NCT03313323: Zirconipi

Uptake and Biodistribution of 89Zirconium-labeled Ipilimumab in Ipilimumab Treated Patients With Metastatic Melanoma

Status unknown Phase 2 Last updated 15 April 2021

What this trial tests

Phase 2 trial testing 89Zirconium-labeled ipilimumab in Melanoma in 29 participants. Status unknown.

Timeline

16 February 2017

Primary endpoint
15 February 2022

15 February 2022

Quick facts

Lead sponsor	Amsterdam UMC, location VUmc
Phase	Phase 2
Status	Status unknown
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	diagnostic
Enrollment	29
Start date	16 February 2017
Primary completion	15 February 2022
Estimated completion	15 February 2022
Sites	1 location across Netherlands

Drugs / interventions tested

• 89Zirconium-labeled ipilimumab — full drug profile →

Conditions studied

• Melanoma — all drugs for Melanoma →

Sponsor

Amsterdam UMC, location VUmc — full company profile →

Who can join

18 and older, any sex, with Melanoma. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

Rationale:

Ipilimumab, a monoclonal antibody targeting CTLA-4, is approved for the treatment of metastatic melanoma and significantly increases median overall survival. However, use of this drug is associated with immune related adverse events (IRAEs) like colitis, hepatitis, dermatitis, alveolitis and hypophysitis in 10-40% of the patients. In general IRAEs are manageable by cessation of ipilimumab in combination with treatment with corticosteroids or TNF-alpha blockade but they can be severe or even life-threatening. In addition, treatment with ipilimumab is expensive. Because of the high costs and the potential serious toxicity of ipilimumab, it is of great importance to identify biomarkers that correlate with clinical activity and can be used to select patients that will benefit from CTLA-4 blockade therapy.

The investigators hypothesize that differences in response to treatment with ipilimumab are due to variability in the pharmacodynamics and -kinetics of the antibody. It is hypothesized that patients who do not respond to treatment with ipilimumab have lower drug levels in tumor tissues as compared to patients with a good response to therapy. In addition, the investigators hypothesize that IRAEs are associated with high drug levels in the affected tissue.

To visualize molecular interactions a novel technique is used in which positron emission tomography (PET) is combined with labeled monoclonal antibodies. Because ipilimumab induces activation of T-lymphocytes it is hypothesized that uptake of 89Zr-ipilimumab in tumor lesions and normal tissue is different (i.e. higher) after the second administration of ipilimumab (3 weeks after first injection). Therefore immuno-PET scans will be performed after the first and after the second injection of ipilimumab.

Objective:

Part one: The primary objective is:

1\. To assess uptake (visual and quantitative) of 89Zr-ipilimumab in tumor lesions and biodistribution at two timepoints (at start of ipilimumab therapy and after the second injection 3 weeks later).

The secondary objectives are:

1. To determine the correlation between tumor targeting of ipilimumab and response to therapy.
2. To assess uptake (visual and quantitative) of 89Zr-ipilimumab in normal tissues.
3. To determine de correlation between organ targeting and toxicity

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Biomarkers for Clinical Benefit of Immune Checkpoint Inhibitor Treatment-A Review From the Melanoma Perspective and Beyond.
   Buder-Bakhaya K, Hassel JC. · · 2018 · cited 166× · PMID 30002656 · DOI 10.3389/fimmu.2018.01474
2. Imaging of T-cells and their responses during anti-cancer immunotherapy.
   Krekorian M, Fruhwirth GO, Srinivas M, Figdor CG, et al · · 2019 · cited 79× · PMID 31656546 · DOI 10.7150/thno.37924
3. Molecular imaging biomarkers for immune checkpoint inhibitor therapy.
   van de Donk PP, Kist de Ruijter L, Lub-de Hooge MN, Brouwers AH, et al · · 2020 · cited 74× · PMID 32042331 · DOI 10.7150/thno.38339
4. ⁸⁹ Zr-ImmunoPET companion diagnostics and their impact in clinical drug development.
   McKnight BN, Viola-Villegas NT. · · 2018 · cited 41× · PMID 29341222 · DOI 10.1002/jlcr.3605
5. Aligning physics and physiology: Engineering antibodies for radionuclide delivery.
   Tsai WK, Wu AM. · · 2018 · cited 37× · PMID 29537104 · DOI 10.1002/jlcr.3622
6. ImmunoPET: Antibody-Based PET Imaging in Solid Tumors.
   Manafi-Farid R, Ataeinia B, Ranjbar S, Jamshidi Araghi Z, et al · · 2022 · cited 36× · PMID 35836956 · DOI 10.3389/fmed.2022.916693
7. Nanobodies as non-invasive imaging tools.
   Rashidian M, Ploegh H. · · 2020 · cited 35× · PMID 35754459 · DOI 10.1016/j.iotech.2020.07.001
8. Molecular imaging to support cancer immunotherapy.
   van de Donk PP, Oosting SF, Knapen DG, van der Wekken AJ, et al · · 2022 · cited 30× · PMID 35922089 · DOI 10.1136/jitc-2022-004949