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

• ClinicalTrials.gov Identifier: NCT03802123
• Recruitment Status: Completed
• First Posted: January 14, 2019
• Last Update Posted: November 17, 2022
• Sponsor: ImaginAb, Inc.
• Information provided by (Responsible Party): ImaginAb, Inc.

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Positron-Emission Tomography; Metastatic Solid Tumors	Drug: ⁸⁹Zr-Df-IAB22M2C	Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 52 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: 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
• Actual Study Start Date: December 18, 2018
• Actual Primary Completion Date: October 19, 2021
• Actual Study Completion Date: July 18, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: ⁸⁹Zr-Df-IAB22M2C Infusion; 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; ⁸⁹Zr-Df-IAB22M2C CD8 T cell tracer for Positron Emission Tomography (PET)

Outcome Measures

Primary Outcome Measures :

1. Correlation of ⁸⁹Zr-Df-IAB22M2C uptake in biopsied tumors with CD8+ cell measurement by immunohistochemistry (IHC) [ Time Frame: Baseline to 4-5 weeks after the start of immunotherapy ]
   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.
2. Adverse events [ Time Frame: Time of infusion of ⁸⁹Zr-Df-IAB22M2C (Visit 2 Day 1) through 4-5 weeks after the second infusion of ⁸⁹Zr-Df-IAB22M2C ]
   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.
3. Signs and symptoms of infusion reactions [ Time Frame: 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 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
4. Change in WBC differential including percentages of total WBC and absolute counts: (neutrophils, immature neutrophils, lymphocytes, monocytes, eosinophils, basophils) laboratory values compared to baseline [ Time Frame: 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 ]
   WBC differential including percentages of total WBC and absolute counts: (neutrophils, immature neutrophils, lymphocytes, monocytes, eosinophils, basophils) laboratory values compared with baseline results.
5. Changes in mean corpscular volume (fL) laboratory values compared to baseline [ Time Frame: 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 ]
   mean corpscular volume (fL) laboratory values compared with baseline results.
6. Changes in hematocrit (%) laboratory values compared with baseline [ Time Frame: 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 ]
   hematocrit (%) laboratory values compared with baseline results.
7. Changes in hemoglobin (g/dL) laboratory values compared with baseline [ Time Frame: 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 ]
   hemoglobin (g/dL) laboratory values compared with baseline results.
8. Changes in platelet count (thousands/ul) laboratory values compared with baseline [ Time Frame: 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 ]
   platelet count (thousands/ul) laboratory values compared with baseline results.
9. Changes in WBC count (thousands/ul) laboratory values compared with baseline [ Time Frame: 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 ]
   WBC count (thousands/ul) laboratory values compared with baseline results.
10. Changes in RBC count (millions/uL) laboratory values compared with baseline [ Time Frame: 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 ]
    RBC count (millions/uL) laboratory values compared with baseline results.
11. Changes in blood glucose (mg/dL) laboratory values compared with baseline [ Time Frame: 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 ]
    blood glucose (mg/dL) laboratory values compared with baseline results.
12. Changes in chloride (mmol/L) laboratory values compared with baseline [ Time Frame: 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 ]
    chloride (mmol/L) laboratory values compared with baseline results.
13. Changes in potassium (mmol/L) laboratory values compared with baseline [ Time Frame: 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 ]
    Potassium (mmol/L) laboratory values compared with baseline results.
14. Changes in sodium (mmol/L) laboratory values compared with baseline [ Time Frame: 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 ]
    sodium (mmol/L) laboratory values compared with baseline results.
15. Changes in uric acid (mg/dL) laboratory values compared with baseline [ Time Frame: 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 ]
    uric acid (mg/dL) laboratory values compared with baseline results.
16. Changes in serum creatinine (mg/dL) laboratory values compared with baseline [ Time Frame: 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 ]
    serum creatinine (mg/dL) laboratory values compared with baseline results.
17. Changes in GGT (U/L) laboratory values compared with baseline [ Time Frame: 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 ]
    GGT (U/L) laboratory values compared with baseline results.
18. Changes in BUN (mg/dL) laboratory values compared with baseline [ Time Frame: 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 ]
    BUN (mg/dL) laboratory values compared with baseline results.
19. Changes in LDH (U/L) laboratory values comapared with baseline [ Time Frame: 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 ]
    LDH (U/L) laboratory values compared with baseline results.
20. Bilirubin, direct and total (mg/dL) laboratory values [ Time Frame: 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 ]
    Change/shifts in Bilirubin, direct and total (mg/dL) laboratory values compared with baseline results.
21. ALP laboratory values [ Time Frame: 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 ]
    Change/shifts in ALP (U/L) laboratory values compared with baseline results.
22. ALT laboratory values [ Time Frame: 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 ]
    Change/shifts in ALT (U/L) laboratory values compared with baseline results.
23. AST laboratory values [ Time Frame: 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 ]
    Change/shifts in AST (U/L) laboratory values compared with baseline results.
24. 12-Lead electrocardiogram [ Time Frame: Within 60 minutes post-infusion (study visits 2 and 5) ]
    Proportion of subjects with abnormal electrocardiogram findings prior to and within 1 hour post injection.
25. Evaluation of blood pressure [ Time Frame: 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) ]
    Changes/shifts in blood pressure (systolic and diastolic)
26. Evaluation of heart rate [ Time Frame: 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) ]
    Changes/shifts in heart rate
27. Evaluation of respiration rate [ Time Frame: 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) ]
    Changes/shifts in respiration rate
28. Evaluation of temperature [ Time Frame: 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) ]
    Changes/shifts in temperature

Secondary Outcome Measures :

1. 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 [ Time Frame: 5 weeks ]

   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.
2. Measurement of change in ⁸⁹Zr-Df-IAB22M2C (CD8 PET Tracer) uptake in biopsied tumors as determined by SUV-based quantitative analysis [ Time Frame: 7 weeks ]
   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.
3. 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. [ Time Frame: 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. 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

Other Outcome Measures:

1. Evaluation of the variance in gene expression profiles in subjects prior to and On-treatment as measured in whole blood by Nanostring analysis. [ Time Frame: 7 weeks ]
   Evaluation of the variance in gene expression profiles in subjects prior to and On-treatment as measured in whole blood by Nanostring analysis.
2. Correlation of visual and quantitative ⁸⁹Zr-Df-IAB22M2C (CD8 PET Tracer) uptake in tumor lesions 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. [ Time Frame: 7 weeks ]
   Correlation of visual and quantitative ⁸⁹Zr-Df-IAB22M2C (CD8 PET Tracer) uptake in tumor lesions 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.
3. Estimation of positive predictive value, negative predictive value, sensitivity and specificity of ⁸⁹Zr-Df-IAB22M2C (CD8 PET Tracer) PET for detecting CD8+ T cells as determined by IHC. [ Time Frame: 7 weeks ]
   Estimation of positive predictive value, negative predictive value, sensitivity and specificity of ⁸⁹Zr-Df-IAB22M2C (CD8 PET Tracer) PET for detecting CD8+ T cells as determined by IHC.
4. Assessment of changes in ⁸⁹Zr-Df-IAB22M2C (CD8 PET Tracer) uptake and distribution from baseline to 5-7 days start of immunotherapy if available. [ Time Frame: 7 weeks ]
   Assessment of changes in ⁸⁹Zr-Df-IAB22M2C (CD8 PET Tracer) uptake and distribution from baseline to 5-7 days start of immunotherapy if available.
5. 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. [ Time Frame: 18 months ]
   Correlation of ⁸⁹Zr-Df-IAB22M2C (CD8 PET Tracer) uptake with clinical outcomes
6. Correlation of ⁸⁹Zr-Df-IAB22M2C (CD8 PET Tracer) uptake with radiologic responses [ Time Frame: 7 weeks ]

   Correlation of ⁸⁹Zr-Df-IAB22M2C (CD8 PET Tracer) uptake with radiologic responses based upon:

   • Correlation of subject response by RECIST 1.1 compared to visual and quantitative SUVbased analysis
   • Correlation of RECIST 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.
7. Correlation of ⁸⁹Zr-Df-IAB22M2C (CD8 PET Tracer) tumor and lymph node uptake with immune infiltrates and other molecular biomarker (CD8) expression by IHC [ Time Frame: 7 weeks ]
   Correlation of ⁸⁹Zr-Df-IAB22M2C (CD8 PET Tracer) tumor and lymph node uptake with immune infiltrates and other molecular biomarker (CD8) expression by IHC
8. 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 8⁸⁹Zr-Df-IAB22M2C (CD8 PET Tracer) with CD8+ T cells from IHC analysis. [ Time Frame: 7 weeks ]
   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 8⁸⁹Zr-Df-IAB22M2C (CD8 PET Tracer) with CD8+ T cells from IHC analysis.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

Participants will be eligible for enrollment in the study only if they meet ALL of the following criteria:

1. 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.
2. • 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.
3. 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.
4. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
5. Meeting all clinical safety lab values per institution's standard of care, or Investigator's discretion, for patients receiving cancer treatment.
6. Age ≥ 18 years.
7. Ability to understand the purposes and risks of the trial and has signed an IRB-approved informed consent form.
8. Willingness and ability to comply with all protocol required procedures.
9. 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 measurable lesion, biopsy of which, per investigator's assessment, is likely to interfere with RECIST 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. 5. Life expectancy < 6 months

Contacts and Locations

Locations

United States, Alabama

University of Alabama-Birmingham Hospital

Birmingham, Alabama, United States, 35294

United States, Arkansas

CARTI Cancer Center

Little Rock, Arkansas, United States, 72205

United States, California

City of Hope (City of Hope National Medical Center, City of Hope Medical Center)

Duarte, California, United States, 91010

Keck Hospital of USC

Los Angeles, California, United States, 90033

LAC + USC Medical Center

Los Angeles, California, United States, 90033

USC/Norris Comprehensive Cancer Center

Los Angeles, California, United States, 90033

Hoag Memorial Hospital Presbyterian

Newport Beach, California, United States, 92663

John Wayne Cancer Institute at Providence Saint John's Health Center

Santa Monica, California, United States, 90404

United States, Iowa

University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States, 52242

United States, Massachusetts

Dana-Farber Cancer Institute (DFCI)

Boston, Massachusetts, United States, 02215

United States, Michigan

Karmanos Cancer Institute

Detroit, Michigan, United States, 48201

United States, Missouri

Washington University School of Medicine

Saint Louis, Missouri, United States, 63110

United States, New York

Memorial Sloan Kettering Cancer Center

New York, New York, United States, 10065

United States, Pennsylvania

University of Pennsylvania, Perelman School of Medicine

Philadelphia, Pennsylvania, United States, 19104

United States, Washington

Seattle Cancer Care Alliance/ University of Washington

Seattle, Washington, United States, 98109

Sponsors and Collaborators

ImaginAb, Inc.

Investigators

• Study Director: Ron Korn, MD, PhD; ImaginAb, Inc.

More Information

• Responsible Party: ImaginAb, Inc.
• ClinicalTrials.gov Identifier: NCT03802123
• Other Study ID Numbers: IAB-CD8-201
• First Posted: January 14, 2019
• Last Update Posted: November 17, 2022
• Last Verified: November 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by ImaginAb, Inc.:

PET/CT; ⁸⁹Zr-Df-IAB22M2C; CD8; Imaging