A Study of ImmunoPet Imaging Using 89Zr-DFO-REGN5054 in Adult Participants With Solid Cancers Treated With Cemiplimab
Study Details
Study Description
Brief Summary
The primary objective of the study is to determine the safety and tolerability of 89Zr-DFO-REGN5054 alone and in combination with cemiplimab.
The secondary objectives include:
For Part A:
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To characterize the radioactivity pharmacokinetic (PK) profile of 89Zr-DFO-REGN5054
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To establish an adequate mass dose and activity dose of 89Zr-DFO-REGN5054 and optimal post-infusion time for imaging
For Parts A and B:
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To evaluate the association of CD8 expression in tissue biopsies [via immunohistochemistry (IHC)] with tumor 89Zr˗DFO˗REGN5054 uptake in vivo [via positron emission tomography (PET)] and ex vivo (via autoradiography)
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To evaluate the uptake of 89Zr˗DFO˗REGN5054 in tumors, normal CD8-expressing tissues, and blood
Condition or Disease | Intervention/Treatment | Phase |
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Phase 1 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: Single ascending dose of 89Zr˗DFO˗REGN5054 followed by fixed dose of cemiplimab Part A: Doses of 89Zr˗DFO˗REGN5054 may be reduced based upon assessment. |
Drug: 89Zr˗DFO˗REGN5054
Administered by intravenous (IV) infusion during Part A and B.
Drug: cemiplimab
Administered by IV infusion every 3 weeks (Q3W).
Other Names:
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Experimental: Defined dose of 89Zr˗DFO˗REGN5054 followed by fixed dose of cemiplimab Part B: Defined dose of 89Zr˗DFO˗REGN5054 determined in Part A. |
Drug: 89Zr˗DFO˗REGN5054
Administered by intravenous (IV) infusion during Part A and B.
Drug: cemiplimab
Administered by IV infusion every 3 weeks (Q3W).
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Incidence and severity of treatment-emergent adverse events (TEAEs) [Up to day 8, after the infusion of 89Zr˗DFO˗REGN5054]
Part A
- Incidence and severity of TEAEs [Up to approximately week 115]
Part A and B
Secondary Outcome Measures
- Clinical dosimetry based on tissue radiation absorbed dose calculated from positron emission tomography (PET) image acquisition data [On days 1, 5 and 8]
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.
- Clinical dosimetry based on tissue radiation effective dose calculated from PET image acquisition data [On days 1, 5 and 8]
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.
- Concentration of 89Zr-DFO-REGN5054 in serum [On days 1, 5 and 8]
Part A
- Plasma imaging agent activity concentration of area under the curve (AUC0-7) [Up to day 8]
Part A
- 89Zr-DFO-REGN5054 uptake across cluster of differentiation 8 (CD8)-expressing normal tissues and tumors [At the time of imaging, up to day 8]
Part A and Part B
- Blood pool uptake of 89Zr-DFO-REGN5054 with subsequent calculation of standardized uptake value (SUV) tumor-to-blood ratios [At the time of imaging, up to day 8]
Part A and Part B
- Association of 89Zr˗DFO˗REGN5054 autoradiographic signal intensity distribution with CD8 expression in tumor tissues [At Baseline]
Part A and Part B
- Association of 89Zr-DFO-REGN5054 uptake with CD8 expression in tumor tissues [At Baseline]
Part B
- Association of tumor-to-blood ratio of 89Zr-DFO-REGN5054 with CD8 expression in tumor tissues [At Baseline]
Part B
Eligibility Criteria
Criteria
Key Inclusion Criteria:
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Advanced or metastatic solid tumors that may respond to anti-programmed cell death protein 1 (PD-1) immunotherapy
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Measurable disease according to Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 criteria
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Eastern Cooperative Oncology Group (ECOG) performance status of ≤1
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Adequate organ and bone marrow function as defined in the protocol
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Willing and able to comply with clinic visits and study-related procedures (including required tumor biopsy for Part B)
Key Exclusion Criteria:
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Currently receiving another cancer treatment or inadequate time since last therapy, as defined in the protocol
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Has not yet recovered from acute toxicities from prior therapy; exceptions defined in the protocol
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Prior treatment with a blocker of the PD-1/Programmed death ligand 1 (PD-L1) pathway
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Currently receiving or has received chimeric antigen receptor (CAR-T) cell therapy
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Symptomatic or untreated brain metastases, leptomeningeal disease, or spinal cord compression
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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.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Regeneron Pharmaceuticals
Investigators
- Study Director: Clinical Trials Management, Regeneron Pharmaceuticals
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- R5054-ONC-1843
- 2019-001604-38