Study of ImmunoPet Imaging of PD-L1 in Tumors Using 89Zr-DFO-REGN3504 in Adult Participants With Advanced PD-L1 Positive Malignancies

• ClinicalTrials.gov Identifier: NCT03746704
• Recruitment Status: Terminated
• First Posted: November 20, 2018
• Last Update Posted: February 23, 2022
• Sponsor: Regeneron Pharmaceuticals
• Information provided by (Responsible Party): Regeneron Pharmaceuticals

Tracking Information

• First Submitted Date: November 15, 2018
• First Posted Date: November 20, 2018
• Last Update Posted Date: February 23, 2022
• Actual Study Start Date: September 4, 2019
• Actual Primary Completion Date: July 8, 2021 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: November 21, 2019): Incidence and severity of treatment-emergent adverse events (TEAEs) [ Time Frame: Baseline through 90 days after last dose of tracer infusion ]
• Original Primary Outcome Measures (submitted: November 15, 2018): Incidence and severity of treatment-emergent adverse events (TEAEs) [ Time Frame: Baseline through 21 days ]

Current Secondary Outcome Measures (submitted: November 15, 2018)

• Standardized uptake value (SUV) of 89Zr˗DFO˗REGN3504 in the blood pool [ Time Frame: Up to day 8 ]
  Part A
• Clinical dosimetry based on the equivalent dose of radiation [ Time Frame: Up to day 8 ]
  Part A
• Clinical dosimetry based on the effective dose of radiation [ Time Frame: Up to day 8 ]
  Part A
• SUVs across the tumor region of interest (ROIs) [ Time Frame: Up to day 8 ]
  Part A
• Maximal SUVs (SUVmax) within tumor ROIs [ Time Frame: Up to day 8 ]
  Part A
• Pharmacokinetics (PK) of 89Zr˗DFO˗REGN3504; plasma tracer activity concentration of area under the curve (AUC0-7) [ Time Frame: Up to day 8 ]
  Part A
• Change in SUV of 89Zr˗DFO˗REGN3504 in the blood pool [ Time Frame: Up to day 36 ± 14 days ]
  Part B
• Change in SUVs across the tumor ROIs [ Time Frame: Up to day 36 ± 14 days ]
  Part B
• Change in SUVmax within the tumor ROIs [ Time Frame: Up to day 36 ± 14 days ]
  Part B
• Biodistribution of 89Zr˗DFO˗REGN3504 [ Time Frame: Up to day 36 ± 14 days ]
  Part B

• 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: Study of ImmunoPet Imaging of PD-L1 in Tumors Using 89Zr-DFO-REGN3504 in Adult Participants With Advanced PD-L1 Positive Malignancies
• Official Title: A Phase 1, First-in-Human Study of ImmunoPET Imaging of PD-L1 in Tumors Using 89Zr-DFO-REGN3504, an Anti-PD-L1 Tracer for Positron Emission Tomography in Patients With Advanced PD-L1 Positive Malignancies

Brief Summary

The primary objective of the study is to determine the safety and tolerability of 89Zr-DFO-REGN3504.

The secondary objectives of the study are:

Study Part A only:

• To establish adequate mass dose and activity dose of 89Zr˗DFO˗REGN3504 and optimal post-infusion imaging time, as assessed by imaging and blood draw after tracer infusion

Study Part B only:

• To establish test/re-test reliability of positron emission tomography (PET) measures as assessed on 2 separate tracer infusions at adequate mass dose and optimal imaging time point as determined in Part A
• To characterize the pharmacokinetic (PK) profile of 89Zr˗DFO˗REGN3504 based on tracer plasma activity concentration

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Basic Science
• Condition: Advanced PD-L1 Positive Malignancies

Intervention

Drug: 89Zr˗DFO˗REGN3504

89Zr˗DFO˗REGN3504

Study Arms

Experimental: 89Zr˗DFO˗REGN3504

Part A: Cohorts 1-3 Part B

Intervention: Drug: 89Zr˗DFO˗REGN3504

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: February 7, 2022): 2
• Original Estimated Enrollment (submitted: November 15, 2018): 28
• Actual Study Completion Date: July 8, 2021
• Actual Primary Completion Date: July 8, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Key Inclusion Criteria:

