LAG3 PET Imaging in Advanced Solid Tumors

NCT04706715 | Active Not Recruiting Phase 1 DMC

• 1 other identifier: 202000570
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 1

Brief Summary

This is an investigator-initiated, single-center, open-label clinical trial designed to evaluate the safety and PK of the PET tracer 89Zr-DFO-REGN3767 in patients prior to and during treatment.

Conditions

Metastatic Solid Tumor

Keywords

cancer; immune checkpoint inhibitor; positron emission tomography; LAG-3

Outcome Measures

Primary Outcomes (3)

• Optimal 89Zr-DFO-REGN3767 dose and PET imaging timepoint

  Determine the optimal 89Zr-DFO-REGN3767 dose and optimal PET imaging timepoint.

  2 years

• Pharmacokinetics (PK) of 89Zr-DFO-REGN3767

  Description of PK of 89Zr-DFO-REGN3767 by measuring standardized uptake value (SUV) on PET scans performed 0, 2, 4 and/or 7 days after tracer injection.

  2 years

• Incidence of adverse events related to 89Zr-DFO-REGN3767 administration as assessed by CTCAE v5.0

  Safety assessment through summaries of adverse events, changes in laboratory test results (if evaluation is indicated) and changes in vital signs. Adverse event data will be recorded and summarized according to NCI CTCAE v5.0

  2 years

Secondary Outcomes (4)

• Heterogeneity of 89Zr-DFO-REGN3767 antibody tumor uptake

  2 years

• Correlation of tumor tracer uptake with tumor and immune cell LAG3 expression

  2 years

• Correlation of tumor tracer uptake with response to cemiplimab

  2 years

• Assessment of changes in tumor and normal organ uptake

  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. After completion of imaging, patients will start treatment with cemiplimab with or without platinum-based chemotherapy.

Other: 89Zr-DFO-REGN3767; Drug: Cemiplimab

Feasibility cohort

EXPERIMENTAL

The purpose of part B of the study is to analyze the PK of 89Zr-DFO-REGN3767 in patients before and during treatment with cemiplimab with or without platinum-based chemotherapy.

Other: 89Zr-DFO-REGN3767; Drug: Cemiplimab

Interventions

89Zr-DFO-REGN3767 OTHER

Anti-LAG-3 PET imaging tracer

Dose finding cohort; Feasibility cohort

Cemiplimab DRUG

Cemiplimab 350 mg every 3 weeks with or without platinum-based chemotherapy.

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:

• Age ≥ 18 years at the time of signing informed consent.
• Patients with histologically confirmed diagnosis of locally advanced or metastatic solid cancer types who, according to the opinion of the investigator, based on available clinical data, may benefit from PD1 antibody with or without platinum-based chemotherapy.
• At least 1 lesion that is accessible per investigator's assessment and eligible for biopsy 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 except for lesions that have progressed after radiotherapy.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Life expectancy ≥ 12 weeks.
• Adequate organ and bone marrow function as defined below:
• Hemoglobin ≥9.0 g/dL
• Absolute neutrophil count ≥1.5 x 109/L
• Absolute lymphocyte count ≥0.75 x 109/L
• Platelet count ≥100 x 109/L
• Serum creatinine ≤1.5 x upper limit of normal (ULN) or estimated glomerular filtration rate \> 30 mL/min/1.73 m2. A 24-hour urine creatinine collection may substitute for the calculated creatinine clearance to meet eligibility criteria.
• Adequate hepatic function:
• i. Total bilirubin ≤1.5 x ULN (≤3 x ULN if liver tumor involvement); Patients with Gilbert's syndrome do not need to meet total bilirubin requirements, provided their total bilirubin is unchanged from their baseline. Gilbert's syndrome must be documented appropriately as past medical history.
• ii. Aspartate aminotransferase (AST) ≤2.5 x ULN (≤5 x ULN if liver tumor involvement) iii. Alanine aminotransferase (ALT) ≤2.5 x ULN (≤5 x ULN if liver tumor involvement) iv. Alkaline phosphatase (ALP) ≤2.5 x ULN (≤5 x ULN if liver or bone tumor involvement)

You may not qualify if:

• Treatment with any approved anti-cancer therapy, investigational agent, or participation in another clinical trial with therapeutic intent within 28 days prior to 89Zr-DFO-REGN3767 injection.
• Prior ICI treatment, including but not limited to anti-PD1 and anti-PD-L1 therapeutic antibodies.
• Any unresolved toxicity (\>CTCAE grade 2) from previous anti-cancer therapy. Subjects with irreversible toxicity that is not reasonably expected to be exacerbated by the investigational product may be included (e.g., hearing loss, peripherally neuropathy)
• Symptomatic, untreated brain metastasis, leptomeningeal disease, or spinal cord compression. Patients are eligible if central nervous system (CNS) metastases are adequately treated and neurologically stable for at least 2 weeks prior to enrollment.
• Documented allergic or acute hypersensitivity reaction attributed to antibody treatments.
• Major surgical procedure other than for diagnosis within 28 days prior to 89Zr-DFO-REGN3767 injection or anticipation of need for a major surgical procedure during the course of the study.
• For patients that will be treated with cemiplimab in combination with platinum containing chemotherapy, the following additional criteria apply:
• Age \> 70 years
• Leucopenia \<3 x 109/L
• Estimated glomerular filtration rate \< 60 mL/min/1.73 m2
• Cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), unstable angina, unstable cardiac arrhythmias, myocardial infarction \< 3 months ago, or cerebrovascular accident \< 6 months ago.
• Hearing loss
• History of autoimmune disease, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematous, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis or glomerulonephritis.
• Patients with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone may be eligible for his study.
• Patients with controlled type I diabetes mellitus on a stable dose of insulin regimen may be eligible for this study.

Sponsors & Collaborators

• University Medical Center Groningen: lead
• Regeneron Pharmaceuticals: collaborator

Study Sites (1)

University Medical Center Groninen

Groningen, 9713 GZ, Netherlands

Location

MeSH Terms

Conditions

Neoplasm Metastasis; Neoplasms

Interventions

cemiplimab

Condition Hierarchy (Ancestors)

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

Study Officials

• E GE de Vries, MD, PhD

  University Medical Center Groningen

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: December 3, 2020
• First Posted: January 13, 2021
• Study Start: January 18, 2022
• Primary Completion: November 1, 2025
• Study Completion: November 1, 2025
• Last Updated: May 31, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)