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

Study Overview
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Brief Summary
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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

Official Title
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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

Conditions
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Advanced PD-L1 Positive Malignancies

Intervention / Treatment
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* Drug: 89Zr˗DFO˗REGN3504


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 89Zr˗DFO˗REGN3504<br>Part A: Cohorts 1-3 Part B | Drug: 89Zr˗DFO˗REGN3504<br>* 89Zr˗DFO˗REGN3504<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and severity of treatment-emergent adverse events (TEAEs) |  | Baseline through 90 days after last dose of tracer infusion | 

Secondary Outcome Measures

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