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

Positron-Emission Tomography Clinical Trial

— iCorrelate  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03802123
• Other study ID #: IAB-CD8-201
• Status: Completed
• Phase: Phase 2
• Start date: December 18, 2018
• Est. completion date: July 18, 2022

Study information

• Verified date: November 2022
• Source: ImaginAb, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 52
• Est. completion date: July 18, 2022
• Est. primary completion date: October 19, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Metastatic Solid Tumors
• Positron-Emission Tomography

Intervention

Drug:
• 8?Zr-Df-IAB22M2C
8?Zr-Df-IAB22M2C CD8 T cell tracer for Positron Emission Tomography (PET)

Locations

Country	Name	City	State
United States	University of Alabama-Birmingham Hospital	Birmingham	Alabama
United States	Dana-Farber Cancer Institute (DFCI)	Boston	Massachusetts
United States	Karmanos Cancer Institute	Detroit	Michigan
United States	City of Hope (City of Hope National Medical Center, City of Hope Medical Center)	Duarte	California
United States	University of Iowa Hospitals and Clinics	Iowa City	Iowa
United States	CARTI Cancer Center	Little Rock	Arkansas
United States	Keck Hospital of USC	Los Angeles	California
United States	LAC + USC Medical Center	Los Angeles	California
United States	USC/Norris Comprehensive Cancer Center	Los Angeles	California
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Hoag Memorial Hospital Presbyterian	Newport Beach	California
United States	University of Pennsylvania, Perelman School of Medicine	Philadelphia	Pennsylvania
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	John Wayne Cancer Institute at Providence Saint John's Health Center	Santa Monica	California
United States	Seattle Cancer Care Alliance/ University of Washington	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
ImaginAb, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Evaluation of the variance in gene expression profiles in subjects prior to and On-treatment as measured in whole blood by Nanostring analysis.	Evaluation of the variance in gene expression profiles in subjects prior to and On-treatment as measured in whole blood by Nanostring analysis.	7 weeks
Other	Correlation of visual and quantitative 8?Zr-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.	Correlation of visual and quantitative 8?Zr-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.	7 weeks
Other	Estimation of positive predictive value, negative predictive value, sensitivity and specificity of 8?Zr-Df-IAB22M2C (CD8 PET Tracer) PET for detecting CD8+ T cells as determined by IHC.	Estimation of positive predictive value, negative predictive value, sensitivity and specificity of 8?Zr-Df-IAB22M2C (CD8 PET Tracer) PET for detecting CD8+ T cells as determined by IHC.	7 weeks
Other	Assessment of changes in 8?Zr-Df-IAB22M2C (CD8 PET Tracer) uptake and distribution from baseline to 5-7 days start of immunotherapy if available.	Assessment of changes in 8?Zr-Df-IAB22M2C (CD8 PET Tracer) uptake and distribution from baseline to 5-7 days start of immunotherapy if available.	7 weeks
Other	Correlation of 8?Zr-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 8?Zr-Df-IAB22M2C (CD8 PET Tracer) uptake with clinical outcomes	18 months
Other	Correlation of 8?Zr-Df-IAB22M2C (CD8 PET Tracer) uptake with radiologic responses	Correlation of 8?Zr-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 weeks
Other	Correlation of 8?Zr-Df-IAB22M2C (CD8 PET Tracer) tumor and lymph node uptake with immune infiltrates and other molecular biomarker (CD8) expression by IHC	Correlation of 8?Zr-Df-IAB22M2C (CD8 PET Tracer) tumor and lymph node uptake with immune infiltrates and other molecular biomarker (CD8) expression by IHC	7 weeks
Other	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 88?Zr-Df-IAB22M2C (CD8 PET Tracer) with CD8+ T cells from IHC analysis.	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 88?Zr-Df-IAB22M2C (CD8 PET Tracer) with CD8+ T cells from IHC analysis.	7 weeks
Primary	Correlation of 8?Zr-Df-IAB22M2C uptake in biopsied tumors with CD8+ cell measurement by immunohistochemistry (IHC)	Analyze 8?Zr-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
Primary	Adverse events	The incident and severity of adverse events per CTCAE criteria will be recorded following repeat doses of 8?Zr-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 8?Zr-Df-IAB22M2C (Visit 2 Day 1) through 4-5 weeks after the second infusion of 8?Zr-Df-IAB22M2C
Primary	Signs and symptoms of infusion reactions	Signs and symptoms of infusion reactions following repeat doses of 8?Zr-Df-IAB22M2C will be assessed evaluating the incidence and severity of local and systemic signs and symptoms of infusion reactions	Time of infusion of 8?Zr-Df-IAB22M2C (Visit 2 Day 1) through 4-5 weeks after the second infusion of 8?Zr-Df-IAB22M2C
Primary	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 8?Zr-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
