Molecular PD-L1 PET/CT Imaging with 89Zr-atezolizumab to Monitor Immune Responses in metastatic Triple Negative Breast Cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Karolinska University Hospital

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

1 Feb 2023 → 23 Dec 2024

Decision date (initial)

2022-12-05

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Swedish Cancer Society

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

To establish the statistical agreement (by means of Cohen’s kappa coefficient) between PD-L1 status by the experimental method (PET/CT with 89Zr-atezolizumab) and the current reference standard (IHC on a tumour biopsy or resection specimen).

Secondary objectives 5

1. Evaluate the therapy-predictive value of 89Zr-atezolizumab PET/CT, compared to the current reference standard (PD-L1 IHC) for treatment with nab-paclitaxel, carboplatin + atezolizumab.
2. Treatment outcomes (progression free survival, disease response rate, treatment discontinuation rates) will be compared in three patient groups: 1) IHC positive and PET positive, 2) IHC positive and PET negative, 3) IHC negative and PET positive.
3. Investigate inter- and intra-lesional differences in PD-L1 positivity by 89Zr-atezolizumab radiotracer uptake.
4. Investigate the therapeutic role of atezolizumab for ER-low, PD-L1 positive breast cancer (ER expression 1-10%).
5. Investigate the possible role of 89Zr-atezolizumab PET/CT as a method of detecting otherwise (with regular CT-chest-abdomen) occult metastatic sites including sanctuary sites such as the central nervous system (CNS).

Conditions and MedDRA coding

Metastatic triple negative breast cancer

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Patients with metastatic triple-negative breast cancer by pathological criteria: oestrogen receptor expression <10%, progesterone receptor (PR) expression <10%, HER2 negative, on the primary tumour or a metastatic biopsy
2. Measurable disease according to RECIST v1.1.
3. At least one metastatic lesion accessible for biopsy.
4. Deemed by treating physician as fit for systemic therapy according to study protocol.
5. ECOG performance score 0 or 1.
6. Age >18 years old.
7. Adequate bone marrow, renal and hepatic functions.
8. Able and willing to provide written informed consent

Exclusion criteria 10

1. Contraindications for PET/CT as defined for clinical practice.
2. Other malignancy diagnosed within the last five years.
3. Patients in child-bearing age without adequate contraception.
4. Pregnancy or lactation.
5. Uncontrolled hypertension, heart-, liver-, or kidney-diseases or other medical/psychiatric disorders.
6. History of autoimmune disease.
7. Vaccination with a live vaccine within 30 days of the first dose of study treatment
8. A known history of HIV infection, hepatitis B or hepatitis C infection or active tuberculosis.
9. Treatment with systemic corticosteroids or other systemic immunosuppressive medications within 2 weeks prior to randomisation.
10. Hypersensitivity to atezolizumab.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Level of statistical agreement by means of Cohen’s kappa coefficient between PD-L1 IHC (positive defined as expression ≥1% on immune cells with SP142) and PD-L1 PET/CT (PD-L1 positivity is defined as having at least one lesion with radiotracer uptake over the background uptake).

Secondary endpoints 4

1. Progression free survival, disease response rate and treatment discontinuation rates in three patient groups: 1. IHC positive and PET positive; 2. IHC positive and PET negative; 3. IHC negative and PET positive.
2. Discordance in 89Zr-atezolizumab between different sites and within metastatic sites in the body.
3. Progression free survival, disease response rate and treatment discontinuation rates in patients with ER-low mBC treated with nab-paclitaxel, carboplatin and atezolizumab.
4. Percentage of 89Zr-atezolizumab uptake in sites, not previously determined on the routine radiological investigation with CT, as a measure of cancer spread determined on whole body 89Zr-atezolizumab PET/CT in and different metastases.

Investigational products

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

Test 2

Auxiliary 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Karolinska University Hospital

Sponsor organisation

Karolinska University Hospital

Address

Eugeniavagen 3

City

Solna

Postcode

171 64

Country

Sweden

Scientific contact point

Organisation

Karolinska University Hospital

Contact name

Coordinating investigator

Public contact point

Organisation

Karolinska University Hospital

Contact name

Coordinating investigator

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 1 file

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