AzTrials
AzTrials

Advanced Solid TumorPhase 1PRECIOUS-01NCT04751786

Dose Escalation Study of Immunomodulatory Nanoparticles

A Phase 1 study testing PRECIOUS-01 in people with Advanced Solid Tumor, run by Radboud University Medical Center at 1 site in Netherlands.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial 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 poly(lactic-co-glycolic acid) (PLGA) nanoparticle. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Advanced Solid Tumor
What is being tested?
PRECIOUS-01
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
15 participants
Where
1 siteNetherlands
Study dates
11 Jan 2021to Dec 2026
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Age 18 years or older at time of signing informed consent.
  • Performance status (ECOG 0 or 1).
  • Estimated life expectancy of at least 6 months.
  • Histologically or cytologically confirmed advanced and /or metastatic solid tumor with progressive disease at baseline, for whom no standard treatment is available.
  • IHC-confirmed NY-ESO-1 positivity prior to screening (cut-off value: 1% positive cells) on (archival) tumor tissue, per local laboratory guidelines.
  • Subject with evaluable disease per RECIST v1.1.
Show all 19Show fewer
  • Adequate hematologic, renal and liver function as defined by laboratory values performed within 14 days of start of treatment:
  • Hemoglobin (Hb) ≥ 6 mmol/L;
  • Absolute Lymphocyte Count (ALC) > 0.8 x 109/L;
  • Absolute Neutrophil Count (ANC) ≥ 1.5 × 109/L;
  • Platelet count > 100 x 109/L;
  • Creatinine level within normal institutional limit;
  • Serum bilirubin < 25 μmol/L;
  • Serum Lactic Acid Dehydrogenase (LDH) ≤ Upper Limit of Normal range (ULN);
  • Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), and Alanine Aminotransferase (ALT) ≤ ULN unless related to liver metastasis (in which case levels should be < 3 ULN).
  • Previous therapy-derived toxicities should be resolved to Grade < 2 according to CTCAE v5.0, with exceptions for alopecia.
  • All subjects of childbearing potential (defined as < 2 years after last menstruation or not surgically sterile) must have a negative highly sensitive pregnancy test at screening (urine/serum) and agree to use a highly effective method for contraception according to the EU Clinical Trial Facilitation Group guidance from time of signing the informed consent form (ICF) until at least 120 days after the last administration of PRECIOUS-01. The partners of subjects with childbearing potential must also apply contraceptive methods, and are recommended not to donate sperm.
  • Before registration, ability of subject to give written informed consent according to International Council for Harmonisation (ICH) Good Clinical Practice (GCP), and national rules/local regulations.
  • Expected adequacy of follow-up.

Who cannot join

  • Second malignancy in the previous 2 years, with the exception of adequately treated in situ carcinoma of the cervix uteri and basal or squamous cell carcinoma of the skin,
  • Clinical suspicion or radiological evidence of active brain metastases. Patients with brain metastases that have been treated previously and are proven stable (computed tomography [CT] or magnetic resonance imaging [MRI] < 30 days) and without steroids for > 3 months are allowed.
  • Subjects with thromboembolic events within the past year.
  • Subjects on any other anticancer therapy (cytotoxic, biologic or investigational agents), unless at least 4 weeks (or 5 half-lives, whichever is shorter, 6 weeks for mitomycin-C or nitrosoureas), have elapsed since the last dose before the first administration of PRECIOUS-01. At least 4 weeks should have elapsed since receiving palliative radiotherapy. Chronic treatment with non-investigational gonadotropin-releasing hormone analogs or other hormonal or supportive care is permitted.
  • Subjects with major surgery within 4 weeks before initiating treatment or with minor surgical procedure within 7 days before initiating treatment (except for port-a-cath or central line i.v. placement, or biopsy), or anticipation of the need for major surgery during the course of the trial treatment.
  • Concomitant use of oral or i.v. immunosuppressive drugs. Inhaled, topical or intranasal steroids and adrenal replacement steroids < 10 mg/day (prednisone equivalent) are permitted in the absence of auto-immune disease.
Show all 19Show fewer
  • Uncontrolled infectious disease, i.e. negative testing for human immunodeficiency virus (HIV), Hepatitis B Virus (HBV), Hepatitis C Virus (HCV) and syphilis (Treponema Pallidum Hemagglutination Assay [TPHA]).
  • (Systemic) autoimmune disease such as, but not limited to, inflammatory bowel disease, multiple sclerosis and lupus. Subjects with type 1 diabetes mellitus, hypothyroidism after autoimmune thyroiditis and skin disorders (eczema and psoriasis) are not excluded.
  • History of clinically significant cardiovascular disease (≤ 6 months prior to Day 1 on trial) such as stroke, Transient Ischemic Attack (TIA), unstable angina, New York Heart Association (NYHA) Grade II or greater congestive heart failure, myocardial infarction, uncontrolled hypertension, cardiac arrhythmia requiring medication, relevant pathological ECG findings or uncontrolled hypertension (systolic > 150 mm Hg and/or diastolic > 100 mm Hg).
  • Serious (bleeding and clotting) condition(s) that may interfere with safe administration of PRECIOUS-01.
  • Abnormal or clinically significant coagulation parameters at the discretion of the Clinical Investigator, i.e.:
  • Prothrombin Time - International Normalized Ratio (PT-INR)
  • Activated Partial Thromboplastin Time (APTT)
  • Subjects being treated with anticoagulants are excluded if the coagulation parameters are outside the therapeutic intervals as described in the Summary of Product Characteristics (SmPC) for the administered treatment.
  • Evidence of any other conditions (such as psychological/familial sociological/geographical issues, psychiatric illness, infectious diseases, physical examination or laboratory findings) that may interfere with the planned treatment, affect subject compliance or place the subject at high risk from treatment-related complications. These conditions must be discussed with the subject before registration in the trial.
  • History of severe allergic episodes and/or Quincke's edema.
  • Prior allogeneic tissue/solid organ transplant, stem cell or bone marrow transplant.
  • Known hypersensitivity to any component of PRECIOUS-01.
  • Pregnant or lactating women. A serum pregnancy test should be performed within 7 days prior to start of trial treatment for confirmation in case of childbearing potential.

Trial locations and contacts

1 site in 1 country.

Netherlands1 site

  • Radboudumc

    Nijmegen, Gelderland, 6525 GA

Other trials in Netherlands

About this study

Official title: First-in-human Phase I Dose Escalation Study Assessing Safety, Tolerability and Preliminary Efficacy of Immunomodulatory Nanoparticles

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 poly(lactic-co-glycolic acid) (PLGA) nanoparticle.

PRECIOUS-01 is being developed for the treatment of patients with NY-ESO-1-positive cancers.

Read the 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 platforms.Tumor 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, i.e. 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 (85-111(peptide #2) and 117-143(peptide #3)) and short (157-165(peptide #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 7/8 patients, and CD8+ T cell responses against the 79-116 peptide in 3/8 patients (Gasser, Sharples et al. 2018). Here, an additional short peptide (157-165) is included, which is presented by the highly prevalent HLA-A2.1 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.

Being tested
PRECIOUS-01
Keywords
Advanced solid tumor, No standard treatment available, Phase I dose escalation study, IHC-confirmed NY-ESO-1 positivity

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PRECIOUS-01Drug

    Subjects will be enrolled in one of three dosing cohorts (three subjects per cohort for the planned dose escalation with a planned extension to a total of six subjects for the two highest dosing cohorts for the evaluation of the pharmacodynamic effects of PRECIOUS-01 for determination of the RP2D, if MTD is not reached).

Study groups in NCT04751786
Study groupRoleWhat they receive
PRECIOUS-01ExperimentalEligible subjects will receive three i.v. infusions of PRECIOUS-01 at a 3-weekly interval in three dose-finding cohorts (low: 0.4 mg/kg, intermediate: 0.8 mg/kg, and high: 1.6 mg/kg fixed doses). Subjects will be monitored for safety and the occurrence of Dose-Limiting Toxicities (DLTs). A 3+3 design is used for the dose escalation steps. Three subjects will be enrolled sequentially per cohort. If the maximum tolerated dose (MTD) is not reached in the planned dose escalation cohorts, the RP2D will be based on the observed safety and immune modulatory activity as pharmacodynamic parameter supporting the RP2D. The sample size is based on the determination of the MTD/RP2D. In order to collect sufficient information regarding changes in immune related parameters as readout for pharmacodynamics of the particles, it is planned to extend the two highest dosing cohorts to a total of six subjects or to extend the highest dosing cohort to a total of nine subjects, depending on observed toxicity
Receives: Drug: PRECIOUS-01

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Safety of PRECIOUS-01

    The incidence of treatment-emerging Adverse Events (AEs) according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v5.0 reporting severity and relatedness

    Measured: From enrollment up to and including 21 days after last PRECIOUS-01 administration (all AEs). Related AEs and SAEs will be followed up until 17 weeks after end of treatment.

