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

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

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)

Study Overview

• Status: Recruiting
• Conditions: Advanced Solid Tumor
• Intervention / Treatment: Drug: 89Zr-S095012 tracer and S095012 will be administered via an IV infusion

• Study Type: Interventional
• Enrollment (Estimated): 33
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Institut de Recherches Internationales Servier Clinical Studies Department; Phone Number: +33155724366; Email: scientificinformation@servier.com

Study Locations

• Netherlands
  • Amsterdam, Netherlands, 1081 HZ
    • Not yet recruiting
    • Amsterdam UMC locatie VU - Medisch Centrum
  • Groningen, Netherlands, 9713 AZ
    • Recruiting
    • UMC Gronningen Oncologie

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 89Zr-S095012 tracer with S095012

Drug: 89Zr-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.

What is the study measuring?

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
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).
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

Collaborators and Investigators

• Sponsor: Institut de Recherches Internationales Servier
• Collaborators: ADIR, a Servier Group company

Publications and helpful links

Helpful Links

• Find Results on Servier Clinical Trial Data website

Study record dates

Study Major Dates

• Study Start (Actual): November 21, 2022
• Primary Completion (Estimated): June 12, 2025
• Study Completion (Estimated): September 30, 2025

Study Registration Dates

• First Submitted: October 28, 2022
• First Submitted That Met QC Criteria: December 5, 2022
• First Posted (Actual): December 6, 2022

Study Record Updates

• Last Update Posted (Actual): April 25, 2024
• Last Update Submitted That Met QC Criteria: April 23, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: CL1-95012-002; 2021-001764-20 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Qualified scientific and medical researchers can request access to anonymized patient-level and study-level clinical trial data.

Access can be requested for all interventional clinical studies:

• used for Marketing Authorization (MA) of medicines and new indications approved after 1 January 2014 in the European Economic Area (EEA) or the United States (US).
• where Servier is the Marketing Authorization Holder (MAH). The date of the first MA of the new medicine (or the new indication) in one of the EEA Member States will be considered for this scope.

In addition, access can be requested for all interventional clinical studies in patients:

• sponsored by Servier.
• with a first patient enrolled as of 1 January 2004 onwards.
• for New Chemical Entity or New Biological Entity (new pharmaceutical form excluded) for which development has been terminated before any Marketing authorization (MA) approval.

• IPD Sharing Time Frame: After Marketing Authorisation in EEA or US if the study is used for the approval.
• IPD Sharing Access Criteria: Researchers should register on Servier Data Portal and fill in the research proposal form. This form in four parts should be fully documented. The Research Proposal Form will not be reviewed until all mandatory fields are completed.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No