A novel tracer shows promise for detecting CD8 T-cells in advanced solid tumors

WASHINGTON – Positron emission tomography (PET) using the CD8-tracer ⁸⁹Zr-IAB22M2C was safe and provided detailed whole-body information on the biodistribution of CD8 T-cells in advanced solid tumors and reference tissue in an open-label, phase 1, first-in-human study.

The findings demonstrate the ability of the tracer–an anti-CD8 zirconium-labeled minibody–to noninvasively detect CD8 distribution in patients with metastatic solid tumors, potentially providing more information – and more quickly – than is possible with a single biopsy, Michael S. Gordon, MD, reported during a late-breaking abstract session at the annual meeting of the Society for Immunotherapy of Cancer.

During a dose escalation period (stage 1) of the study, six patients received 3 mCi of ⁸⁹Zr-IAB22M2C once intravenously followed by serial PET scans over a period of 5-7 days. The patients received increasing protein doses of 0.2 through 10 mg to establish safety and determine a “recommended protein dose and scanning parameters for subsequent trials,” explained Dr. Gordon of HonorHealth Research Institute, Scottsdale, Ariz.

Stage 1 was followed by a dose expansion period (stage 2) in which an additional nine subjects were scanned to better delineate the recommended phase 2 study dose, he said.

All patients were monitored for drug-related adverse events and evaluated with blood chemistry, hematology, cytokine assay, and anti-drug antibodies. Biodistribution, radiodosimetry and semi-quantitative evaluation of CD8-tracer uptake were performed in all patients.

“We saw rapid clearance with excretion through the hepatobiliary mechanism, uptake in T-cell rich tissues, and no uptake in background normal tissues – so no uptake in muscle, heart, brain, or lungs,” he said, adding that “tumor uptake was variable and was clearly seen in 10 out of 15 patients.

“The protein dose that was considered to have favorable biodistribution was the range between 0.5 and 1.5, and based upon the analysis, the most favorable imaging time point ... was deemed to be 24 hours,” he said, noting that changes could be seen in as early as 6 hours.

 

The estimated mean effective radiation dose was 2.4 rem/mCi, “which is consistent with other zirconium-labeled antibody or minibody technologies,” Dr. Gordon said.

Study subjects ranged in age from 31 to 82 years and included nine men and six women with solid tumor malignancies who were eligible to receive checkpoint inhibitor therapy. Their primary cancer types were melanoma (eight patients), non–small-cell lung cancer (six patients), and hepatocellular carcinoma (one patient).

Two patients had received no prior treatment, three had discontinued prior checkpoint inhibitor therapy, and 10 were on immunotherapy.

No drug-related adverse events occurred during the course of the study, although one patient had a transient increase in anti-drug antibodies, Dr. Gordon said.

“Immunotherapy, and specifically checkpoint inhibitors (CPIs), have transformed the landscape of cancer care. Antitumor activity of CPIs is mediated by the CD8-positive T-cell cytotoxic effects, with preclinical and translational clinical studies demonstrating the importance of activated CD8-positive cells within the tumor microenvironment,” he explained, adding that currently available technology is limited in its ability to continually assess the presence of and change in the CD8 infiltrate; one biopsy may fail to capture the immunologic heterogeneity that exists among various tumors in an individual patient.

“As CPI therapy moves into front-line and earlier settings, the ability to have a noninvasive technology to assess whole body and intratumoral changes in CD8 trafficking or expansion in response to therapy is viewed as being crucial,” he said.

A phase 2 study to look closer at the potential for PET + ⁸⁹Zr-IAB22M2C to fulfill that role will begin soon. The study will focus on correlating imaging with synchronous biopsies before and after primary immunotherapy to look for any predictive potential for this technology, he said.

This study was supported by ImaginAb and Parker Institute for Cancer Immunotherapy. Dr. Gordon reported having no disclosures.

SOURCE: Gordon M et al., SITC 2018: Abstract LB49.

WASHINGTON – Positron emission tomography (PET) using the CD8-tracer ⁸⁹Zr-IAB22M2C was safe and provided detailed whole-body information on the biodistribution of CD8 T-cells in advanced solid tumors and reference tissue in an open-label, phase 1, first-in-human study.

The findings demonstrate the ability of the tracer–an anti-CD8 zirconium-labeled minibody–to noninvasively detect CD8 distribution in patients with metastatic solid tumors, potentially providing more information – and more quickly – than is possible with a single biopsy, Michael S. Gordon, MD, reported during a late-breaking abstract session at the annual meeting of the Society for Immunotherapy of Cancer.

During a dose escalation period (stage 1) of the study, six patients received 3 mCi of ⁸⁹Zr-IAB22M2C once intravenously followed by serial PET scans over a period of 5-7 days. The patients received increasing protein doses of 0.2 through 10 mg to establish safety and determine a “recommended protein dose and scanning parameters for subsequent trials,” explained Dr. Gordon of HonorHealth Research Institute, Scottsdale, Ariz.

Stage 1 was followed by a dose expansion period (stage 2) in which an additional nine subjects were scanned to better delineate the recommended phase 2 study dose, he said.

All patients were monitored for drug-related adverse events and evaluated with blood chemistry, hematology, cytokine assay, and anti-drug antibodies. Biodistribution, radiodosimetry and semi-quantitative evaluation of CD8-tracer uptake were performed in all patients.

“We saw rapid clearance with excretion through the hepatobiliary mechanism, uptake in T-cell rich tissues, and no uptake in background normal tissues – so no uptake in muscle, heart, brain, or lungs,” he said, adding that “tumor uptake was variable and was clearly seen in 10 out of 15 patients.

“The protein dose that was considered to have favorable biodistribution was the range between 0.5 and 1.5, and based upon the analysis, the most favorable imaging time point ... was deemed to be 24 hours,” he said, noting that changes could be seen in as early as 6 hours.

