⁸⁹Zr-Df-IAB22M2C (CD8 PET Tracer) for PET/CT in Patients With Metastatic Solid Tumors

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety of repeat doses ⁸⁹Zr-Df-IAB22M2C and to establish the relationship between ⁸⁹Zr-Df-IAB22M2C PET/CT lesion uptake with CD8+ cells by immunohistochemical staining in patients with selected advanced and metastatic solid malignancies who are scheduled to receive standard of care immunotherapy. The study will also evaluate uptake of ⁸⁹Zr-Df-IAB22M2C by PET/CT in patients at baseline and on immunotherapy.

Detailed Description
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After being informed about the study and potential risks, all patients giving written informed consent will be evaluated to determine eligibility for study entry. Up to 1 week prior to initiation of immunotherapy, patients will receive an injection of ⁸⁹Zr-Df-IAB22M2C (1.0 mCi) and will undergo PET/CT scanning to determine baseline uptake of ⁸⁹Zr-Df-IAB22M2C in tumor lesions and reference tissues. Patients will receive an additional injection of ⁸⁹Zr-Df-IAB22M2C (1.0 mCi) and PET/CT scan 4-6 weeks after starting immunotherapy (on-therapy) to evaluate uptake of ⁸⁹Zr-Df-IAB22M2C in tumor lesions and reference tissues, and to assess potential changes in uptake of ⁸⁹Zr-Df-IAB22M2C compared to the baseline scan.

Official Title
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A Phase II, Open Label, Multi-Dose Study of ⁸⁹Zr-Df-IAB22M2C (CD8 PET Tracer) for Positron Emission Tomography (PET/CT) in Patients With Selected Advanced or Metastatic Solid Malignancies Who Are Scheduled to Receive Standard-of-Care Immunotherapy Only, As Single Agent or in Combination

Conditions
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Positron-Emission Tomography, Metastatic Solid Tumors

Intervention / Treatment
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* Drug: ⁸⁹Zr-Df-IAB22M2C


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants will be eligible for enrollment in the study only if they meet ALL of the following criteria: 1. Patients with advanced or metastatic Melanoma, Non-Small Cell Lung Cancer, Renal Cell Carcinoma or Squamous Cell Carcinoma of the Head and Neck with at least one non-radiated lesion, who are scheduled to begin standard of care immunotherapy. • At least 1 non radiated measurable lesion documented on CT/, MRI (per RECIST criteria 1.1) or are FDG avid on FDG-PET within 45 days prior to first 89Zr-Df-IAB22M2C (CD8 PET Tracer) infusion. At least 1 non-cutaneous lesion that is accessible, per investigator's assessment, and eligible for biopsy. If only a single RECIST measurable lesion is present, investigator to determine if the tumor biopsy could interfere with RECIST assessments of response. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2. Meeting all clinical safety lab values per institution's standard of care, or Investigator's discretion, for patients receiving cancer treatment. Age ≥ 18 years. Ability to understand the purposes and risks of the trial and has signed an IRB-approved informed consent form. Willingness and ability to comply with all protocol required procedures. For men and women of child-producing potential, use of effective double barrier contraceptive methods during the study, up to 30 days after the last administration of the investigational product. Exclusion Criteria: Subjects will NOT be eligible for enrollment in the study if they meet ANY of the following criteria: Serious nonmalignant disease or conditions that in the opinion of the investigator and/or ImaginAb could compromise protocol objectives. Patients with a single RECIST measurable lesion, biopsy of which, per investigator's assessment, is likely to interfere with RECIST assessments of response. Patients who have any splenic disorders, or had splenectomy, that in the opinion of the investigator and/or ImaginAb could compromise protocol objectives. Pregnant women or nursing mothers. 5. Life expectancy < 6 months

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: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ⁸⁹Zr-Df-IAB22M2C Infusion<br>A dose of 3 mCi (±20%) of ⁸⁹Zr-Df-IAB22M2C between 0.5 mg to 1.5 mg of API will be administered intravenously over 5-10 minutes, within one week prior to the onset of immunotherapy, and 5 to 6 weeks after start of IOT. | Drug: ⁸⁹Zr-Df-IAB22M2C<br>* ⁸⁹Zr-Df-IAB22M2C CD8 T cell tracer for Positron Emission Tomography (PET)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation of ⁸⁹Zr-Df-IAB22M2C uptake in biopsied tumors with CD8+ cell measurement by immunohistochemistry (IHC) | Analyze ⁸⁹Zr-Df-IAB22M2C uptake in biopsied tumors as determined by SUV-based quantitative measures (SUVmax, SUVpeak, SUVmean, CD8 tumor volume, and tumor:reference tissue ratio) with CD8+ cell measurement determined by IHC from biopsy samples. | Baseline to 4-5 weeks after the start of immunotherapy | 
| Adverse events | The incident and severity of adverse events per CTCAE criteria will be recorded following repeat doses of ⁸⁹Zr-Df-IAB22M2C. ria, changes in laboratory test results, vital signs, and 12- lead electrocardiogram findings prior to and within 1 hour post injection. | Time of infusion of ⁸⁹Zr-Df-IAB22M2C (Visit 2 Day 1) through 4-5 weeks after the second infusion of ⁸⁹Zr-Df-IAB22M2C | 
| Signs and symptoms of infusion reactions | Signs and symptoms of infusion reactions following repeat doses of ⁸⁹Zr-Df-IAB22M2C will be assessed evaluating the incidence and severity of local and systemic signs and symptoms of infusion reactions | Time of infusion of ⁸⁹Zr-Df-IAB22M2C (Visit 2 Day 1) through 4-5 weeks after the second infusion of ⁸⁹Zr-Df-IAB22M2C | 
| Change in WBC differential including percentages of total WBC and absolute counts: (neutrophils, immature neutrophils, lymphocytes, monocytes, eosinophils, basophils) laboratory values compared to baseline | WBC differential including percentages of total WBC and absolute counts: (neutrophils, immature neutrophils, lymphocytes, monocytes, eosinophils, basophils) laboratory values compared with baseline results. | prior to infusion ⁸⁹Zr-Df-IAB22M2C on study Day 1 and at 4-7 weeks; and 24 +/- 3 hrs after infusions (study Day 2 and 4-7 weeks); and at 4-6 weeks after 2nd infusion | 
| Changes in mean corpscular volume (fL) laboratory values compared to baseline | mean corpscular volume (fL) laboratory values compared with baseline results. | prior to infusion ⁸⁹Zr-Df-IAB22M2C on study Day 1 and at 4-7 weeks; and 24 +/- 3 hrs after infusions (study Day 2 and 4-7 weeks); and at 4-6 weeks after 2nd infusion | 
| Changes in hematocrit (%) laboratory values compared with baseline | hematocrit (%) laboratory values compared with baseline results. | prior to infusion ⁸⁹Zr-Df-IAB22M2C on study Day 1 and at 4-7 weeks; and 24 +/- 3 hrs after infusions (study Day 2 and 4-7 weeks); and at 4-6 weeks after 2nd infusion | 
| Changes in hemoglobin (g/dL) laboratory values compared with baseline | hemoglobin (g/dL) laboratory values compared with baseline results. | prior to infusion ⁸⁹Zr-Df-IAB22M2C on study Day 1 and at 4-7 weeks; and 24 +/- 3 hrs after infusions (study Day 2 and 4-7 weeks); and at 4-6 weeks after 2nd infusion | 
| Changes in platelet count (thousands/ul) laboratory values compared with baseline | platelet count (thousands/ul) laboratory values compared with baseline results. | prior to infusion ⁸⁹Zr-Df-IAB22M2C on study Day 1 and at 4-7 weeks; and 24 +/- 3 hrs after infusions (study Day 2 and 4-7 weeks); and at 4-6 weeks after 2nd infusion | 
| Changes in WBC count (thousands/ul) laboratory values compared with baseline | WBC count (thousands/ul) laboratory values compared with baseline results. | prior to infusion ⁸⁹Zr-Df-IAB22M2C on study Day 1 and at 4-7 weeks; and 24 +/- 3 hrs after infusions (study Day 2 and 4-7 weeks); and at 4-6 weeks after 2nd infusion | 
