A Study of ImmunoPet Imaging Using 89Zr-DFO-REGN5054 in Adult Participants With Solid Cancers Treated With Cemiplimab

Study Overview
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Brief Summary
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This study is researching an experimental drug called 89Zr-DFO-REGN5054 and cemiplimab. The study is focused on patients with a type of cancer that can be potentially imaged using 89Zr-DFO-REGN5054 and show special tumor features that may be important to the way the immune system fights cancer. The aim of the study is to study the safety and tolerability (how your body reacts to the drug) of the imaging agent 89Zr-DFO-REGN5054. The study is looking at several other research questions, including: What side effects may happen from taking the study drugs How much study drug is in your blood at different times Whether the body makes antibodies against the study drugs (which could make the study drugs less effective or could lead to side effects)

Official Title
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A First-in-Human Study of 89Zr-DFO-REGN5054 (Anti-CD8) Positron Emission Tomography in Patients With Solid Malignancies Treated With Cemiplimab

Conditions
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Advanced Solid Tumor, Metastatic Solid Tumor

Intervention / Treatment
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* Drug: 89Zr˗DFO˗REGN5054
* Drug: cemiplimab


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Advanced or metastatic solid tumors that may respond to anti-programmed cell death 1 (PD-1) immunotherapy Measurable disease according to Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 criteria Eastern Cooperative Oncology Group (ECOG) performance status of ≤1 Adequate organ and bone marrow function as defined in the protocol Willing and able to comply with clinic visits and study-related procedures (including required tumor biopsy for Part B) Key Exclusion Criteria: Currently receiving another cancer treatment or inadequate time since last therapy, as defined in the protocol Has not yet recovered from acute toxicities from prior therapy; exceptions defined in the protocol Prior treatment with a blocker of the PD-1/Programmed death ligand 1 (PD-L1) pathway Currently receiving or has received chimeric antigen receptor (CAR-T) cell therapy Symptomatic or untreated brain metastases, leptomeningeal disease, or spinal cord compression Known history of or any evidence of interstitial lung disease, active, noninfectious pneumonitis (past 5 years) or active tuberculosis NOTE: Other protocol defined 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: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single ascending dose of 89Zr˗DFO˗REGN5054 followed by fixed dose of cemiplimab<br>Part A: Doses of 89Zr˗DFO˗REGN5054 may be reduced based upon assessment. | Drug: 89Zr˗DFO˗REGN5054<br>* Administered by intravenous (IV) infusion during Part A and B.<br>Drug: cemiplimab<br>* Administered by IV infusion every 3 weeks (Q3W).<br>* Other names: Libtayo;|
| Experimental: Defined dose of 89Zr˗DFO˗REGN5054 followed by fixed dose of cemiplimab<br>Part B: Defined dose of 89Zr˗DFO˗REGN5054 determined in Part A. | Drug: 89Zr˗DFO˗REGN5054<br>* Administered by intravenous (IV) infusion during Part A and B.<br>Drug: cemiplimab<br>* Administered by IV infusion every 3 weeks (Q3W).<br>* Other names: Libtayo;|

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) | Part A | Up to day 8, after the infusion of 89Zr˗DFO˗REGN5054 | 
| Incidence and severity of TEAEs | Part A and B | Up to approximately week 115 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical dosimetry based on tissue radiation absorbed dose calculated from positron emission tomography (PET) image acquisition data | After injection of 37 megabecquerel (MBq) of 89Zr-DFO-REGN5054, a series of whole-body positron emission tomography (PET) images will be obtained over a period of up to 8 days and corrected for attenuation by low-dose computed tomography (CT) scans using PET/CT. The radiation effective dose per organ/tissue will be calculated for each organ using Organ Level INternal Dose Assessment/EXponential Modeling (OLINDA/EXM). The unit of effective dose per organ/tissue will be millisievert per Minimum Base Quantity (MBq) for each participant's organ/tissue. The final values for each organ will be averaged across participants for each mass dose | On days 1, 5 and 8 | 
| Clinical dosimetry based on tissue radiation effective dose calculated from PET image acquisition data | After injection of 37 MBq of 89Zr-DFO-REGN5054, a series of whole-body PET images will be obtained over a period of up to 8 days and corrected for attenuation by low-dose CT scans using PET/CT. The radiation effective dose for the whole body will be calculated using OLINDA/EXM software. The unit of effective dose will be millisievert per MBq for the whole body for each participant. The final values will be averaged across participants for each mass dose. | On days 1, 5 and 8 | 
| Concentration of 89Zr-DFO-REGN5054 in serum | Part A | On days 1, 5 and 8 | 
| Serum imaging agent activity concentration of area under the curve (AUC0-7) | Part A | Up to day 8 | 
| 89Zr-DFO-REGN5054 uptake across cluster of differentiation 8 (CD8)-expressing normal tissues and tumors | Part A and Part B | At the time of imaging, up to day 8 | 
| Blood pool uptake of 89Zr-DFO-REGN5054 with subsequent calculation of standardized uptake value (SUV) tumor-to-blood ratios | Part A and Part B | At the time of imaging, up to day 8 | 
| Association of 89Zr˗DFO˗REGN5054 autoradiographic signal intensity distribution with CD8 expression in tumor tissues | Part A and Part B | At Baseline | 
| Association of 89Zr-DFO-REGN5054 uptake with CD8 expression in tumor tissues | Part B | At Baseline | 
| Association of tumor-to-blood ratio of 89Zr-DFO-REGN5054 with CD8 expression in tumor tissues | Part B | At Baseline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Positron Emission Tomography (PET) scan, Immuno-PET