⁸⁹Zr-Df-IAB22M2C PET/CT in Patients With Selected Solid Malignancies or Hodgkin's Lymphoma

A Phase I Study of Positron Emission Tomography (PET/CT) With ⁸⁹Zr-Df-IAB22M2C in Patients With Selected Solid Malignancies (Non Small Cell Lung Cancer (NSCLC), Small Cell Lung Cancer (SCLC), Squamous Cell Carcinoma Head and Neck (SqCCHN), Melanoma, Merkel Cell Tumor, Renal, Bladder, Hepatocellular, Triple Negative Breast, or Gastroesophageal Cancer) or Hodgkin's Lymphoma

To determine the safety and feasibility of 89Zr-Df-IAB22M2C as an immunoPET tracer; determine the best time window and protein dose for imaging; determine the pharmacokinetic (PK) and biodistribution of the probe; and to determine imaging parameters for optimal lymphoid and tumor visualization.

This is a phase I study of positron emission tomography (PET/CT) with ⁸⁹Zr-Df-IAB22M2C in patients with selected solid malignancies (NSCLC, SCLC, SqCCHN, melanoma, merkel cell tumor, renal, bladder, hepatocellular, triple negative breast, or gastroesophageal cancer) or Hodgkin's lymphoma. Up to 24 subjects are planned to be enrolled in this clinical study.

This phase 1 study is a dose escalation study of ⁸⁹Zr-Df-IAB22M2C to evaluate safety, tolerability, optimal time window and protein dose for imaging, biodistribution, radiation dosimetry, as well as the ability of ⁸⁹Zr-Df-IAB22M2C to detect CD8+ expressing T cells. The investigational imaging agent to be administered in this study will be 3.0 (±20%) mCi dose of ⁸⁹Zr-Df-IAB22M2C injected intravenously. Up to six cohorts of up to 6 patients each will be studied sequentially with dose escalation at 0.2 mg, 0.5 mg, 1.0 mg, 1.5 mg, 5.0 mg, and 10.0 mg total protein doses followed by an optimal dose expansion cohort. Safety as well as lymphoid visualization (LV) on imaging (i.e. signal in tumor and lymphoid organs including spleen, lymph nodes and bone marrow) will be evaluated to drive dose escalation/de-escalation.

At least 2 weeks will separate the ⁸⁹Zr-Df-IAB22M2C administration in the first patient and subsequent patients of each dose cohort to provide an opportunity to detect any acute reaction to the study drug and any adverse events. Tracer administration for subsequent patients in each cohort will be separated by a minimum of 24 hours

Each patient will undergo five (5) post infusion PET/CT scans ( 1 - 2 hours, 6-8 hrs (optional), 24 ± 4 hours, 48 ± 4 hours and 92 - 144 hours).

Pharmacokinetic blood samples will be drawn at the following timepoints: pre-infusion; then post-infusion at 5-10 min, 30 (+/-10) min, 60 (+/- 10) min, 120 (+/- 10) min, 240 (+/- 10) min, 350-490 (+/- 10) min (optional), 24 hrs (visit 3), 48 hrs (visit 4), 92-144 hrs (visit 5). The imaging data collected across the dosing cohort and time series of PET/CT scans will assess biodistribution, dosimetry, and be used to recommend a protein dose and an optimal time window for imaging in future studies

Inclusion Criteria:

1. Patients with selected solid malignancies (NSCLC, SCLC, SqCCHN, melanoma, merkel cell tumor, renal, bladder, hepatocellular, triple negative breast, or gastroesophageal cancer) or Hodgkin's lymphoma
2. At least 1 measurable lesion documented on CT/MRI (RECIST criteria 1.1)
3. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Appendix B: ECOG Scoring)
4. Age ≥ 18 years
5. Ability to understand the purposes and risks of the trial and has signed a IRB-approved informed consent form
6. Willingness and ability to comply with all protocol required procedures
7. For men and women of child-bearing potential, use of effective contraceptive methods during the study

Exclusion Criteria:

Patients meeting any of the following criteria will not be eligible for study entry:

1. Known infection with human immunodeficiency virus (HIV)

2. Serious nonmalignant disease or conditions that in the opinion of the investigator and/or ImaginAb could compromise protocol objectives

3. Patients who have had splenectomy.

4. Patients who have any splenic disorders that in the opinion of the investigator and/or ImaginAb could compromise protocol objectives.

5. Patients who are currently receiving any other investigational agent

6. Pregnant women or nursing mothers

7. Hepatic laboratory values:

   1. Bilirubin > 1.5 x ULN (institutional upper limits of normal)
   2. Albumin < 2 g/dL
   3. Other local safety laboratory test results (clinical chemistry and hematology) are determined to be exclusionary by the Investigator.

8. Known sensitivity to glutamic acid or glutamate.