advanced solid tumors
Conditions
Interventions
For the Imaging Study, once or twice, depending on the group the patient is
participating in, a radioactive tracer 89-ZrS95012 +- a mass dose of the Study
drug S95012 will be administered, followed
Sponsors
Servier R&D Benelux
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Men and women of >= 18 years of age on the day the consent is signed. 2. Participants with histologically confirmed diagnosis of unresectable, locally advanced or metastatic solid tumor for which standard treatment options are not available, no longer effective, or not tolerated. Participant should have a documented disease progression on prior therapy before entry into this study. 3. Participants must have at least one measurable target lesion as per RECIST 1.1. 4. ECOG performance status of 0 or 1 5. For participants in part B/C (optional for part A): Participant with no available archived material must have one or more tumor lesions amenable to biopsy. Baseline biopsies are not mandatory if archived tumor biopsy specimens collected no later than 9 months before screening, are available. If no archived material is available, a fresh biopsy must be collected at baseline. 6. Adequate organ function as assessed by laboratory tests within 72 hours prior to the first IMP administration: - Absolute neutrophil count (ANC) >= 1500/µL. - Platelet count >= 75 000/µL (this criterion must be met without transfusion and thrombopoietin for at least two weeks prior to IMP administration). - Haemoglobin >= 8 g/dL (this criterion must not be met with the use of transfusion and erythropoietin for at least two weeks prior to IMP administration). - Glomerular filtration rate (GFR) or measured or calculated creatinine clearance (CrCl) >= 30 mL/min using the Cockcroft and Gault formula. Alternatively, the GFR can be estimated using the Modification of Diet in Renal Disease (MDRD) formula. However, the estimation of CrCl must be done using the same methodology for a given participant (see Appendix 5). - Total bilirubin = 3 g/dL 7. Woman must use a highly effective method of birth control during study treatment and until 120 days after last dose of IMP In case of use of oral contraception, women should have been stable on the same contraceptive drug (same active principle) for at least 6 months prior to the first IMP administration. 8. A male participant with childbearing potential partners must use a condom during the study and until at least 120 days after the last dose of IMP. Participants that are sterile or vasectomised must use a condom during sexual intercourse with a childbearing potential partner in order to avid exposure of an existing embryo/foetus. In addition, contraception should be considered for their female partner. Contraceptive measures do not apply if the participant is sterile, vasectomized or sexual abstinent. Sperm donation will not be allowed during the study and for 120 days after the last dose of IMP. 9. Human immunodeficiency virus (HIV)-infected participants must have well-controlled HIV or be on adequate antiretroviral therapy defined as: CD4 lymphocyte count > 350 cells/µL at time of screening. Achieving and maintaining virologic suppression defined as confirmed HIV ribonucleic acid (RNA) level below 50 or lower limit of detection by the local available assay at time of screening and for at least 12 weeks prior to screening.
Exclusion criteria
Exclusion criteria: 11. Pregnant and lactating women. 12. Unlikely to cooperate in the study. 13. Participation in another interventional study at the same time; participation in non-interventional registries or epidemiological studies is allowed. 14. Participant already included in the study (informed consent signed). 15. Participants with previously treated brain metastases may participate provided they are radiologically stable, clinically asymptomatic and are off immunosuppressive therapies for at least 4 weeks. Low dose of steroid = 3 immune-related pneumonitis, colitis, hepatitis, myocarditis. 24. Participants receiving systemic steroids at a dose of more than 10 mg per day equivalent of prednisone. Ocular, inhaled, intranasal, topical steroids are allowed. Local steroid injections (intra-articular and/or epidural) are allowed as a palliative therapeutic option only. 25. Participants who have received an allogenic solid organ or bone marrow transplant. 26. Participants with a history of interstitial lung disease, pneumonitis requiring systemic steroids for treatment, or current pneumonitis. 27. Participants with a clinically significant cardiovascular disease or condition, including: a. New York Heart Association classification III or IV, known symptomatic coronary artery disease, or symptoms of coronary artery disease on systems review, or known cardiac arrhy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Visual analysis of PET/CT scan images. Quantitative parameters derived from PET scans for blood pool, organs and tumor lesions (time-uptake curves, tumor to background ratio, *). - Quantitative parameters derived from PET scan images to assess uptake in tumor lesions and normal tissues reported with standardised uptake value (SUV) and concentration for each volume of interest (VOI). Serum PK parameters of 89Zr*S095012. Comparison of 89Zr*S095012 tumor uptake (as described using SUV and concentrations) before and on treatment with different doses of S095012. - Incidence and severity of adverse events (AEs). Discontinuing study intervention due to an AE. | — |
Secondary
| Measure | Time frame |
|---|---|
| Serum PK parameters of S095012. -Organ and whole-body radiation exposure (mSv per Mega Becquerel (MBq): Highest absorbed dose, specific absorbed dose to the target lesions, absorbed dose per organ and cumulative absorbed organ doses. -Assessment based on Response Evaluation Criteria in Solid Tumors (RECIST) V1.1, objective response rate (ORR). | — |
Countries
Netherlands
Outcome results
None listed