  2. Multiplex immunohistochemistry assay to gain insight into the composition of immune cell subsets

    To analyze the immunological composition in tumor biopsies using an established immunohistochemistry (IHC) assay for the detection of CD3, CD8, FoxP3, CD45RO and CD20 positive cells; these results will support the decision on the RP2D as part of the planned trial.

    Measured: At baseline and at the end of Cycle 3 (each cycle is 21 days)

Secondary outcomes (2)

  1. Recommended Phase 2 Dose (RP2D)

    To determine the Recommended Phase 2 Dose (RP2D) of PRECIOUS-01 for a subsequent Phase II trial.

    Measured: From enrollment up to and including 21 days after last PRECIOUS-01 administration. Side effects will be followed up until 17 weeks after end of treatment.

  2. Immunological responses in blood

    Occurrence and magnitude of functional responses of iNKT cells and T cells will be studied. Serum cytokine levels will be determined by cytokine bead array. T cell specificity will be tested by multimer analysis. DC, iNKT cell, and NK cell activation status and functionality studies (cytokine responses) by flowcytometry. PAXgene blood will be collected before and 24 hours after every IMP administration. mRNA levels for IFN-related genes will be determined by qPCR. Anti-NY-ESO-1 antibodies will be studied.

    Measured: From study initiation up to and including the database lock, which is estimated to be 24 months later

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Feb 2021
  2. Study start11 Jan 2021
  3. Primary completionDec 2026 (estimated)
  4. Study completionDec 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Sequential
Model description
Eligible subjects will receive three i.v. infusions of PRECIOUS-01 at a 3-weekly interval in three dose-finding cohorts (low: 0.4 mg/kg, intermediate: 0.8 mg/kg, and high: 1.6 mg/kg fixed doses). Subjects will be monitored for safety and the occurrence of Dose-Limiting Toxicities (DLTs). A 3+3 design is used for the dose escalation steps. Three subjects will be enrolled sequentially per cohort. If the maximum tolerated dose (MTD) is not reached in the planned dose escalation cohorts, the RP2D will be based on the observed safety and immune modulatory activity as pharmacodynamic parameter supporting the RP2D. The sample size is based on the determination of the MTD/RP2D. In order to collect sufficient information regarding changes in immune related parameters as readout for pharmacodynamics of the particles, it is planned to extend the two highest dosing cohorts to a total of six subjects or to extend the highest dosing cohort to a total of nine subjects, depending on observed toxicity.
Masking
None (open label)
Enrolment
15 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04751786
Sponsor's protocol ID
NL 72876.091.20
Other IDs
2017-002568-41, 2017
Acronym
PRECIOUS-01
Status last verified
Aug 2026
First submitted
11 Dec 2020
Last updated
31 Aug 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: Individual participant data will be listed by measure and time point.

Publications

  • Dolen Y, Kreutz M, Gileadi U, Tel J, Vasaturo A, van Dinther EA, van Hout-Kuijer MA, Cerundolo V, Figdor CG. Co-delivery of PLGA encapsulated invariant NKT cell agonist with antigenic protein induce strong T cell-mediated antitumor immune responses. Oncoimmunology. 2015 Aug 12;5(1):e1068493. doi: 10.1080/2162402X.2015.1068493. eCollection 2016.

    PubMed 26942088

  • Creemers JHA, Pawlitzky I, Grosios K, Gileadi U, Middleton MR, Gerritsen WR, Mehra N, Rivoltini L, Walters I, Figdor CG, Ottevanger PB, de Vries IJM. Assessing the safety, tolerability and efficacy of PLGA-based immunomodulatory nanoparticles in patients with advanced NY-ESO-1-positive cancers: a first-in-human phase I open-label dose-escalation study protocol. BMJ Open. 2021 Nov 30;11(11):e050725. doi: 10.1136/bmjopen-2021-050725.

    PubMed 34848513

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing PRECIOUS-01 in people with Advanced Solid Tumor, run by Radboud University Medical Center at 1 site in Netherlands.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 19 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 31 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety of PRECIOUS-01 (time frame: From enrollment up to and including 21 days after last PRECIOUS-01 administration (all AEs). Related AEs and SAEs will be followed up until 17 weeks after end of treatment.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04751786, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Aug 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in