[68Ga]Ga-PentixaFor-PET imaging for staging of marginal zone lymphoma

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Pentixapharm AG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04], Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Diagnosis [E01]

Trial duration

20 May 2024 → 6 Jun 2025

Decision date (initial)

2023-11-30

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

PentixaPharm GmbH

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Diagnosis, Efficacy, Safety

1. To assess the superiority in terms of sensitivity and non-inferiority in terms of specificity of [68Ga]Ga-PTF PET/CT imaging vs. [18F]FDG PET/CT imaging in tumor detection on a lesion-basis confirmed by a Standard of Truth (SoT; centrally histopathological confirmation of tumor tissue) or surrogate SoT (central evaluation clinical and imaging follow-up).

Secondary objectives 16

1. 3.To assess the impact on staging of each PET/CT ([68Ga]Ga-PTF and [18F]FDG) imaging agent on a patient-basis locally by referring physicians
2. 4.To assess the impact on the intended treatment plan and patient management of each PET/CT imaging agent on a patient-basis locally by referring physicians and centrally by an Independent Committee.
3. 2. To assess the impact on staging of each PET/CT imaging agent on a patient-basis centrally by an Independent Committee
4. 5. To assess the inter-observer agreement of local and central assessment in terms of staging
5. 6. To assess the impact on staging of each PET/CT imaging agent on a patient-basis, locally by referring physicians and centrally by an Independent Committee, stratified in MZL subtypes (nodal, extranodal, splenic)
6. 7. To assess the impact on the intended treatment plan and patient management of each PET/CT imaging agent on a patient-basis, locally by referring physicians and centrally by an Independent Committee, stratified in MZL subtypes (nodal, extranodal, splenic)
7. 8. To centrally assess the diagnostic performance, consisting of sensitivity and specificity, of each PET/CT imaging agent in tumor detection on a region-basis (oral cavity/oropharynx, salivary glands, nasopharynx, stomach, small intestine, colon/rectum, lung, liver, spleen, skin, soft tissue including heart, breast, kidney/renal pelvis, bladder, eye/adnexa (orbit, conjunctiva, and eyelids), thyroid, central nervous system (CNS), bone, and the lymph node basins: cervical, axillary, mediastinum, pulmonary hilar, retroperitoneum, mesenteric, pelvic and inguinal, and bone marrow) confirmed by SoT or surrogate SoT.
8. 9. To assess the sensitivity of each PET/CT imaging agent in tumor detection on a patient-basis confirmed by SoT or surrogate SoT
9. 10. To assess the diagnostic accuracy, of each PET/CT imaging agent in tumor detection on a patient-basis and lesion-basis confirmed by SoT or surrogate SoT
10. 11. To determine the positive and negative predictive values (PPV, NPV) of each PET/CT imaging agent to detect tumor on a patient-basis and lesion-basis
11. 12. To determine the detection rate of each PET/CT imaging agent to detect tumor on a patient-basis and lesion-basis confirmed by SoT or surrogate SoT
12. 13. To determine the proportion of patients with additional or less tumoral lesions detected by [68Ga]Ga-PTF PET/CT imaging compared to [18F]FDG PET/CT imaging
13. 14. To assess the inter-reader and intra-reader agreement for tumor detection of each PET/CT imaging agent on a lesion-basis, region-basis and patient-basis.
14. 15. To evaluate reproducibility of [68Ga]Ga-PTF PET/CT imaging (reproducibility group)
15. 16. To assess the image quality of each PET/CT imaging agent
16. 17. To evaluate the safety and tolerability of each PET/CT imaging agent

Conditions and MedDRA coding

Marginal Zone Lymphoma

Study design 1 period

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration, European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-003408-PIP01-23

Plan to share IPD

No

IPD plan description

N/A

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. 1. Signed informed consent form (ICF) from the patient
2. 2. Patients of either gender, aged ≥ 18 years
3. 3. Patients with a histologically proven diagnosis of MZL according to the 4th revised edition of the World Health Organization HAEM4R classification of lymphoid neoplasms as well as established MZL stage. Patients must have a biopsy-proven nodal, extranodal, or splenic MZL (at the time of enrolment, the CXCR4 expression status will be unknown). The biopsy used for MZL diagnosis (diagnostic biopsy) must not be collected more than 12 weeks before Visit 1.
4. 4. Treatment-naïve
5. 5. Negative pregnancy test in women capable of child-bearing and their agreement to use highly effective contraception for 1 month after the last dose of [68Ga]Ga-PTF and [18F]FDG
6. 6. For male patients whose partner is of child-bearing potential: The patient is willing to ensure that he and his partner use effective contraception for 1 month after the last dose of [68Ga]Ga-PTF and [18F]FDG
7. 7. Acceptable organ function (refer to Protocol for complete information)
8. 8. Life expectancy ≥ 12 weeks as estimated by the Investigator
9. 9. The patient must not have undergone any physical or pharmacological intervention with curative or palliative intent between the time of any of the diagnostic measures and the [68Ga]Ga-PTF PET/CT and [18F]FDG PET/CT scan

Exclusion criteria 15

1. 1. Known hypersensitivity to any active pharmaceutical agent or constituent of the [68Ga]Ga-PTF and/or [18F]FDG product
2. 14. Body weight of less than 48 kg
3. 2. Inability to lie still for the entire imaging time
4. 3. Any severe acute or active chronic infection, as judged by the Investigator, at the time of screening or within two months prior to screening that may interfere with the diagnostic properties of [68Ga]Ga-PTF PET/CT or [18F]FDG PET/CT imaging
5. 4. Patients with plasma glucose levels higher than 11 mmol/L or 200 mg/dL prior [18F]FDG administration.
6. 5. Administration of any anticancer therapy within 1 month prior to study entry.
7. 6. Patients with complete resection of the tumor lesion(s)
8. 15. Any other concurrently active neoplasia, or other disease who could jeopardize study safety or data.
9. 7. Administration of another investigational medicinal product within 30 days or within 5 terminal elimination half-lives of a previous investigational medicinal product, whichever is longer, prior to study entry
10. 8. Current greater than grade 2 toxicity from any reason, per US-NCI "Common Terminology Criteria for Adverse Events v5.0" (NCI CTCAE 2017) except if tumor-related
11. 9. Pregnant or breast-feeding women.
12. 11. Colony-stimulating factor (CSF) therapy within 5 days prior to [18F]FDG PET/CT examination.
13. 12. Any recent myocardial infarction, stroke, or osteomyelitis within two months prior screening.
14. 10. Concomitant prohibited treatment which may interfere with [68Ga]Ga-PTF PET/CT imaging (systemic corticosteroids) administered within the last 1 month prior to study start
15. 13. Judged by the referring physician as not mentally or as not physically fit to understand and comply with protocol-related interventions and procedures (e.g., medically retarded, body weight > 180 kg for PET scanner)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 1. Superiority in terms of sensitivity and non-inferiority in terms of specificity of [68Ga]Ga-PTF PET/CT imaging vs. [18F]FDG PET/CT imaging in tumor detection on a lesion-basis confirmed by SoT (central histopathological confirmation of tumor tissue) or surrogate SoT (central evaluation of clinical and imaging follow-up). (Refer to Protocol for complete information)

Secondary endpoints 16

1. 3. Assessment of the impact on staging of each PET/CT imaging agent.
2. 4. Assessment of the impact on the intended treatment plan and patient management of each PET/CT imaging agent.
3. 2. Central assessment of the impact on staging of each PET/CT imaging agent.
4. 5. Assessment of the percentage of inter-observer agreement of each PET/CT imaging agent local vs. central in terms of staging.
5. 6. Local and central assessment of the impact on staging of each PET/CT imaging agent and stratification in MZL subtypes.
6. 7. Local and central assessment of the impact on the intended treatment plan and patient management of each PET/CT imaging agent and stratification in MZL subtypes.
7. 8. Central assessment of diagnostic performance, consisting of sensitivity and specificity of each PET/CT imaging agent in tumor detection on a region-basis confirmed by SoT.
8. 9. Assessment of sensitivity of each PET/CT imaging agent in tumor detection on a patient-basis confirmed by SoT.
9. 10. Assessment of diagnostic accuracy of each PET/CT imaging agent to detect tumor lesions on a per patient-basis and lesion-basis confirmed by SoT.
10. 11. Determination of PPV and NPV of each PET/CT imaging agent to detect tumor on a patient-basis and lesion-basis.
11. 12. Tumor detection rate of each PET/CT imaging agent on a patient-basis and on lesion-basis confirmed by SoT or surrogate SoT.
12. 13. Proportion of patients with additional or less lesions detected by [68Ga]Ga-PTF PET/CT imaging compared to [18F]FDG PET/CT imaging.
13. 14. Assessment of the percentage of intra- and inter-reader agreement of each PET/CT imaging agent for tumor detection on a lesion-basis, region-basis and patient-basis.
14. 15. Evaluation of reproducibility of [68Ga]Ga-PTF PET/CT imaging by comparison of two successive [68Ga]Ga-PTF PET/CT scans in a subpopulation of patients.
15. 16. Assessment of the image quality of each PET/CT imaging agent in PET-positive lesions.
16. 17. To evaluate the safety and tolerability of each PET/CT imaging agent.

Investigational products

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

Test 1

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Pentixapharm AG

Sponsor organisation

Pentixapharm AG

Address

Bismarckstrasse 13, Altstadt Altstadt

City

Wuerzburg

Postcode

97080

Country

Germany

Scientific contact point

Organisation

Pentixapharm GmbH

Contact name

Clinical trial team

Public contact point

Organisation

Pentixapharm GmbH

Contact name

Clinical trial team

Third parties 4

Locations

5 EU/EEA countries · 20 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

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 33 files

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

Application history

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