Immuno-positron Emission Tomography Study of 89Zr-S095012 in Patients With Advanced Solid Tumours

Study Overview
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Brief Summary
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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)

Official Title
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An Open Label, Multicentre, Positron Emission Tomography (PET) Imaging Study Using Zirconium-89 to Investigate the Biodistribution and Tumour Uptake of a PD-L1x4-1BB Bispecific Antibody (S095012) in Patients With Advanced Solid Tumours

Conditions
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Advanced Solid Tumor

Intervention / Treatment
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* Drug: 89Zr-S095012 tracer and S095012 will be administered via an IV infusion


Participation Criteria
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Eligibility Criteria
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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 metastasis) Adequate organ function as assessed by laboratory tests (especially adequate hepatic function) Serologic testing for cytomegalovirus (CMV) and Epstein-Barr virus (EBV) must show absence of IgM antibodies against CMV and EBV-VCA (Viral Capsid Antigen) 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 89Zr-S095012 tracer with S095012<br> | Drug: 89Zr-S095012 tracer and S095012 will be administered via an IV infusion<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in PET/CT scan images | Visual analysis of target lesions | Within 14 days following the tracer injection and baseline (before the first treatment administration (during the dose range finding period)) | 
| Change in PET/CT scan images | Visual analysis of target lesions | Within 14 days following the tracer injection and baseline (before the first treatment administration) | 
| PET/CT scan images | Visual analysis of target lesions | Up to 8 days following the first treatment administration | 
| Parameters derived from PET scans for organs and tumour lesions | Change in Volume of interest | Within 14 days following the tracer injection and baseline (before the first treatment administration (during the dose range finding period)) | 
| Parameters derived from PET scans for organs and tumour lesions | Change in Volume of interest | Within 14 days following the tracer injection and baseline (before the first treatment administration) | 
| Parameters derived from PET scans for organs and tumour lesions | Volume of interest | Up to 8 days following first treatment administration | 
| Parameters derived from PET scan images to assess uptake in tumour lesions and normal tissues | Change in Standardised uptake value (SUV) | Within 14 days following the tracer injection and baseline (before the first treatment administration (during the dose range finding period)) | 
| Parameters derived from PET scan images to assess uptake in tumour lesions and normal tissues | Change in Standardised uptake value (SUV) | Within 14 days following the tracer injection and baseline ( before the first treatment administration) | 
| Parameters derived from PET scan images to assess uptake in tumour lesions and normal tissues | Standardised uptake value (SUV) | Up to 8 days following first treatment administration | 
| Serum PK parameters of 89Zr-S095012 during the range finding period (Part A) | Area under the curve (AUC) | 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) | 
| Serum PK parameters of 89Zr-S095012 at baseline (Part B) | Area under the curve (AUC) | 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 | 
| Serum PK parameters of 89Zr-S095012 on treatment (Part C- schedule 1) | Area under the curve (AUC) | 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 | 
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum PK parameters of S095012 during the range finding period (Part A) | Area under the curve (AUC) | 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) | 
| Serum PK parameters of S095012 at baseline (Part B) | Area under the curve (AUC) | 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 | 
| Serum PK parameters of S095012 on treatment (Part C - schedule 1) | Area under the curve (AUC) | 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 | 
| Organ and whole-body radiation exposure (milliSievert 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 | 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) | 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). |