ImmunoPET With an Anti-CD8 Imaging Agent

NCT04029181 | Active Not Recruiting Phase 1 DMC

• 1 other identifier: 201700848
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 1

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.

Conditions

Metastatic Cancer; Unresectable Malignant Neoplasm

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (5)

• Heterogeneity of tumor uptake of the anti-CD8 imaging agent

  2 years

• Correlation of normal organ uptake of the anti-CD8 imaging agent to (serious) adverse events (possibly) related to immune checkpoint inhibitor treatment

  2 years

• Correlation of tumor uptake of the anti-CD8 imaging agent and immune cell CD8 expression

  2 years

• Correlation of anti-CD8 imaging agent normal tissue kinetics with blood kinetics

  2 years

• Dosimetry

  2 years

Study Arms (2)

Dose finding cohort

EXPERIMENTAL

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

Feasibility cohort

EXPERIMENTAL

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

Interventions

Anti-CD8 PET imaging agent OTHER

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

Dose finding cohort; Feasibility cohort

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Tumor lesion(s) of which a histological biopsy can safely be obtained according to standard clinical care procedures.
• Measurable disease, as defined by standard RECIST v1.1. Previously irradiated lesions should not be counted as target lesions.
• Signed informed consent.
• Age ≥18 at the time of signing informed consent.
• Life expectancy ≥12 weeks.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Ability to comply with the protocol.
• 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).

You may not qualify if:

• Signs or symptoms of infection within 2 weeks prior to anti-CD8 imaging agent injection.
• Prior immune checkpoint inhibitor treatment, including but not limited to anti-PD1 and anti-PD-L1 therapeutic antibodies.
• History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
• 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.
• Pregnant or lactating women.

Sponsors & Collaborators

• University Medical Center Groningen: lead

Study Sites (1)

University Medical Center Groningen

Groningen, Netherlands

Location

Related Publications (2)

• Kist de Ruijter L, van de Donk PP, Hooiveld-Noeken JS, Giesen D, Elias SG, Lub-de Hooge MN, Oosting SF, Jalving M, Timens W, Brouwers AH, Kwee TC, Gietema JA, Fehrmann RSN, Fine BM, Sanabria Bohorquez SM, Yadav M, Koeppen H, Jing J, Guelman S, Lin MT, Mamounas MJ, Eastham JR, Kimes PK, Williams SP, Ungewickell A, de Groot DJA, de Vries EGE. Whole-body CD8+ T cell visualization before and during cancer immunotherapy: a phase 1/2 trial. Nat Med. 2022 Dec;28(12):2601-2610. doi: 10.1038/s41591-022-02084-8. Epub 2022 Dec 5.

  PMID: 36471036 DERIVED

• 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.

  PMID: 36271158 DERIVED

MeSH Terms

Conditions

Neoplasm Metastasis

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• E. G.E. de Vries, MD, PhD

  University Medical Center Groningen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 17, 2019
• First Posted: July 23, 2019
• Study Start: February 14, 2019
• Primary Completion: December 28, 2022
• Study Completion: December 1, 2024
• Last Updated: May 3, 2024

Record last verified: 2024-02

Locations

NL (1)