ImmunoPET With an Anti-CD8 Imaging Agent

• ClinicalTrials.gov Identifier: NCT04029181
• Recruitment Status: Active, not recruiting
• First Posted: July 23, 2019
• Last Update Posted: May 24, 2023
• Sponsor: University Medical Center Groningen
• Information provided by (Responsible Party): Prof.dr. E.G.E. de Vries, University Medical Center Groningen

Tracking Information

• First Submitted Date: June 17, 2019
• First Posted Date: July 23, 2019
• Last Update Posted Date: May 24, 2023
• Actual Study Start Date: February 14, 2019
• Estimated Primary Completion Date: December 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 22, 2019)

• Incidence of adverse events related to tracer administration as assessed by CTCAE v4.0 [ Time Frame: 2 years ]
  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.
• Appropriate dosing of anti-CD8 imaging agent and PET imaging time points [ Time Frame: 2 years ]
  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
• Pharmacokinetics (PK) of anti-CD8 imaging agent [ Time Frame: 2 years ]
  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.
• Immunogenic potential of the anti-CD8 imaging agent by measuring incidence of anti-drug antibodies [ Time Frame: 2 years ]
  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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: July 22, 2019)

• Heterogeneity of tumor uptake of the anti-CD8 imaging agent [ Time Frame: 2 years ]
  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
• Correlation of normal organ uptake of the anti-CD8 imaging agent to (serious) adverse events (possibly) related to immune checkpoint inhibitor treatment [ Time Frame: 2 years ]
  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.
• Correlation of tumor uptake of the anti-CD8 imaging agent and immune cell CD8 expression [ Time Frame: 2 years ]
  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.
• Correlation of anti-CD8 imaging agent normal tissue kinetics with blood kinetics [ Time Frame: 2 years ]
  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.
• Dosimetry [ Time Frame: 2 years ]
  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.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Diagnostic

Condition

• Metastatic Cancer
• Unresectable Malignant Neoplasm

Intervention

Other: Anti-CD8 PET imaging agent

An imaging agent radiolabelled with 89Zr developed for in human PET imaging of CD8

Study Arms

• 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.
  Intervention: Other: Anti-CD8 PET imaging agent
• 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.
  Intervention: Other: Anti-CD8 PET imaging agent

• 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;:

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: May 23, 2023): 47
• Original Estimated Enrollment (submitted: July 22, 2019): 40
• Estimated Study Completion Date: December 2023
• Estimated Primary Completion Date: December 2023 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Netherlands

Administrative Information

• NCT Number: NCT04029181
• Other Study ID Numbers: 201700848
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Prof.dr. E.G.E. de Vries, University Medical Center Groningen
• Original Responsible Party: Same as current
• Current Study Sponsor: University Medical Center Groningen
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

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

• PRS Account: University Medical Center Groningen
• Verification Date: May 2023