 

The estimated mean effective radiation dose was 2.4 rem/mCi, “which is consistent with other zirconium-labeled antibody or minibody technologies,” Dr. Gordon said.

Study subjects ranged in age from 31 to 82 years and included nine men and six women with solid tumor malignancies who were eligible to receive checkpoint inhibitor therapy. Their primary cancer types were melanoma (eight patients), non–small-cell lung cancer (six patients), and hepatocellular carcinoma (one patient).

Two patients had received no prior treatment, three had discontinued prior checkpoint inhibitor therapy, and 10 were on immunotherapy.

No drug-related adverse events occurred during the course of the study, although one patient had a transient increase in anti-drug antibodies, Dr. Gordon said.

“Immunotherapy, and specifically checkpoint inhibitors (CPIs), have transformed the landscape of cancer care. Antitumor activity of CPIs is mediated by the CD8-positive T-cell cytotoxic effects, with preclinical and translational clinical studies demonstrating the importance of activated CD8-positive cells within the tumor microenvironment,” he explained, adding that currently available technology is limited in its ability to continually assess the presence of and change in the CD8 infiltrate; one biopsy may fail to capture the immunologic heterogeneity that exists among various tumors in an individual patient.

“As CPI therapy moves into front-line and earlier settings, the ability to have a noninvasive technology to assess whole body and intratumoral changes in CD8 trafficking or expansion in response to therapy is viewed as being crucial,” he said.

A phase 2 study to look closer at the potential for PET + ⁸⁹Zr-IAB22M2C to fulfill that role will begin soon. The study will focus on correlating imaging with synchronous biopsies before and after primary immunotherapy to look for any predictive potential for this technology, he said.

This study was supported by ImaginAb and Parker Institute for Cancer Immunotherapy. Dr. Gordon reported having no disclosures.

SOURCE: Gordon M et al., SITC 2018: Abstract LB49.

WASHINGTON – Positron emission tomography (PET) using the CD8-tracer ⁸⁹Zr-IAB22M2C was safe and provided detailed whole-body information on the biodistribution of CD8 T-cells in advanced solid tumors and reference tissue in an open-label, phase 1, first-in-human study.

The findings demonstrate the ability of the tracer–an anti-CD8 zirconium-labeled minibody–to noninvasively detect CD8 distribution in patients with metastatic solid tumors, potentially providing more information – and more quickly – than is possible with a single biopsy, Michael S. Gordon, MD, reported during a late-breaking abstract session at the annual meeting of the Society for Immunotherapy of Cancer.

During a dose escalation period (stage 1) of the study, six patients received 3 mCi of ⁸⁹Zr-IAB22M2C once intravenously followed by serial PET scans over a period of 5-7 days. The patients received increasing protein doses of 0.2 through 10 mg to establish safety and determine a “recommended protein dose and scanning parameters for subsequent trials,” explained Dr. Gordon of HonorHealth Research Institute, Scottsdale, Ariz.

Stage 1 was followed by a dose expansion period (stage 2) in which an additional nine subjects were scanned to better delineate the recommended phase 2 study dose, he said.

All patients were monitored for drug-related adverse events and evaluated with blood chemistry, hematology, cytokine assay, and anti-drug antibodies. Biodistribution, radiodosimetry and semi-quantitative evaluation of CD8-tracer uptake were performed in all patients.

“We saw rapid clearance with excretion through the hepatobiliary mechanism, uptake in T-cell rich tissues, and no uptake in background normal tissues – so no uptake in muscle, heart, brain, or lungs,” he said, adding that “tumor uptake was variable and was clearly seen in 10 out of 15 patients.

“The protein dose that was considered to have favorable biodistribution was the range between 0.5 and 1.5, and based upon the analysis, the most favorable imaging time point ... was deemed to be 24 hours,” he said, noting that changes could be seen in as early as 6 hours.

 

The estimated mean effective radiation dose was 2.4 rem/mCi, “which is consistent with other zirconium-labeled antibody or minibody technologies,” Dr. Gordon said.

Study subjects ranged in age from 31 to 82 years and included nine men and six women with solid tumor malignancies who were eligible to receive checkpoint inhibitor therapy. Their primary cancer types were melanoma (eight patients), non–small-cell lung cancer (six patients), and hepatocellular carcinoma (one patient).

Two patients had received no prior treatment, three had discontinued prior checkpoint inhibitor therapy, and 10 were on immunotherapy.

No drug-related adverse events occurred during the course of the study, although one patient had a transient increase in anti-drug antibodies, Dr. Gordon said.

“Immunotherapy, and specifically checkpoint inhibitors (CPIs), have transformed the landscape of cancer care. Antitumor activity of CPIs is mediated by the CD8-positive T-cell cytotoxic effects, with preclinical and translational clinical studies demonstrating the importance of activated CD8-positive cells within the tumor microenvironment,” he explained, adding that currently available technology is limited in its ability to continually assess the presence of and change in the CD8 infiltrate; one biopsy may fail to capture the immunologic heterogeneity that exists among various tumors in an individual patient.

“As CPI therapy moves into front-line and earlier settings, the ability to have a noninvasive technology to assess whole body and intratumoral changes in CD8 trafficking or expansion in response to therapy is viewed as being crucial,” he said.

A phase 2 study to look closer at the potential for PET + ⁸⁹Zr-IAB22M2C to fulfill that role will begin soon. The study will focus on correlating imaging with synchronous biopsies before and after primary immunotherapy to look for any predictive potential for this technology, he said.

This study was supported by ImaginAb and Parker Institute for Cancer Immunotherapy. Dr. Gordon reported having no disclosures.

SOURCE: Gordon M et al., SITC 2018: Abstract LB49.