Primary	Changes in mean corpscular volume (fL) laboratory values compared to baseline	mean corpscular volume (fL) laboratory values compared with baseline results.	prior to infusion 8?Zr-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
Primary	Changes in hematocrit (%) laboratory values compared with baseline	hematocrit (%) laboratory values compared with baseline results.	prior to infusion 8?Zr-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
Primary	Changes in hemoglobin (g/dL) laboratory values compared with baseline	hemoglobin (g/dL) laboratory values compared with baseline results.	prior to infusion 8?Zr-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
Primary	Changes in platelet count (thousands/ul) laboratory values compared with baseline	platelet count (thousands/ul) laboratory values compared with baseline results.	prior to infusion 8?Zr-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
Primary	Changes in WBC count (thousands/ul) laboratory values compared with baseline	WBC count (thousands/ul) laboratory values compared with baseline results.	prior to infusion 8?Zr-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
Primary	Changes in RBC count (millions/uL) laboratory values compared with baseline	RBC count (millions/uL) laboratory values compared with baseline results.	prior to infusion 8?Zr-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
Primary	Changes in blood glucose (mg/dL) laboratory values compared with baseline	blood glucose (mg/dL) laboratory values compared with baseline results.	prior to infusion 8?Zr-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
Primary	Changes in chloride (mmol/L) laboratory values compared with baseline	chloride (mmol/L) laboratory values compared with baseline results.	prior to infusion 8?Zr-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
Primary	Changes in potassium (mmol/L) laboratory values compared with baseline	Potassium (mmol/L) laboratory values compared with baseline results.	prior to infusion 8?Zr-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
Primary	Changes in sodium (mmol/L) laboratory values compared with baseline	sodium (mmol/L) laboratory values compared with baseline results.	prior to infusion 8?Zr-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
Primary	Changes in uric acid (mg/dL) laboratory values compared with baseline	uric acid (mg/dL) laboratory values compared with baseline results.	prior to infusion 8?Zr-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
Primary	Changes in serum creatinine (mg/dL) laboratory values compared with baseline	serum creatinine (mg/dL) laboratory values compared with baseline results.	prior to infusion 8?Zr-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
Primary	Changes in GGT (U/L) laboratory values compared with baseline	GGT (U/L) laboratory values compared with baseline results.	prior to infusion 8?Zr-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
Primary	Changes in BUN (mg/dL) laboratory values compared with baseline	BUN (mg/dL) laboratory values compared with baseline results.	prior to infusion 8?Zr-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
Primary	Changes in LDH (U/L) laboratory values comapared with baseline	LDH (U/L) laboratory values compared with baseline results.	prior to infusion 8?Zr-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
Primary	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 8?Zr-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
Primary	ALP laboratory values	Change/shifts in ALP (U/L) laboratory values compared with baseline results.	prior to infusion 8?Zr-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
Primary	ALT laboratory values	Change/shifts in ALT (U/L) laboratory values compared with baseline results.	prior to infusion 8?Zr-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
Primary	AST laboratory values	Change/shifts in AST (U/L) laboratory values compared with baseline results.	prior to infusion 8?Zr-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
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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	Assessment of Baseline and On-treatment 8?Zr-Df-IAB22M2C uptake and distribution in tumors and lymphoid organs, and measurement of change between the paired observations	Assessment of Baseline and On-treatment 8?Zr-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 8?Zr-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
Secondary	Measurement of change in 8?Zr-Df-IAB22M2C (CD8 PET Tracer) uptake in biopsied tumors as determined by SUV-based quantitative analysis	Measurement of change in 8?Zr-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
Secondary	Description of biodistribution patterns of 8?Zr-Df-IAB22M2C (CD8 PET Tracer) on PETbaseline and PETTx and any changes in biodistribution between baseline and On-Treatment.	Description of biodistribution patterns of 8?Zr-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