| Changes in RBC count (millions/uL) laboratory values compared with baseline | RBC count (millions/uL) laboratory values compared with baseline results. | prior to infusion ⁸⁹Zr-Df-IAB22M2C on study Day 1 and at 4-7 weeks; and 24 +/- 3 hrs after infusions (study Day 2 and 4-7 weeks); and at 4-6 weeks after 2nd infusion | 
| Changes in blood glucose (mg/dL) laboratory values compared with baseline | blood glucose (mg/dL) laboratory values compared with baseline results. | prior to infusion ⁸⁹Zr-Df-IAB22M2C on study Day 1 and at 4-7 weeks; and 24 +/- 3 hrs after infusions (study Day 2 and 4-7 weeks); and at 4-6 weeks after 2nd infusion | 
| Changes in chloride (mmol/L) laboratory values compared with baseline | chloride (mmol/L) laboratory values compared with baseline results. | prior to infusion ⁸⁹Zr-Df-IAB22M2C on study Day 1 and at 4-7 weeks; and 24 +/- 3 hrs after infusions (study Day 2 and 4-7 weeks); and at 4-6 weeks after 2nd infusion | 
| Changes in potassium (mmol/L) laboratory values compared with baseline | Potassium (mmol/L) laboratory values compared with baseline results. | prior to infusion ⁸⁹Zr-Df-IAB22M2C on study Day 1 and at 4-7 weeks; and 24 +/- 3 hrs after infusions (study Day 2 and 4-7 weeks); and at 4-6 weeks after 2nd infusion | 
| Changes in sodium (mmol/L) laboratory values compared with baseline | sodium (mmol/L) laboratory values compared with baseline results. | prior to infusion ⁸⁹Zr-Df-IAB22M2C on study Day 1 and at 4-7 weeks; and 24 +/- 3 hrs after infusions (study Day 2 and 4-7 weeks); and at 4-6 weeks after 2nd infusion | 
| Changes in uric acid (mg/dL) laboratory values compared with baseline | uric acid (mg/dL) laboratory values compared with baseline results. | prior to infusion ⁸⁹Zr-Df-IAB22M2C on study Day 1 and at 4-7 weeks; and 24 +/- 3 hrs after infusions (study Day 2 and 4-7 weeks); and at 4-6 weeks after 2nd infusion | 
| Changes in serum creatinine (mg/dL) laboratory values compared with baseline | serum creatinine (mg/dL) laboratory values compared with baseline results. | prior to infusion ⁸⁹Zr-Df-IAB22M2C on study Day 1 and at 4-7 weeks; and 24 +/- 3 hrs after infusions (study Day 2 and 4-7 weeks); and at 4-6 weeks after 2nd infusion | 
| Changes in GGT (U/L) laboratory values compared with baseline | GGT (U/L) laboratory values compared with baseline results. | prior to infusion ⁸⁹Zr-Df-IAB22M2C on study Day 1 and at 4-7 weeks; and 24 +/- 3 hrs after infusions (study Day 2 and 4-7 weeks); and at 4-6 weeks after 2nd infusion | 
| Changes in BUN (mg/dL) laboratory values compared with baseline | BUN (mg/dL) laboratory values compared with baseline results. | prior to infusion ⁸⁹Zr-Df-IAB22M2C on study Day 1 and at 4-7 weeks; and 24 +/- 3 hrs after infusions (study Day 2 and 4-7 weeks); and at 4-6 weeks after 2nd infusion | 
| Changes in LDH (U/L) laboratory values comapared with baseline | LDH (U/L) laboratory values compared with baseline results. | prior to infusion ⁸⁹Zr-Df-IAB22M2C on study Day 1 and at 4-7 weeks; and 24 +/- 3 hrs after infusions (study Day 2 and 4-7 weeks); and at 4-6 weeks after 2nd infusion | 
| Bilirubin, direct and total (mg/dL) laboratory values | Change/shifts in Bilirubin, direct and total (mg/dL) laboratory values compared with baseline results. | prior to infusion ⁸⁹Zr-Df-IAB22M2C on study Day 1 and at 4-7 weeks; and 24 +/- 3 hrs after infusions (study Day 2 and 4-7 weeks); and at 4-6 weeks after 2nd infusion | 
| ALP laboratory values | Change/shifts in ALP (U/L) laboratory values compared with baseline results. | prior to infusion ⁸⁹Zr-Df-IAB22M2C on study Day 1 and at 4-7 weeks; and 24 +/- 3 hrs after infusions (study Day 2 and 4-7 weeks); and at 4-6 weeks after 2nd infusion | 
| ALT laboratory values | Change/shifts in ALT (U/L) laboratory values compared with baseline results. | prior to infusion ⁸⁹Zr-Df-IAB22M2C on study Day 1 and at 4-7 weeks; and 24 +/- 3 hrs after infusions (study Day 2 and 4-7 weeks); and at 4-6 weeks after 2nd infusion | 
| AST laboratory values | Change/shifts in AST (U/L) laboratory values compared with baseline results. | prior to infusion ⁸⁹Zr-Df-IAB22M2C on study Day 1 and at 4-7 weeks; and 24 +/- 3 hrs after infusions (study Day 2 and 4-7 weeks); and at 4-6 weeks after 2nd infusion | 
| 12-Lead electrocardiogram | Proportion of subjects with abnormal electrocardiogram findings prior to and within 1 hour post injection. | Within 60 minutes post-infusion (study visits 2 and 5) | 
| Evaluation of blood pressure | Changes/shifts in blood pressure (systolic and diastolic) | 15 +/- 5 minutes prior to infusion and within 60 minutes post-infusion (study visits 2 and 5) and 4-6 weeks after 2nd infusion (study visit 8) | 
| Evaluation of heart rate | Changes/shifts in heart rate | 15 +/- 5 minutes prior to infusion and within 60 minutes post-infusion (study visits 2 and 5) and 4-6 weeks after 2nd infusion (study visit 8) | 
| Evaluation of respiration rate | Changes/shifts in respiration rate | 15 +/- 5 minutes prior to infusion and within 60 minutes post-infusion (study visits 2 and 5) and 4-6 weeks after 2nd infusion (study visit 8) | 
| Evaluation of temperature | Changes/shifts in temperature | 15 +/- 5 minutes prior to infusion and within 60 minutes post-infusion (study visits 2 and 5) and 4-6 weeks after 2nd infusion (study visit 8) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of Baseline and On-treatment ⁸⁹Zr-Df-IAB22M2C uptake and distribution in tumors and lymphoid organs, and measurement of change between the paired observations | Assessment of Baseline and On-treatment ⁸⁹Zr-Df-IAB22M2C uptake and distribution in tumors and lymphoid organs, and measurement of change between the paired observations as determined by: Tumor uptake analysis as described by visual scoring scales Lymph node chain visibility defined as location and number of nodes in lymph node chains identified with elevated ⁸⁹Zr-Df-IAB22M2C activity. SUV-based quantitative analysis (e.g. SUVmax, SUVpeak, SUVmean, CD8 tumor volume (volume of tumor tissues with increased CD8 uptake with SUV >40% SUVmax), and Tumor:Reference ratios Visual and SUV-based quantitative analysis (e.g. SUVmax, SUVpeak, SUVmean) in tumor and reference tissue including lymph nodes, spleen, and bone marrow. | 5 weeks | 
| Measurement of change in ⁸⁹Zr-Df-IAB22M2C (CD8 PET Tracer) uptake in biopsied tumors as determined by SUV-based quantitative analysis | Measurement of change in ⁸⁹Zr-Df-IAB22M2C (CD8 PET Tracer) uptake in biopsied tumors as determined by SUV-based quantitative analysis (e.g. SUVmax, SUVpeak, SUVmean, CD8 tumor volume (volume of tumor tissues with increase CD8 uptake with SUV > 40% SUVmax) and Tumor: Reference ratio from Baseline to On- Treatment PET scans and correlation with change in CD8+ T cells as determined by IHC from biopsy samples obtained prior to and 4 to 7 weeks after the start of immunotherapy. | 7 weeks | 
| Description of biodistribution patterns of ⁸⁹Zr-Df-IAB22M2C (CD8 PET Tracer) on PETbaseline and PETTx and any changes in biodistribution between baseline and On-Treatment. | Description of biodistribution patterns of ⁸⁹Zr-Df-IAB22M2C (CD8 PET Tracer) on PETbaseline and PETTx and any changes in biodistribution between baseline and On-Treatment. PETbaseline and PETTx scans compared to change in CD8+ T cells in tumor lesions by IHC if the same lesion was biopsied at Baseline and On-Treatment visits | 7 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PET/CT, ⁸⁹Zr-Df-IAB22M2C, CD8, Imaging