Ignite Creation Date:
2024-05-06 @ 3:47 PM
Last Modification Date:
2024-10-26 @ 1:56 PM
Study NCT ID:
NCT04751786
Status:
RECRUITING
Last Update Posted:
2024-04-10
First Post:
2020-12-11
Brief Title:
Dose Escalation Study of Immunomodulatory Nanoparticles
Sponsor:
Radboud University Medical Center
Organization:
Radboud University Medical Center
Study Overview
Official Title:
First-in-human Phase I Dose Escalation Study Assessing Safety Tolerability and Preliminary Efficacy of Immunomodulatory Nanoparticles
Status:
RECRUITING
Status Verified Date:
2024-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
PRECIOUS-01
Brief Summary:
PRECIOUS-01 is an immunomodulating agent composed of the invariant natural killer T cell iNKT activator threitolceramide-6 ThrCer6 IMM60 and the New York Esophageal Squamous Cell Carcinoma-1 NY-ESO-1 cancer-testis antigen peptides encapsulated in a polylactic-co-glycolic acid PLGA nanoparticle
PRECIOUS-01 is being developed for the treatment of patients with NY-ESO-1-positive cancers
PRECIOUS-01 is being developed for the treatment of patients with NY-ESO-1-positive cancers
Detailed Description:
In the rapidly evolving treatment landscape of advanced solid tumors immunotherapeutic approaches have revolutionized cancer care for patients Despite these advances there is an undiminished need for the development of novel immunotherapeutic treatment modalities that are able to orchestrate effective anti-tumor immune responses The investigators study a new class of immunomodulatory nanomedicines PLGA nanoparticles loaded with a tumor antigen and an iNKT cell agonist
PLGA is a biodegradable polymer with minimal systemic toxicity approved by the Food and Drug Administration FDA as well as the European Medicines Agency EMA to be used in various drug-carrying platformsTumor antigens and immunomodulatory molecules can be co-encapsulated in PLGA-based nanoparticles In preclinical studies these PLGA-based nanoparticles can induce anti-tumor immune responses The investigators aim to explore PLGA-based nanoparticles containing the tumor antigen NY-ESO-1 and the iNKT cell activator IMM60 for their capacity to induce anti-tumor responses in cancer patients
NY-ESO-1 is a cancer-testis antigen normally expressed in testicular germ cells and trophoblasts of the placenta However NY-ESO-1 is also expressed in a wide range of cancers with a high incidence around 25-30 of several advanced cancers such as melanoma 40 lung 2-32 bladder 32-35 and ovarian 30 cancer NY-ESO-1 is able to elicit immune responses Patients who have NY-ESO-1-positive tumors have spontaneous or vaccine-induced humoral and cellular immune responses against this antigen Therefore NY-ESO-1 is considered to be a suitable tumor antigen for further clinical evaluation Clinical trials have already shown the safety and tolerability of the NY-ESO-1 protein and peptides in patients with advanced cancer
In order to generate NY-ESO-1-directed immune responses the NY-ESO-1 protein is taken up by antigen-presenting cells APCs and processed in small protein fragments peptides Particular peptides can bind to patient-specific HLA molecules and subsequently this HLA-peptide complex is recognized at the cell membrane by the T cell receptor TCR of T cells Once the TCR specifically binds to the HLA-peptide complex the T cell becomes stimulated and exerts its function ie tumor cell killing by CD8 T cells In 1 an overview of the peptides known to bind to certain HLA alleles and recognized by T cells either by CD4 or by CD8 T cells is presented
Particulate vaccines are known to elicit better immune responses due to higher uptake by APCs Encapsulating antigens and adjuvants within the same polymeric nanoparticle can enhance T cell responses In earlier studies the NY-ESO-1 whole protein was encapsulated in adjuvant ISCOMATRIX and shown to induce specific T cell responses in a majority of patients iNKT cell agonists are more suitable adjuvants due to their higher activity in low doses and activation of DCs by iNKT cells In this respect the investigators will employ PLGA nanoparticles loaded with the NY-ESO-1 antigen and the iNKT cell agonist IMM60 as a co-delivery system
