CD8+ PET Companion Trial

• ClinicalTrials.gov Identifier: NCT05279027
• Recruitment Status: Enrolling by invitation
• First Posted: March 15, 2022
• Last Update Posted: June 1, 2022
• Sponsor: Abramson Cancer Center of the University of Pennsylvania
• Collaborator: ImaginAb, Inc.
• Information provided by (Responsible Party): Abramson Cancer Center of the University of Pennsylvania

Study Description

Brief Summary:

Study of 89Zr-Df-IAB22M2C PET/CT as an imaging biomarker for assessing an early response to therapy in patients with advanced melanoma on immunotherapy and hydroxychloroquine. This study is a companion study to the "LIMIT Melanoma Trial." Patients with melanoma who are potentially eligible for the LIMIT Melanoma Trial and have at least one site of measurable disease based on RECIST 1.1 are potentially eligible. Associations with progression-free survival (PFS) and overall survival (OS) will be tested.

Condition or disease	Intervention/treatment	Phase
Melanoma (Skin)	Drug: 89Zr-Df-IAB22M2C PET/CT	Early Phase 1

Detailed Description:

This is a single institution, prospective cohort study of 89Zr-Df-IAB22M2C PET/CT as an early measure of response in patients with melanoma. This study is a companion imaging study to the "LIMIT Melanoma Trial". Patients with melanoma who are candidates for the LIMIT Melanoma treatment trial and are at least 18 years of age may be eligible. All participants will be receiving care at the clinical practices of the University of Pennsylvania. Patients will be approached about study participation regardless of race or ethnic background. We anticipate enrolling up to 20 evaluable participants with melanoma who meet eligibility requirements for this study. An evaluable patient has completed Baseline and at the post-Treatment 89Zr-Df-IAB22M2C PET/CT scans. Accrual is estimated to occur over approximately 3 years.

After undergoing screening assessments and verifying eligibility for study participation subjects will be scheduled to undergo a Baseline 89Zr-Df-IAB22M2C PET/CT scan prior to starting immunotherapy + HCQ therapy. For the Baseline study, subjects will be injected with 89Zr-Df-IAB22M2C up to 8 days prior to starting therapy (Day -8 to 0), and will undergo PET/CT imaging 24 ± 4 hours post injection, and prior to therapy administration. Subjects will then undergo a Post-Treatment 89Zr-Df-IAB22M2C PET/CT scan at day 12 (± 2 days) post therapy, which will require administration of 89Zr-Df-IAB22M2C on the day prior to the scan. 89Zr-Df-IAB22M2C PET/CT scans will be acquired with an interval of ≥ 12 days between scans, to ensure that the signal from the previous injection of 89Zr-Df-IAB22M2C has decayed.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 20 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: 89Zr-Df-IAB22M2C (Anti-CD8 Minibody) PET/CT Imaging as a Measure of Response in Patients With Advanced Melanoma on Immunotherapy Plus Hydroxychloroquine.
• Actual Study Start Date: March 8, 2022
• Estimated Primary Completion Date: December 31, 2024
• Estimated Study Completion Date: February 28, 2025

Arms and Interventions

Arm	Intervention/treatment
Experimental: PET imaging; This is a single institution, prospective cohort study of 89Zr-Df-IAB22M2C PET/CT as an early measure of response in patients with melanoma.	Drug: 89Zr-Df-IAB22M2C PET/CT; 89Zr-Df-IAB22M2C PET/CT scans pre and post therapy initiation

Outcome Measures

Primary Outcome Measures :

1. 89Zr-Df-IAB22M2C uptake [ Time Frame: 21 days ]
   89Zr-Df-IAB22M2C measured uptake *(by standard uptake value) on Baseline and post-Treatment PET/CT scans in tumor lesions and lymphoid organs.
2. Change in uptake post therapy [ Time Frame: 21 days ]
   Measurement of change in 89Zr-Df-IAB22M2C uptake between Baseline and post-Treatment PET/CT scans in tumor lesions and lymphoid organs.

Secondary Outcome Measures :

1. Post therapy outcomes [ Time Frame: until the end of the study, usually about 3 years ]
   Association between change in tumor 89Zr-Df-IAB22M2C uptake and objective response, progression free survival, and overall survival.
2. CD8+ TIL density in tumor [ Time Frame: 2 months ]
   Association between tumor 89Zr-Df-IAB22M2C uptake and CD8+ TIL density in biopsied tumors.

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:

1. Adult patients, at least 18 years of age
2. History of histologically confirmed melanoma as assessed per medical record review.
3. At least one site of measurable disease (per RECIST 1.1) that is seen on CT, MRI, or FDG PET/CT.
4. Potentially eligible to participate in the LIMIT Melanoma Trial.

5. Patients must have adequate baseline organ function as determined per LIMIT Melanoma Trial (IRB 835033) (these tests will be completed as part of LIMIT trial screening and will not be repeated for the imaging companion study)

   Adequate organ function: per LIMIT Melanoma Trial (IRB 35033)

   System Laboratory Values Hematologic Absolute Neutrophil Count (ANC) ≥ 1.0 x 109/L Hemoglobin ≥ 9 g/dL Platelet Count ≥ 100 x 109/L PT/INRa and PTT ≤ 1.3 x ULN Hepatic Total Bilirubinb ≤ 1.5 x ULN AST and ALT ≤ 2.5 x ULN Renal Serum Creatinine ≤ 1.5 mg/dL Abbreviations: ALT = alanine transaminase; ANC = absolute neutrophil count; AST = aspartate aminotransferase; INR = international normalized ratio; LLN = lower limit of normal; PT = prothrombin time; PTT = partial thromboplastin time; ULN = upper limit of normal.

   a Subjects receiving anticoagulation treatment may be allowed to participate with INR established within the therapeutic range prior to enrollment.

   b Subjects with known Gilbert's syndrome must have a total bilirubin < 3.0 x ULN).

   c If serum creatinine is > 1.5 mg/dL, calculate creatinine clearance using standard Cockcroft-Gault formula. Creatinine clearance must be ≥ 50 mL/min to be eligible.

6. Participants must be informed of the investigational nature of this study and provide written informed consent in accordance with institutional and federal guidelines prior to study-specific procedures.

Exclusion Criteria:

1. Females who report they are pregnant or breast-feeding at the time of screening will not be eligible for this study. Female participants of child-bearing potential will have a urine pregnancy test prior to infusion of the study radiotracer to confirm they are not pregnant.
2. Patients who have any splenic disorders, or had splenectomy, that in the opinion of an investigator could compromise protocol objectives.
3. Inability to tolerate imaging procedures in the opinion of the investigator or treating physician.
4. Serious or unstable medical or psychological conditions that, in the opinion of the investigator would compromise the subject's safety or successful participation in the study.
5. Ineligible for the LIMIT Melanoma Trial.

Contacts and Locations

Locations

United States, Pennsylvania

Perleman Center for Advanced Medicine

Philadelphia, Pennsylvania, United States, 19104

Sponsors and Collaborators

Abramson Cancer Center of the University of Pennsylvania

ImaginAb, Inc.

More Information

• Responsible Party: Abramson Cancer Center of the University of Pennsylvania
• ClinicalTrials.gov Identifier: NCT05279027
• Other Study ID Numbers: 844867
• First Posted: March 15, 2022
• Last Update Posted: June 1, 2022
• Last Verified: March 2022

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

Keywords provided by Abramson Cancer Center of the University of Pennsylvania:

Positron Emission Tomography

Additional relevant MeSH terms:

Melanoma; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas