Advanced Solid Tumor
Conditions
Brief summary
The purpose of this study is to assess the whole-body biodistribution and tumour uptake of 89Zr-S095012 in participants with solid tumours treated with S095012 (PD-L1x4-1BB bispecific antibody)
Interventions
DRUG89Zr-S095012 tracer and S095012 will be administered via an IV infusion
Imaging period 1 (Part A and Part B): The tracer will be administered with S095012 at non-therapeutic mass dose. The optimal mass dose of S095012 will be investigated in part A, and used in part B. Treatment period (Part A to C): S095012 will be administered with multiple 28 days- cycles in a Q2W schedule. Imaging period 2 (Part C): A second tracer dose will be administered at 1st treatment dose of S095012 in part C.
Sponsors
Institut de Recherches Internationales Servier
ADIR, a Servier Group company
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed diagnosis of unresectable, locally advanced or metastatic solid tumour, for which standard treatment options are not available, no longer effective, or not tolerated * At least one measurable target lesion as per RECIST 1.1 * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * Royal Marsden Prognosis score of 0 to 1 (score based on lactate dehydrogenase (LDH) value, albumin value and number of sites of metastasis) * Adequate organ function as assessed by laboratory tests (especially adequate hepatic function) * Negative test results for cytomegalovirus (CMV), Epstein-Barr virus (EBV), Hepatitis B virus (HBV), and Hepatitis C virus (HCV) infection, according to local standards.
Exclusion criteria
* Participants with no available archived material and no tumour lesions amenable to biopsy * Participants with primary central nervous system malignancies, with Child-Pugh Class B8 or higher, or C liver cirrhosis * Participants with active auto-immune disease or immune-related adverse event currently requiring systemic anti-inflammatory agent (more than 10mg/day prednisone or equivalent) * Participants with a history of an opportunistic infection within a year before the administration of first study drug dose are excluded. * Participants who received either systemic corticosteroids (\> 10 mg per day of prednisone or equivalent) or other immunosuppressive medication during the 2 months prior to the first dose of the study drug are excluded. * Participants with prior history of Grade ≥ 3 immune-related pneumonitis, colitis, hepatitis, or myocarditis * Participants with a history of progressive multifocal leukoencephalopathy * Participants must not have a history of active tuberculosis requiring treatment within 3 years prior to the start of treatment or a suspicion of latent tuberculosis by the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in PET/CT scan images | Within 14 days following the tracer injection and baseline (before the first treatment administration (during the dose range finding period)) | Visual analysis of target lesions |
| PET/CT scan images | Up to 8 days following the first treatment administration | Visual analysis of target lesions |
| Parameters derived from PET scans for organs and tumour lesions | Within 14 days following the tracer injection and baseline (before the first treatment administration (during the dose range finding period)) | Change in Volume of interest |
| Parameters derived from PET scan images to assess uptake in tumour lesions and normal tissues | Within 14 days following the tracer injection and baseline (before the first treatment administration (during the dose range finding period)) | Change in Standardised uptake value (SUV) |
| Serum PK parameters of 89Zr-S095012 during the range finding period (Part A) | radioactive plasma samples taken at : 5, 30, 60, 120 minutes, 6 hours (on Day-14) and on Day-13, Day-12, Day-10 and Day-7 following the tracer injection and before the first treatment administration (during the dose ranging period) | Area under the curve (AUC) |
| Serum PK parameters of 89Zr-S095012 at baseline (Part B) | radioactive plasma samples taken at : 5, 30, 60, 120 minutes, 6 hours (on Day-14) and on Day-13, Day-12, Day-10 and Day-7 following the tracer injection and before the first treatment administration | Area under the curve (AUC) |
| Serum PK parameters of 89Zr-S095012 on treatment (Part C- schedule 1) | radioactive plasma samples taken at : 5, 30, 60, 120 minutes, 6 hours (on Day 1) and on Day 2, Day 3, Day 5 and Day 8 following the first treatment administration | Area under the curve (AUC) |
| Change in Comparison of 89Zr-S095012 tumour uptake (as described using Standardised Uptake Value and concentrations) before and on treatment with different doses of S095012. | In Part C (imaging period 2) between Day 1 and Day 8 of cycle 1 (the duration of cycle 1 is 28 days) | — |
| Incidence and severity of adverse events | Throughout the study up to 30 days after the last IMP for all AEs, or up to 90 days for all AEs related to the IMP and death | — |
| Number of patients discontinuing study intervention due to an adverse event | Throughout the study up to 30 days after the last IMP for all AEs, or up to 90 days for all AEs related to the IMP and death | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serum PK parameters of S095012 during the range finding period (Part A) | plasma samples taken at : 5, 30, 60, 120 minutes, 6 hours (on Day-14) and on Day-13, Day-12, Day-10 and Day-7 following the tracer injection and before the first treatment administration (during the dose ranging period) | Area under the curve (AUC) |
| Serum PK parameters of S095012 at baseline (Part B) | plasma samples taken at : 5, 30, 60, 120 minutes, 6 hours (on Day-14) and on Day-13, Day-12, Day-10 and Day-7 following the tracer injection and before the first treatment administration | Area under the curve (AUC) |
| Serum PK parameters of S095012 on treatment (Part C - schedule 1) | plasma samples taken at : 5, 30, 60, 120 minutes, 6 hours (on Day 1) and on Day 2, Day 3, Day 5, Day 8 and Day 15 following the first treatment administration | Area under the curve (AUC) |
| Organ and whole-body radiation exposure (milliSilvert per Mega Becquerel (mSv/MBq): Effective dose per organ and whole-body effective dose. | In Part A, B and C (imaging period 1) at Day-14 | — |
| Preliminary antitumour activity assessment of S95012 | The events to be studied are Complete Response or Partial Response, from the first treatment administration up to one year (for patients with confirmed Complete response) or 2 years (for Patients with confirmed Partial Response). | Percentage of patients who achieved complete response or partial response (ie, objective response rate (ORR)) according to Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1 (V1.1) |
Countries
Netherlands
Outcome results
None listed