PD-L1 PET imaging during CAR T-cell therapy

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Universitair Medisch Centrum Groningen

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

20 May 2026 → 20 May 2026

Decision date (initial)

2024-11-20

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-518422-32-01

EudraCT number

2021-005192-39

ClinicalTrials.gov

NCT05404048

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Diagnosis

To study the expression of PD-L1 in normal tissue and lymphoma lesions before CD19-directed CAR T-cell therapy in LBCL patients by 89Zr-atezolizumab PET/CT imaging and to correlate pretreatment 89Zr-atezolizumab uptake to the response to CD19-directed CAR T-cell therapy and thereby identify clinically relevant PD-L1 expression.

To study whether the amount of 89Zr-atezolizumab uptake, measured by the intensity of 89Zr-atezolizumab PET/CT imaging (SUV), can be used to differentiate lymphoma activity and treatment-related inflammatory signal (histiocytic/sarcoid-like reaction) in patients with an end-of-treatment 18F-FDG-positive PET/CT signal.

Secondary objectives 5

1. To correlate the pretreatment 89Zr-atezolizumab distribution to CAR T-cell peak expansion and persistence
2. To correlate the pretreatment 89Zr-atezolizumab uptake to CAR T-cell therapy related grade 1-5 adverse events (cytokine release syndrome (CRS) and immune effector cell associated neurotoxicity (ICANS))
3. To correlate tumor 89Zr-atezolizumab uptake with tumor and immune cell PD-L1-expression as assessed by immunohistochemistry on a fresh contemporaneous tumor biopsy
4. To compare the 89Zr-atezolizumab distribution in irradiated versus non-irradiated lymphoma lesions in patients who require radiotherapy as a bridging strategy prior to CAR Tcell infusion. If possible, these results will be compared to tumor and immune cell PD-L1 expression as assessed by immunohistochemistry on a fresh contemporaneous tumor biopsy of an irradiated lymphoma lesion
5. To determine the incidence of a treatment-related inflammatory signal on 18F-FDG-PET/CT scan (histiocytic/sarcoid-like reaction) after CAR T-cell therapy

Conditions and MedDRA coding

(Diffuse) Large B-cell Lymphoma

Study design 1 period

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Histologically confirmed DLBCL and associated subtypes, defined by WHO 2016 classification: DLBCL not otherwise specified (NOS), High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements with DLBCL histology (DHL/THL) and FL3B, Aggressive B-cell lymphoma, T-cell/histiocyte rich B-cell lymphoma, Primary mediastinal B-cell lymphoma, EBV+ DLBCL, transformed lymphoma (e.g. transformed follicular or marginal zone lymphoma)
2. Eligible for CAR T-cell therapy according to criteria set by the Dutch National Tumor Board
3. Measurable disease, as defined by Lugano criteria
4. Signed informed consent
5. Age ≥18 at the time of signing informed consent
6. Ability to comply with the protocol

Exclusion criteria 3

1. Signs or symptoms of active infection within 2 weeks prior to 89Zr-atezolizumab injection unless treated to resolution
2. History of severe allergic, anaphylactic or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
3. Any other diseases, metabolic dysfunction, physical examination finding or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of 89Zr-atezolizumab, or that may affect the interpretation of the results or render the patient at high risk from complications

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. to study the expression of PD-L1 in normal tissue and lymphoma lesions before CD19- directed CAR T-cell therapy in LBCL patients by 89Zr-atezolizumab PET/CT imaging and to correlate pretreatment 89Zr-atezolizumab uptake to response to CD19-directed CAR T-cell therapy and thereby identify clinically relevant PD-L1 expression. Heterogeneity of 89Zr-atezolizumab uptake will be evaluated by measuring standardized uptake value (SUV) on the 89Zr-atezolizumab PET/CT scan
2. To study whether the amount of 89Zr-atezolizumab uptake, measured by the intensity of 89Zr-atezolizumab PET/CT imaging (SUV), can be used to differentiate between lymphoma activity and treatment-related inflammatory reaction (histiocytic/sarcoidlike reaction) in patients with an end-of-treatment 18F-FDG-positive PET/CT signal

Secondary endpoints 5

1. To correlate the pretreatment 89Zr-atezolizumab distribution to CAR T-cell peak expansion and persistence
2. To correlate the pretreatment 89Zr-atezolizumab uptake to CAR T-cell therapy related grade 1-5 adverse events (cytokine release syndrome (CRS) and immune effector cell associated neurotoxicity syndrome (ICANS)).
3. To correlate tumor 89Zr-atezolizumab uptake with tumor and immune cell PD-L1 expression as assessed by immunohistochemistry on a fresh contemporaneous tumor biopsy
4. To compare the 89Zr-atezolizumab distribution in irradiated versus non-irradiated lymphoma lesions in patients who require radiotherapy as a bridging strategy prior to CAR T-cell infusion. If possible, these results will be compared to tumor and immune cell PD-L1 expression as assessed by immunohistochemistry on a fresh contemporaneous tumor biopsy of an irradiated lymphoma lesion
5. To determine the incidence of a treatment-related inflammatory signal on 18F-FDGPET/CT scan (histiocytic/sarcoid-like reaction) after CAR T-cell therapy

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Universitair Medisch Centrum Groningen

Sponsor organisation

Universitair Medisch Centrum Groningen

Address

Hanzeplein 1

City

Groningen

Postcode

9713 GZ

Country

Netherlands

Scientific contact point

Organisation

Universitair Medisch Centrum Groningen

Contact name

Janneke de Boer

Public contact point

Organisation

Universitair Medisch Centrum Groningen

Contact name

Janneke de Boer

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 4 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications