Clinical trial NCT03802123
Conditions: Positron-Emission Tomography Metastatic Solid Tumors
Keywords: PET/CT ⁸⁹Zr-Df-IAB22M2C CD8 Imaging
Sponsor: ImaginAb, Inc.
Start date: 2018-12-18; Completion date: 2022-07-18
Enrollment: 52 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
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:
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.

Arms: arm 1: 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.
Interventions: intervention 1: ⁸⁹Zr-Df-IAB22M2C
Intervention descriptions: intervention 1: ⁸⁹Zr-Df-IAB22M2C CD8 T cell tracer for Positron Emission Tomography (PET)

Protocol documents:
Prot_SAP_000.pdf: 
 
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.  
 
Protocol Number: 
IAB-CD8-201 
Version Number: 
Version 3.1 
Version Date 
28 OCT 2020 
Development Phase: 
Phase II 
Investigational Compound: 
89Zr-Df-IAB22M2C (CD8 PET Tracer) 
NCT Number: 
NCT03802123 
 
 
Sponsor: 
ImaginAb Inc. 
 
 
 
 
 
 


Name of Sponsor/Company: ImaginAb Inc. 
Name of Study Product: 89Zr-Df-IAB22M2C 
Protocol Number:  
IAB-CD8-201 
Indication: Patients with Selected Advanced and 
Metastatic Solid Tumors including Melanoma, Non-
Small Cell Lung Cancer, Renal Cell Carcinoma, 
Squamous Cell Carcinoma of the Head and Neck, 
Colorectal Cancer-MSI high, Triple Negative Breast, 
Bladder, Cervical, and Esophagogastric Cancers 
Title of Study: 
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 As Single Agent or In Combination. 
 
Study Center: Up to 20 research sites in USA, Canada, Europe and Australia 
Planned Number of Subjects:  
Approximately 47 Subjects 
Study Development Phase:  
II 
Objectives:  
Primary Objectives: 
• Evaluate safety of repeat doses of 89Zr-Df-IAB22M2C (CD8 PET Tracer) 
• Establish the relationship between 89Zr-Df-IAB22M2C (CD8 PET Tracer) PET/CT lesion uptake with 
CD8+ cells by Immunohistochemical staining (IHC)   
Secondary Objective: 
• Assess 89Zr-Df-IAB22M2C (CD8 PET Tracer) uptake at Baseline and On-treatment in tumor lesions and 
reference tissues, including CD8+-cell rich reference tissues 
• Measure potential change in 89Zr-Df-IAB22M2C (CD8 PET Tracer) uptake on PET in tumor lesions and 
reference tissues, including CD8+-cell rich tissues reference between baseline and On-treatment. 
•  Measure potential changes in 89Zr-Df-IAB22M2C (CD8 PET Tracer) uptake on PETbaseline and PETTx   scans 
compared to change in CD8+ cells in tumor lesions by IHC if the same lesion was biopsied at Baseline and 
On-Treatment visits 
• Assess biodistribution for 89Zr-Df-IAB22M2C (CD8 PET Tracer) on PETbaseline and PETTx scans. 
Exploratory Objectives: 
• Explore visual and quantitative 89Zr-Df-IAB22M2C (CD8 PET Tracer) PET measurements that best 
correlate with CD8+ cells as determined by IHC. 
• Estimate positive predictive value, negative predictive value, sensitivity and specificity of 89Zr-IAB22M2C 
(CD8 PET Tracer) PET for detecting CD8+ cells as determined by IHC. 
• Explore the visual and quantitative 89Zr-Df-IAB22M2C (CD8 PET Tracer) PET measurements with clinical 
outcomes.  
• Evaluate the visual and quantitative 89Zr-Df-IAB22M2C (CD8 PET Tracer) PET measurements with 
RECIST 1.1 radiology responses  
• Evaluate the correlation of 89Zr-Df-IAB22M2C (CD8 PET Tracer) uptake with immune infiltrates and other 
molecular biomarkers (such as CD4, CD8, PD-1 and PD-L1) expression by IHC 
•  


Study Outcomes: 
Primary Outcome Measure: 
• 
The safety and tolerability of repeat doses of 89Zr-Df-IAB22M2C (CD8 PET Tracer) will be assessed by 
local and systemic signs and symptoms of infusion reactions, incidence of adverse events per CTCAE 
criteria, changes in laboratory test results, vital signs and 12-lead electrocardiogram (ECG) findings prior 
to and within 1 hour post injection. 
• 
Correlation of 89Zr-Df-IAB22M2C (CD8 PET Tracer) uptake in biopsied tumors as determined by SUV-
based quantitative measures :SUVmax, SUVpeak, SUVmean, CD8 tumor volume (volume of tumor 
tissues with increased CD8 uptake with SUV > 40% SUVmax), and Tumor: Reference ratios with CD8+ 
cell measurements as determined by IHC from biopsy samples. 
Secondary Outcome Measures: 
• 
Assessment of Baseline and On-Treatment 89Zr-Df-IAB22M2C (CD8 PET Tracer) uptake and distribution 
in tumors and lymphoid organs, and measurement of change between the paired observations, as 
determined by: 
o 
Tumor uptake analysis as described by visual scoring scales  
o 
Lymph node chain visibility defined as location and number of nodes in lymph node chains 
identified with elevated 89Zr-Df-IAB22M2C (CD8 PET Tracer) activity. 
• 
Assessment of Baseline and On-Treatment 89Zr-Df-IAB22M2C (CD8 PET Tracer) uptake and distribution 
in tumors and lymphoid organs and measurement of change between the paired observations, as 
determined by: 
o 
SUV-based quantitative analysis: SUVmax, SUVpeak, SUVmean, CD8 tumor volume (volume 
of tumor tissues with increased CD8 uptake with SUV > 40% SUVmax), and Tumor: Reference 
ratios 
o 
Visual and SUV-based quantitative analysis ( SUVmax, SUVpeak, SUVmean) in tumor and 
reference tissues including lymph nodes, spleen and bone marrow. 
• 
Measurement of change in 89Zr-Df-IAB22M2C (CD8 PET Tracer) uptake in biopsied tumors as 
determined by SUV-based quantitative analysis : 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+ cells as determined 
by IHC from biopsy samples obtained prior to and 4 to 7 weeks after the start of immunotherapy. 
• 
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. 
Exploratory Outcome Measures: 
• 
Correlation of visual and quantitative 89Zr-Df-IAB22M2C (CD8 PET Tracer) uptake in tumor lesions with 
change in CD8+ cells as determined by IHC from biopsy samples obtained prior to and 4 to 7 weeks after 
the start of immunotherapy. 
• 
Estimation of positive predictive value, negative predictive value, sensitivity and specificity of 89Zr-
IAB22M2C (CD8 PET Tracer) PET for detecting CD8+ cells as determined by IHC. 
• 
Correlation of 89Zr-Df-IAB22M2C (CD8 PET Tracer) uptake with clinical outcomes (response rates, 
duration of response, disease stability rate and PFS) at defined intervals as determined by the local 
investigator. 
• 
Correlation of 89Zr-Df-IAB22M2C (CD8 PET Tracer) uptake with radiologic responses based upon: 
o 
Correlation of subject response by RECIST 1.1 compared to visual and quantitative SUV-based 
analysis  
o 
Correlation of RECIST 1.1 target lesion response as determined by best change in lesion diameter 
while on immunotherapy compared to visual and quantitative SUV-based analysis at baseline 
and On-treatment PET/CT scans. 
• 
Correlation of 89Zr-Df-IAB22M2C (CD8 PET Tracer) tumor and lymph node uptake with immune 
infiltrates and other molecular biomarker (CD8) expression by IHC 


Name of Sponsor/Company: ImaginAb Inc. 
Name of Study Product: 89Zr-Df-IAB22M2C 
Protocol Number:  
IAB-CD8-201 
Indication: Patients with Selected Advanced and 
Metastatic Solid Tumors including Melanoma, Non-
Small Cell Lung Cancer, Renal Cell Carcinoma, 
Squamous Cell Carcinoma of the Head and Neck, 
Colorectal Cancer-MSI high, Triple Negative Breast, 
Bladder, Cervical, and Esophagogastric Cancers 
• 
Correlation of the 89Zr-Df-IAB22M2C (CD8 PET Tracer) uptake on a subset of PETbaseline and PETtx scans 
that have been virtually reconstructed with lower theoretical doses of 89Zr-Df-IAB22M2C (CD8 PET 
Tracer) with CD8+ cells from IHC analysis. 
Safety Assessments: 
• 
Incidence of Treatment-Emergent Adverse Events (AEs). 
• 
Incidence of withdrawals due to AEs. 
• 
Change/shifts in laboratory values. 
• 
Change in vital signs. 
• 
Change in Electrocardiogram (ECG) parameters. 
• 
Anti-Drug Antibodies 
• 
Serious Adverse Events (SAEs) 
Trial Design:  
• 
Eligible subjects who meet Inclusion/Exclusion criteria will receive 89Zr-Df-IAB22M2C (CD8 PET 
Tracer) as an IV infusion within 1 week prior to the onset of immunotherapy, and 4 to 6 weeks after start 
of immunotherapy. 
• 
Conventional CT Chest, Abdomen and Pelvis (including Neck for SCCHN subjects) or MRI or whole 
body 18FDG-PET scan will be performed within 45 days prior to 1st infusion of 89Zr-Df-IAB22M2C (CD8 
PET Tracer). 
• 
Fresh tumor biopsy ( Preferred3 to 5 core biopsies) will be performed at: 
o 
 Baseline: within -28 to -7 days prior to 1st infusion or 0-6 days after 1st infusion of 89Zr-Df-
IAB22M2C (CD8 PET Tracer) and its associated PET/CT scan of 89Zr-Df-IAB22M2C (CD8 
PET Tracer) at 24hrs post injection.  
o 
Within 2 weeks after 2nd infusion of 89Zr-Df-IAB22M2C (CD8 PET Tracer) and its associated 
PET/CT scan at 24 hrs post injection.  
o 
Archival tumor biopsy tissues obtained within 2 months (60 days) prior to 1st infusion of 89Zr-
Df-IAB22M2C (CD8 PET Tracer) may be submitted in place of Baseline fresh biopsy, with 
approval from the Sponsor.  
• 
PET/CT scans (PETbaseline and PETTx) will be obtained at 24 ± 3 hours after each infusion of  
89Zr-Df-IAB22M2C (CD8 PET Tracer). 
• 
Anti-drug antibody (ADA) blood samples will be collected at the following time points: at Baseline, prior 
to receiving the 2nd infusion of 89Zr-Df-IAB22M2C (CD8 PET Tracer), and at End-of-Study safety 
follow-up visit. 
• 
Safety follow-up: 4-6 weeks after the last dose of 89Zr-Df-IAB22M2C (CD8 PET Tracer). 
• 
Extended follow-up: collect Standard of Care (SOC) imaging only, up to 12 months after start of 
immunotherapy. 
The detailed study schedule and assessments in each visit are provided in Section Error! Reference 
source not found. of the protocol. 
Tumor Biopsy:  
• 
Fresh tumor biopsy from a RECIST 1.1 measurable lesion (excluding cutaneous lesions) within   -28 to -
7 days prior to 1st infusion immunotherapy or 1 to 6 days after 1st infusion of 89Zr-Df-IAB22M2C (CD8 


Name of Sponsor/Company: ImaginAb Inc. 
Name of Study Product: 89Zr-Df-IAB22M2C 
Protocol Number:  
IAB-CD8-201 
Indication: Patients with Selected Advanced and 
Metastatic Solid Tumors including Melanoma, Non-
Small Cell Lung Cancer, Renal Cell Carcinoma, 
Squamous Cell Carcinoma of the Head and Neck, 
Colorectal Cancer-MSI high, Triple Negative Breast, 
Bladder, Cervical, and Esophagogastric Cancers 
PET Tracer) and its associated PET/CT scan; and within 2 weeks after 2nd infusion of 89Zr-Df-IAB22M2C 
(CD8 PET Tracer) and its associated PET/CT scan.  
• 
If biopsy will be performed after the PET/CT scan (either Baseline or On-treatment), image guided biopsy 
will be the preferred method, where the lesion is chosen based on CD8+ PET signal on the CD8 PET/CT 
scan. 
• 
The need for the Baseline biopsy will be considered on a case by case basis following discussion with the 
Sponsor. 
• 
If a patient has had a diagnostic biopsy within 2 months (60 days) prior to the 1st infusion of 89Zr-Df-
IAB22M2C (CD8 PET Tracer), the archival tissue can be submitted for IHC analysis, with approval of 
the Sponsor, provided the specimen is of adequate quality and the biopsy was obtained from a lesion that 
is RECIST 1.1 measurable and remains visible on conventional imaging with CT/MRI. If these conditions 
are met, then the patient can be exempt from the Baseline biopsy. 
• 
Archival tumor tissue must have been obtained after last systemic therapy. The lesion from which the 
archival tissue is obtained should not have received radiation post-biopsy. 
• 
For the 2nd biopsy (within 2 weeks after 2nd infusion of 89Zr-Df-IAB22M2C [CD8 PET Tracer] and 
PET/CT scan), optional surgical resection may be performed in place of biopsy if investigator determines 
the tumor as resectable. 
• 
Assuming a correlation between Tumor SUVmax to SUVmean Aorta reference tissues and CD8+  cell 
measurements by IHC of 0.65, 47 patients will be needed to obtain a width of 0.30. The 95% confidence 
interval is 0.47-0.78, which would be in the range of a good correlation. 


Name of Sponsor/Company: ImaginAb Inc. 
Name of Study Product: 89Zr-Df-IAB22M2C 
Protocol Number:  
IAB-CD8-201 
Indication: Patients with Selected Advanced and 
Metastatic Solid Tumors including Melanoma, Non-
Small Cell Lung Cancer, Renal Cell Carcinoma, 
Squamous Cell Carcinoma of the Head and Neck, 
Colorectal Cancer-MSI high, Triple Negative Breast, 
Bladder, Cervical, and Esophagogastric Cancers 
Inclusion Criteria:  
Subjects will be eligible for enrollment in the study only if they meet ALL of the following criteria: 
1. Patients with advanced or metastatic solid tumors including Melanoma, Non-Small Cell Lung Cancer, 
Renal Cell Carcinoma, Squamous Cell Carcinoma of the Head and Neck,  Colorectal Cancer (MSI-High) 
Triple Negative Breast, Bladder, Cervical and Esophagogastric cancers selected to receive standard-of-
care immunotherapy only, as single agent or in combination. 
2. Patients with at least one non-irradiated lesion:  
• 
At least 1 non-irradiated 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 and non-bone lesion that is accessible, per investigator’s 
assessment, and eligible for biopsy. If only a single RECIST 1.1 measurable lesion is present, 
investigator to determine if the tumor biopsy could interfere with RECIST 1.1 assessments 
of response. 
3. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2. 
4. Meeting all clinical safety lab values per institution’s standard of care, or Investigator’s discretion, for 
patients receiving cancer treatment. 
5. Age ≥ 18 years. 
6. Ability to understand the purposes and risks of the trial and has signed an IRB-approved informed consent 
form.  
7. Willingness and ability to comply with all protocol required procedures. 
8. 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: 
1. Serious nonmalignant disease or conditions that in the opinion of the Investigator and/or ImaginAb could 
compromise protocol objectives. 
2. Patients with a single RECIST 1.1 measurable lesion for biopsy of which, per Investigator’s assessment, 
is likely to interfere with RECIST 1.1 assessments of response. 
3. Patients who have any splenic disorders, or had splenectomy, that in the opinion of the Investigator and/or 
ImaginAb could compromise protocol objectives. 
4. Pregnant women or nursing mothers. 
5. Life expectancy < 6 months 


Statistical Considerations:  
All collected study data will be presented in subject data listings. Statistical analyses will be performed using 
SAS® for Windows, version 9.4 or later. Descriptive statistics (n, mean, standard deviation, median, minimum 
and maximum) will be presented for continuous variables. Frequencies and percentages will be presented for 
categorical variables.  
Sample Size Determination and Rationale 
The sample size calculation is based on the co-primary outcome measure of correlation of 89Zr-Df-IAB22M2C 
(CD8 PET Tracer) uptake as determined by Tumor SUVmax to SUVmean Aorta reference tissue with CD8+ 
cell measurement as determined by IHC from biopsied lesions. Since there are no validated comparator studies 
or imaging scans that can serve as reference values scans for CD8+ cell count, the objective of this study is to 
estimate the correlation between CD8+ cells and quantitative uptake by PET with sufficient precision. 
The objective is to estimate the Spearman’s correlation coefficient with a 0.30 width (width of the 95% 
confidence interval calculated based on Bonett and Wright (2000) method). The sample size is adjusted for 
intra-patient correlation assuming two observations per patient (baseline and on-treatment) and a moderate 
intra-patient correlation of 0.30 (plausible as patients will receive treatment between the two observations). 
Assuming a correlation between Tumor SUVmax to SUVmean Aorta reference tissue and CD8+ cell 
measurements of 0.65, 47 patients will be needed to obtain a width of 0.30. The 95% confidence interval is 
0.47-0.78, which would be in the range of a good correlation. If the estimated correlation is 0.75, the 95% 
confidence interval becomes 0.61-0.85 (width = 0.24). If the estimated correlation is 0.50, the 95% confidence 
interval becomes 0.29-0.66 (width = 0.37). 
 
