Clinical trial NCT04029181: ImmunoPET With an Anti-CD8 Imaging Agent
Official title: ImmunoPET Imaging With ZED88082A in Patients Before and During Treatment With 1) MPDL3280A or 2) PD-1 Antibody Plus or Minus Ipilimumab
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Metastatic Cancer
Unresectable Malignant Neoplasm
Lead sponsor: University Medical Center Groningen
Sponsor class: OTHER
First posted: 2019-07-23
Enrollment: 47
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: This is a single-center, single-arm, investigator sponsored trial designed to evaluate the PK of the anti-CD8 imaging agent in patients prior to and during treatment with checkpoint inhibitors.


Eligibility criteria: Inclusion Criteria:

1. Subjects with histologically confirmed locally advanced or metastatic cancer for the following tumor types

   * Cancer types other than melanoma; subjects meeting the eligibility criteria as formulated in the MPDL3280A treatment study protocol (MPDL3280A-treatment-IST-UMCG) are eligible for part A or part B1.
   * Melanoma; subjects eligible to receive standard of care anti-PD1 therapy plus or minus ipilimumab, are eligible for part B2.
2. Tumor lesion(s) of which a histological biopsy can safely be obtained according to standard clinical care procedures.
3. Measurable disease, as defined by standard RECIST v1.1. Previously irradiated lesions should not be counted as target lesions.
4. Signed informed consent.
5. Age ≥18 at the time of signing informed consent.
6. Life expectancy ≥12 weeks.
7. Eastern Cooperative Oncology Group (ECOG) performance status 0-1
8. Ability to comply with the protocol.
9. For female patients of childbearing potential and male patients with partners of childbearing potential, agreement (by patient and/or partner) to use a highly effective form(s) of contraception (i.e., one that results in a low failure rate \[\< 1% per year\] when used consistently and correctly).

Exclusion Criteria:

1. Potential subjects with cancer other than melanoma will be excluded from participation in this study if they meet exclusion criteria formulated in the MPDL3280A treatment study protocol (MPDL3280A-treatment-IST-UMCG).
2. Signs or symptoms of infection within 2 weeks prior to anti-CD8 imaging agent injection.
3. Prior immune checkpoint inhibitor treatment, including but not limited to anti-PD1 and anti-PD-L1 therapeutic antibodies.
4. History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
5. 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 the anti-CD8 imaging agent, or that may affect the interpretation of the results or render the patient at high risk from complications.
6. Pregnant or lactating women.

Primary outcomes:
measure: Incidence of adverse events related to tracer administration as assessed by CTCAE v4.0
timeFrame: 2 years
measure: Appropriate dosing of anti-CD8 imaging agent and PET imaging time points
timeFrame: 2 years
measure: Pharmacokinetics (PK) of anti-CD8 imaging agent
timeFrame: 2 years
measure: Immunogenic potential of the anti-CD8 imaging agent by measuring incidence of anti-drug antibodies
timeFrame: 2 years
Secondary outcomes:
measure: Heterogeneity of tumor uptake of the anti-CD8 imaging agent
timeFrame: 2 years
measure: Correlation of normal organ uptake of the anti-CD8 imaging agent to (serious) adverse events (possibly) related to immune checkpoint inhibitor treatment
timeFrame: 2 years
measure: Correlation of tumor uptake of the anti-CD8 imaging agent and immune cell CD8 expression
timeFrame: 2 years
measure: Correlation of anti-CD8 imaging agent normal tissue kinetics with blood kinetics
timeFrame: 2 years
measure: Dosimetry
timeFrame: 2 years
Other outcomes:
Locations:
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
Study officials:
affiliation: University Medical Center Groningen
name: E. G.E. de Vries, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ogasawara A, Kiefer JR, Gill H, Chiang E, Sriraman S, Ferl GZ, Ziai J, Bohorquez SS, Guelman S, Wang X, Yang J, Phan MM, Nguyen V, Chung S, Yu C, Tinianow J, Waaijer SJH, De Crespigny A, Marik J, Boswell CA, Zabka T, Staflin K, Williams SP. Preclinical development of ZED8, an 89Zr immuno-PET reagent for monitoring tumor CD8 status in patients undergoing cancer immunotherapy. Eur J Nucl Med Mol Imaging. 2023 Jan;50(2):287-301. doi: 10.1007/s00259-022-05968-6. Epub 2022 Oct 22.