2 CAR and KRAS mutant peptide (KRAS-EphA-2-CAR-DC) , which can suppress the growth of tumors expressing the correlated KRAS mutant in animal models. In addition, the combination of the immune checkpoint inhibitors could further reverse immunosuppressive TME and globally activate T cell responses. In this pilot study, we aim to assess the safety, efficacy and immune response of KRAS-EphA-2-CAR-DC combined with anti-PD-1 antibody/anti-CTLA4 antibody in patients with local advanced/metastatic solid tumors. ;
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Terminated |
NCT04551885 -
FT516 in Combination With Monoclonal Antibodies in Advanced Solid Tumors
|
Phase 1 | |
| Completed |
NCT05054348 -
First-in-human Study of IO-108 as Single Agent and in Combination With a PD-1 Immune Check Point Inhibitor in Patients With Advanced Solid Tumors
|
Phase 1 | |
| Active, not recruiting |
NCT04474470 -
A Study to Evaluate NT219 Alone and in Combination With ERBITUX® (Cetuximab) in Adults With Advanced Solid Tumors and Head and Neck Cancer
|
Phase 1/Phase 2 | |
| Recruiting |
NCT06088004 -
Phase Ⅰ/Ⅱ Clinical Study to Evaluate ABO2011 Monotherapy in Advanced Solid Tumors
|
Phase 1/Phase 2 | |
| Recruiting |
NCT05055609 -
Open-Label, Dose-Escalation With Expansion to Assess the Safety, Tolerability, and PK of TRE-515 in Subjects With Solid Tumors
|
Phase 1 | |
| Completed |
NCT04020185 -
Safety and Efficacy Study of IMSA101 in Refractory Malignancies
|
Phase 1/Phase 2 | |
| Withdrawn |
NCT05071846 -
MVX-ONCO-2 in Advanced Solid Tumors
|
Phase 1 | |
| Recruiting |
NCT05607199 -
A First in Human Study of AUR 103 Calcium to Evaluate Safety, Pharmacokinetics and Pharmacodynamics
|
Phase 1 | |
| Active, not recruiting |
NCT04552288 -
Study of Benralizumab in People With Skin Side Effects Caused by Cancer Therapies
|
Phase 2 | |
| Active, not recruiting |
NCT06026254 -
A Rollover Study for Subjects Who Completed Participation in IMSA101-101 Trial
|
Phase 1 | |
| Recruiting |
NCT06032845 -
Cryoablation Combined With Tislelizumab Plus Lenvatinib In Previously Treated Solid Tumors (CASTLE-11)
|
Phase 2 | |
| Recruiting |
NCT06144671 -
GT201 Injection For The Treatment Of Advanced Solid Tumors
|
Phase 1/Phase 2 | |
| Not yet recruiting |
NCT06398418 -
R-5780-01 In Combination With PD-1 Checkpoint Inhibitors (Checkpoint Protein on Immune Cells Called T Cells) in Patients With Solid Tumors
|
Phase 1 | |
| Recruiting |
NCT05276284 -
Thiopurine Enhanced Mutations for PD-1/Ligand-1 Efficacy
|
Phase 1/Phase 2 | |
| Recruiting |
NCT04121442 -
Isunakinra Alone and in Combination With a PD-1/PD-L1 Inhibitor in Patients With Solid Tumors
|
Phase 1/Phase 2 | |
| Active, not recruiting |
NCT04221204 -
A Monotherapy in Subjects With Advanced Solid Tumors
|
Phase 1 | |
| Terminated |
NCT03992326 -
Adoptive Transfer Of Autologous Tumor-Infiltrating Lymphocytes in Solid Tumors
|
Phase 1 | |
| Terminated |
NCT05435339 -
A Study to Evaluate Safety, Tolerability, and Preliminary Effect of the GEN1053 Antibody on Malignant Solid Tumors as Monotherapy
|
Phase 1/Phase 2 | |
| Recruiting |
NCT04981119 -
Solid Tumor Analysis for HLA Loss of Heterozygosity (LOH) and Apheresis for CAR T- Cell Manufacturing
|
||
| Recruiting |
NCT06075849 -
Phase I Study to Evaluate Safety and Anti-tumor Activity of PB101, an Anti-angiogenic Immunomodulating Agent
|
Phase 1 |