Analysis Populations 
Efficacy population 
The efficacy population is defined as all subjects who have received at least one dose of study imaging agent 
and have at least one CD8 PET scan of adequate quality and corresponding core biopsy samples of adequate 
quality from at least one location.  
For correlating treatment-related change in PET signal with change in CD8+ cell measurements on IHC: 
Efficacy population is defined as all subjects who have paired Baseline and On-treatment CD8 PET scans and 
corresponding paired biopsy samples.  
Per Protocol (PP) Population 
The Per Protocol (PP) population is defined as the set of subjects who meet the efficacy population 
requirements and were not associated with a major protocol violation. This population will be identified before 
the database lock.   
Safety Population 
The Safety population is defined as all subjects receiving at least one dose of the study imaging agent.  
Analysis Methods:  
The primary analysis of the primary and secondary outcome measures will be conducted using the PP 
population. Analyses of safety outcomes will be conducted using safety population. 
Safety Analysis: 
Analyses of safety outcomes will be conducted using the safety population.  
 
Adverse events will be coded using MedDRA. Treatment Emergent AE’s (TEAE) are defined as events with 
an onset on or after the first treatment. TEAEs will be summarized by treatment group and by stage of the 
study, System Organ Class, and preferred term. The following TEAE summaries will be provided: 
• 
TEAEs by severity grade 
• 
TEAEs by relationship to study treatment. 


Name of Sponsor/Company: ImaginAb Inc. 
Name of Study Product: 89Zr-Df-IAB22M2C 
Protocol Number:  
IAB-CD8-201 
Indication: Patients with Selected Advanced and 
Metastatic Solid Tumors including Melanoma, Non-
Small Cell Lung Cancer, Renal Cell Carcinoma, 
Squamous Cell Carcinoma of the Head and Neck, 
Colorectal Cancer-MSI high, Triple Negative Breast, 
Bladder, Cervical, and Esophagogastric Cancers 
In addition, separate summaries of serious adverse events, and adverse events resulting in discontinuation of 
study treatment will be presented. 
The first co-primary objective is the evaluation of the safety of repeat doses of 89Zr-Df-IAB22M2C (CD8 PET 
Tracer). Adverse events will be graded using CTCAEv5. All grades will be tabulated overall and by injection 
number (1st injection vs 2nd injection). Considering that the safety profile of one dose has been established 
before, no severe (grade ≥3) events are expected, but safety will be closely monitored and safety data will be 
reviewed by a data safety committee. 
In addition, all the data from physical examination, 12-Lead ECG, Serum chemistry, hematology, and vital 
signs will also be descriptively summarized. 
Efficacy Analysis:  
The primary analysis of the primary and secondary outcome measures will be conducted using the PP 
population. 
For the efficacy outcome measures, the data will be summarized and compared according to the variable type.  
Continuous data summaries will include:  
• 
Descriptive summary of number of observations, mean, standard deviation, median, 1st and 3rd quartile 
and minimum and maximum values.  
• 
Inferential statistics include: 
o 
Pearson correlations  
o 
T-test or ANCOVA using the baseline value as a covariate, if the Normality assumption is 
met 
o 
non-parametric or rank based analysis, if the Normality assumption is not met. 
Categorical data summaries will include: 
• Frequency counts and percentages.  
• Chi square test or Logit model for inferential statistics. 
 
To establish the relationship of the PET/CT uptake with CD8+ cells (the second co-primary objective), the 
main analysis will be the Spearman’s correlation coefficient between Tumor SUVmax to Aorta reference tissue 
and CD8+ cells value at all times (baseline and post-treatment). The correlation will then be estimated using 
SUVpeak, SUVmean, CD8 tumor volume (defined as the volume of tumor tissue with SUV > 40% of 
SUVmax), and other tumor: reference ratio. The correlation will be given with a two-sided 95% confidence 
interval accounting for clustering with subjects as clusters (as most subjects will have measurements at 2 
times). Those analyses will be repeated separately at baseline and post-treatment as exploratory analyses. 
The first 15 to 20 patients might be described during the study in order to check the technical quality of the 
data and the imaging. This description will not allow for stopping the trial, no statistical inference will be done, 
and therefore no type-I error is spent at this stage.