ImmunoPET With an Anti-CD8 Imaging Agent

ImmunoPET Imaging With ZED88082A in Patients Before and During Treatment With 1) MPDL3280A or 2) PD-1 Antibody Plus or Minus Ipilimumab

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Metastatic Cancer; Unresectable Malignant Neoplasm
• Intervention / Treatment: Other: Anti-CD8 PET imaging agent

• Study Type: Interventional
• Enrollment (Actual): 47
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Netherlands
  • Groningen, Netherlands
    • University Medical Center Groningen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose finding cohort; In part A of this imaging trial, a dose finding study will be performed to establish safety, to assess the appropriate protein dose for PET-scanning and to assess the appropriate PET scanning interval.	Other: Anti-CD8 PET imaging agent; An imaging agent radiolabelled with 89Zr developed for in human PET imaging of CD8
Experimental: Feasibility cohort; The purpose of part B of the study is to analyze the PK of the anti-CD8 imaging agent in patients before and during treatment with checkpoint inhibitors.	Other: Anti-CD8 PET imaging agent; An imaging agent radiolabelled with 89Zr developed for in human PET imaging of CD8

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events related to tracer administration as assessed by CTCAE v4.0	Safety assessment through summaries of adverse events, changes in laboratory test results (if evaluation is indicated), changes in vital signs, and exposure to ZED88082A/CED88004S. Adverse event data will be recorded and summarized according to NCI CTCAE v4.0.	2 years
Appropriate dosing of anti-CD8 imaging agent and PET imaging time points	Appropriate dosing and imaging time points of the anti-CD8 imaging agent will be determined based on measurements of standardized uptake value (SUV) of defined volumes of interest (VOIs) on the immunoPET scan images	2 years
Pharmacokinetics (PK) of anti-CD8 imaging agent	Description of PK of the anti-CD8 imaging agent by measuring standardized uptake value (SUV) on PET scans performed 0, 2, 4 and/or 7 days after tracer injection before and during MPDL3280A or PD-1 antibody immune checkpoint inhibitor plus or minus ipilimumab treatment.	2 years
Immunogenic potential of the anti-CD8 imaging agent by measuring incidence of anti-drug antibodies	Assessment of the immunogenic potential of the anti-CD8 imaging agent by measuring incidence of anti-drug antibodies during the study relative to the prevalence of ADAs at baseline and assessing their relationship to other outcomes measured.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Heterogeneity of tumor uptake of the anti-CD8 imaging agent	Heterogeneity of imaging tracer uptake will be evaluated by measuring standardized uptake value (SUV) in defined volumes of interest (VOIs) of tumor lesions on the immunoPETscan images	2 years
Correlation of normal organ uptake of the anti-CD8 imaging agent to (serious) adverse events (possibly) related to immune checkpoint inhibitor treatment	Normal organ uptake of the anti-CD8 imaging agent as measured by SUVs on PET scan images will be analyzed on correlation to (serious) adverse events (possibly) related to ICI treatment, defined as all (S)AEs which are assessed as "possibly", "probably" or "definitely" related to ICI treatment.	2 years
Correlation of tumor uptake of the anti-CD8 imaging agent and immune cell CD8 expression	Results of immunohistochemical scoring of tumor and immune cell CD8 and other markers of lymphocytic infiltration in fresh biopsies will be described as a semi-quantitative score using the percentage of positive cells (continuous variable), intensity and pattern of staining (discrete variable). These IHC results will be compared with imaging tracer standardized uptake value (SUV) in defined volumes of interest (VOIs) of tumor lesions on the immunoPETscan images. Results of autoradiography will be described by measuring standardized uptake value (SUV) on the biopsy slides.	2 years
Correlation of anti-CD8 imaging agent normal tissue kinetics with blood kinetics	PK parameters will be derived from anti-CD8 imaging agent serum concentrations and will be summarized using descriptive statistics including but not limited to the number of patients, mean, standard deviation, median, minimum and maximum.	2 years
Dosimetry	Assessment of dosimetry will be performed by calculations of radioactivity in Bq or mSv of anti-CD8 imaging agent concentration in tumor target tissue, blood and other organs of interest with regards to injected dose (ID), derived from measurements of standardized uptake value (SUV) on immunoPET images and direct analysis of blood 89Zr-activity.	2 years

Collaborators and Investigators

• Sponsor: University Medical Center Groningen
• Investigators: Principal Investigator: E. G.E. de Vries, MD, PhD, University Medical Center Groningen

Publications and helpful links

General Publications

• 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. Erratum In: Eur J Nucl Med Mol Imaging. 2022 Nov 25;:

Study record dates

Study Major Dates

• Study Start (Actual): February 14, 2019
• Primary Completion (Actual): December 28, 2022
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: June 17, 2019
• First Submitted That Met QC Criteria: July 22, 2019
• First Posted (Actual): July 23, 2019

Study Record Updates

• Last Update Posted (Actual): May 3, 2024
• Last Update Submitted That Met QC Criteria: May 2, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: 201700848

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No