Clinical trial

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

Name

CL1-95012-002

Description

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)

Trial arms

Trial start

2022-11-21

Estimated PCD

2025-06-12

Trial end

2025-09-30

Status

Recruiting

Phase

Early phase I

Treatment

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.

Arms:

89Zr-S095012 tracer with S095012

Size

Primary endpoint

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))

Change in PET/CT scan images

Within 14 days following the tracer injection and baseline (before the first treatment administration)

PET/CT scan images

Up to 8 days following the first treatment administration

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))

Parameters derived from PET scans for organs and tumour lesions

Within 14 days following the tracer injection and baseline (before the first treatment administration)

Parameters derived from PET scans for organs and tumour lesions

Up to 8 days following first treatment administration

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))

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)

Parameters derived from PET scan images to assess uptake in tumour lesions and normal tissues

Up to 8 days following first treatment administration

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)

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

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

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

Eligibility criteria

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.

Protocol

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE1'], 'designInfo': {'allocation': 'NA', 'interventionModel': 'SINGLE_GROUP', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 33, 'type': 'ESTIMATED'}}

Updated at

2024-04-25

1 organization

1 product

1 indication

Organization

Institut de Recherches Internationales Servier

Product

89Zr-S095012

Indication

Advanced Solid Tumor