• Participants with at least 1 radiologically measurable (by RECIST 1.1) lesion (Note: Lesions 10 mm in diameter or larger at the high end Program Dealth-Ligand 1 (PD-L1) expression are expected to be detectable by 89Zr-DFO-REGN3504 PET imaging).
• Availability of an archival, formalin-fixed, paraffin-embedded (FFPE) tumor tissue sample (blocks or slides) from a primary/metastatic/recurrent site, which has not been previously irradiated, with presence of any PD-L1 expression by Immunohistochemistry (IHC) in tumor or immune cells, performed by a Clinical Laboratory Improvement Amendments of 1988 (CLIA), a certified laboratory, using either freshly cut or archived FFPE slides. If the analysis will be done using archived FFPE slides, the slides must be <6 months old after being cut from the tissue block. The age of a tissue block is not limited. If the patient has a report of ≥1% PD-L1 expression, there is no need to repeat the assay; the report has no time limit.
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤2 (Oken, 1982) and anticipated life expectancy of at least 3 months
• Adequate organ and bone marrow function

Key Exclusion Criteria:

• Participants receiving therapy with a monoclonal antibody against PD-L1 (eg. durvalumab, atezolizumab, avelumab) or have received treatment with anti-PD-L1 within 135 days prior to the 89Zr˗DFO˗REGN3504 infusion date
• For Part B only, participants in whom anti-PD-1 therapy was initiated 1 month or less, prior to the 89Zr˗DFO˗REGN3504 infusion date
• Active or untreated brain metastases or spinal cord compression. Participants are eligible if the central nervous system (CNS) metastases are adequately treated and participants' neurological symptoms have returned to baseline levels (except for residual signs or symptoms related to the CNS treatment) for at least 2 weeks prior to enrollment. Participants with brain metastases must be off doses of corticosteroid therapy that are considered by the investigator to be immunosuppressive
• Known history of human immunodeficiency virus or known acquired immunodeficiency syndrome indicating uncontrolled active infection. Participants on highly active antiretroviral therapy with undetectable RNA levels and CD4 counts above 350 are permitted
• Receipt of an investigational compound or device within 30 days of screening or within 5 half-lives of the investigational compound or therapy being studied (whichever is greater)
• Major surgery or significant traumatic injury within 4 weeks prior to first dose of 89Zr˗DFO˗REGN3504
• Known psychiatric or substance abuse disorder, including current use of any illicit drugs, that would interfere with the participant's participation in, or compliance with the requirements of, the study
• History of hypersensitivity response to any protein therapeutics (eg, recombinant proteins, vaccines, IV immune globulins, monoclonal antibodies, receptor traps). If a patient intends to receive a COVID-19 vaccine during Part A only, participation in the dose-escalation part of the study should be delayed at least 1 week after the final dose of COVID-19 vaccine before the start of study drug.
• Sexually active men and women of childbearing potential who are unwilling to practice highly effective contraception prior to the initial dose/start of the first treatment, during the study, and for at least 6 months after the last dose.
• Part B only: Has been enrolled in Part A

Note: Other Protocol Inclusion/Exclusion Criteria apply

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: United States

Administrative Information

• NCT Number: NCT03746704
• Other Study ID Numbers: R3504-ONC-1701
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

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

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: All individual patient data (IPD) that underlie publicly available results will be considered for sharing
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Informed Consent Form (ICF)
• Supporting Materials: Clinical Study Report (CSR)
• Supporting Materials: Analytic Code
• Time Frame: Individual anonymized participant data will be considered for sharing once the indication has been approved by a regulatory body, if there is legal authority to share the data and there is not a reasonable likelihood of participant re-identification.
• Access Criteria: Qualified researchers may request access to anonymized patient level data or aggregate study data when Regeneron has received marketing authorization from major health authorities (e.g., FDA, European Medicines Agency (EMA), Pharmaceuticals and Medical Devices Agency (PMDA), etc) for the product and indication, has the legal authority to share the data, and has made the study results publicly available (eg, scientific publication, scientific conference, clinical trial registry).
• URL: https://vivli.org/

• Current Responsible Party: Regeneron Pharmaceuticals
• Original Responsible Party: Same as current
• Current Study Sponsor: Regeneron Pharmaceuticals
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Clinical Trial Management; Regeneron Pharmaceuticals

• PRS Account: Regeneron Pharmaceuticals
• Verification Date: February 2022