To facilitate NY-ESO-1 antigen encapsulation long 85-111peptide 2 and 117-143peptide 3 and short 157-165peptide 4 peptides will be incorporated into nanoparticles In combination the three selected NY-ESO-1-derived peptides are presented in 80 of the class I and class II HLA alleles of the European population Similar peptides 79-116 and 118-143 were previously loaded onto DCs together with α-GalCer and delivered to cancer patients in a recent clinical trial The results of that trial demonstrated iNKT cell expansion CD4 T cell responses against the 118-143 peptide in 78 patients and CD8 T cell responses against the 79-116 peptide in 38 patients Gasser Sharples et al 2018 Here an additional short peptide 157-165 is included which is presented by the highly prevalent HLA-A21 molecule Hence higher CD8 T cell responses against this epitope and superior activation of human iNKT cells by IMM60 are expected due to co-encapsulation
PLGA is a biodegradable polymer with minimal systemic toxicity approved by the Food and Drug Administration FDA as well as the European Medicines Agency EMA to be used in various drug-carrying platformsTumor antigens and immunomodulatory molecules can be co-encapsulated in PLGA-based nanoparticles In preclinical studies these PLGA-based nanoparticles can induce anti-tumor immune responses The investigators aim to explore PLGA-based nanoparticles containing the tumor antigen NY-ESO-1 and the iNKT cell activator IMM60 for their capacity to induce anti-tumor responses in cancer patients
NY-ESO-1 is a cancer-testis antigen normally expressed in testicular germ cells and trophoblasts of the placenta However NY-ESO-1 is also expressed in a wide range of cancers with a high incidence around 25-30 of several advanced cancers such as melanoma 40 lung 2-32 bladder 32-35 and ovarian 30 cancer NY-ESO-1 is able to elicit immune responses Patients who have NY-ESO-1-positive tumors have spontaneous or vaccine-induced humoral and cellular immune responses against this antigen Therefore NY-ESO-1 is considered to be a suitable tumor antigen for further clinical evaluation Clinical trials have already shown the safety and tolerability of the NY-ESO-1 protein and peptides in patients with advanced cancer
In order to generate NY-ESO-1-directed immune responses the NY-ESO-1 protein is taken up by antigen-presenting cells APCs and processed in small protein fragments peptides Particular peptides can bind to patient-specific HLA molecules and subsequently this HLA-peptide complex is recognized at the cell membrane by the T cell receptor TCR of T cells Once the TCR specifically binds to the HLA-peptide complex the T cell becomes stimulated and exerts its function ie tumor cell killing by CD8 T cells In 1 an overview of the peptides known to bind to certain HLA alleles and recognized by T cells either by CD4 or by CD8 T cells is presented
Particulate vaccines are known to elicit better immune responses due to higher uptake by APCs Encapsulating antigens and adjuvants within the same polymeric nanoparticle can enhance T cell responses In earlier studies the NY-ESO-1 whole protein was encapsulated in adjuvant ISCOMATRIX and shown to induce specific T cell responses in a majority of patients iNKT cell agonists are more suitable adjuvants due to their higher activity in low doses and activation of DCs by iNKT cells In this respect the investigators will employ PLGA nanoparticles loaded with the NY-ESO-1 antigen and the iNKT cell agonist IMM60 as a co-delivery system
To facilitate NY-ESO-1 antigen encapsulation long 85-111peptide 2 and 117-143peptide 3 and short 157-165peptide 4 peptides will be incorporated into nanoparticles In combination the three selected NY-ESO-1-derived peptides are presented in 80 of the class I and class II HLA alleles of the European population Similar peptides 79-116 and 118-143 were previously loaded onto DCs together with α-GalCer and delivered to cancer patients in a recent clinical trial The results of that trial demonstrated iNKT cell expansion CD4 T cell responses against the 118-143 peptide in 78 patients and CD8 T cell responses against the 79-116 peptide in 38 patients Gasser Sharples et al 2018 Here an additional short peptide 157-165 is included which is presented by the highly prevalent HLA-A21 molecule Hence higher CD8 T cell responses against this epitope and superior activation of human iNKT cells by IMM60 are expected due to co-encapsulation
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 2017-002568-41 | EUDRACT_NUMBER | None | None |