solid tumors
Conditions
Interventions
PRECIOUS-01 will be administered i.v. three times at 3-weekly intervals (Day 1,
Day 22 and Day 43).
Doses are specified as follows: low (0.4 mg/kg PRECIOUS-01), intermediate (0.8
mg/kg PRECIOUS-01)
Sponsors
Tumor Immunology
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Age >=18 years at time of signing informed consent. 2. Performance status (ECOG = 6 mmol/L; b. Absolute Lymphocyte Count (ALC) > 0.8 x 109/L; c. Absolute Neutrophil Count (ANC) >= 1.5 × 109/L; d. Platelet count > 100 x 109/L; e. Serum creatinine = 60 mL/min (as determined by MDRD [Modification of Diet in Renal Disease]) for patients with serum creatinine levels > 1.5 x ULN; f. Serum bilirubin
Exclusion criteria
Exclusion criteria: 1. 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, 2. 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] 3 months are allowed. 3. Subjects with thromboembolic events within the past year. 4. Subjects suffering from melanoma, non-Hodgkin lymphoma, or renal cell carcinoma who have a serum Lactic Acid Dehydrogenase (LDH) > ULN. 5. 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. 6. 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. 7. Concomitant use of oral or i.v. immunosuppressive drugs. Inhaled, topical or intranasal steroids and adrenal replacement steroids 150 mm Hg and/or diastolic > 100 mm Hg). 11. Serious (bleeding and clotting) condition(s) that may interfere with safe administration of PRECIOUS-01. 12. Abnormal or clinically significant coagulation parameters at the discretion of the Clinical Investigator, i.e.: a. Prothrombin Time - International Normalized Ratio (PT-INR) b. Activated Partial Thromboplastin Time (APTT) c. 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. 13. Evidence of any other conditions (such as psychological/familial sociological/geographical issues, psychiatric illness, infectious diseases, physical
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary endpoints of the trial are: - Safety profiles: incidence of treatment-emerging Adverse Events (AEs) and Serious Adverse Events (SAE), and laboratory abnormalities graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0 reporting severity and relatedness (see Appendix I); occurrence of DLTs; incidence of treatment discontinuations and treatment modifications due to AEs and laboratory abnormalities; changes in vital signs, electrocardiogram (ECG) and Eastern Cooperative Oncology Group performance status (ECOG PS); deaths; - The immune modulating effect directly in the tumor is planned to be assessed at baseline and after Cycle 3 specifically 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. | — |
Secondary
| Measure | Time frame |
|---|---|
| The secondary endpoints of the trial are: - The RP2D, which will be evaluated using all data on safety and the immune modulating effect per dose level tested (if MTD is reached at one of the tested dose levels, then this dose will be used) - Evaluation of the immune modulating activity at each dose level (focused on the presence of NY-ESO-1-specific T cells, iNKT cell activation, DC activation, cytokine responses, and anti-NY-ESO-1-specific antibody responses) using peripheral blood. | — |
Countries
Netherlands
Outcome results
None listed