Imaging of Solid Tumors Using FAP-2286

Overview

This is a multi-arm prospective trial that evaluates the ability of a novel imaging radiolabeled agents to detect metastatic cancer in participants with solid tumors using a gallium 68 (68Ga-) or copper 64 (64Cu-) FAP-2286 tracer. FAP-2286 is a peptidomimetic molecule that that binds to Fibroblast Activation Protein (FAP). FAP is a transmembrane protein expressed on cancer-associated fibroblasts, and has been shown to be present on a number of solid tumors.

Detailed description

Initially the investigator(s) will focus on imaging breast, pancreas, sarcoma, prostate cancer, bladder cancer, colon cancer, and head and neck cancer.

STUDY AIMS

1. Determine the dosimetry for gallium-68 labelled (68Ga-) and 64Cu- FAP-2286. 2. Evaluate the uptake and retention of radiotracer in a variety of solid tumors with FAP-2286. 3. Evaluate the ability of FAP-2286 to detect metastatic disease.

PRIMARY OBJECTIVES

1. All cohorts: Safety of 68Ga- and 64Cu-FAP-2286. 2. Cohort 1a: determine the organ dosimetry of 68Ga-FAP-2286. 3. Cohort 1b: determine the organ dosimetry of 64Cu-FAP-2286. 4. Cohort 2: To assess the feasibility of detecting tumor uptake using FAP-2286. 5. Cohort 3: To determine the feasibility of detecting metastatic disease using FAP-2286.

EXPLORATORY OBJECTIVES

1. To detect the sensitivity of FAP-2286 PET compared to conventional imaging for the detection of metastatic disease, and when available sensitivity compared to Fluorodeoxyglucose (FDG) PET (FDG-PET). 2. Correlation of FAP-2286 uptake with FAP expression determined by immunohistochemistry. 3. Compare biodistribution of 68Ga-FAP-2286 and 64Cu-FAP-2286 in normal organs and blood pool based on renal function. 4. Determine impact of administered dose of FAP-2286 on image quality. 5. Compare the feasibility of detecting tumor uptake using 68Ga-FAP-2286 and 64Cu-FAP-2286

A repeat radiolabeled FAP-2286 PET may be obtained after initiation of subsequent treatment in order to evaluate changes in PET uptake due to treatment effect. Participants will be followed through the day of the last injection of radiolabeled FAP-2286 for evaluation of adverse events.

Interventions

• Drug Gallium-68 labelled (68Ga-) FAP-2286
  The dose will be 3 to 8 millicurie (mCi) +/- 10% given intravenously at a single time prior to imaging
• Procedure Positron Emission Tomography (PET) imaging
  Participants will be scanned for approximately 30 to 45 minutes
• Drug Copper-64 labeled (64Cu-) FAP-2286
  The dose will be 3.5 to 5.5 millicurie (mCi) +/- 10% given intravenously at a single time prior to imaging

Primary outcome measures

• Count of participants with treatment-emergent adverse events [Time frame: Until end of day on the day of the injection (1 day total)]
• Proportion of radiation-absorbed doses of radiolabeled FAP-2286 (Cohorts 1a/1b only) [Time frame: Up to 3 days]
• Standardized Uptake Values (SUVs) (Cohort 2 only) [Time frame: Up to 3 days]
• Tumor-to-background (TBR) Ratio (Cohort 2 only) [Time frame: Up to 3 days]
• Proportion of positive lesions on FAP-2286 PET (Cohort 3 only) [Time frame: Up to 3 days]

Eligibility criteria

Inclusion criteria

• Age >= 18 years.
• Histopathologically confirmed solid tumors in one of the following cohorts:

a. Cohort 1 (n=11): measurable disease is not required for this cohort.

i. Agnostic to tumor type.

b. Cohort 2 (n=95): Metastatic disease present on conventional imaging defined as having RECIST 1.1 measurable disease or multiple bone metastases. Note: Presence of absence of metastatic disease for eligibility determination will be assessed by reviewing medical records. Screening imaging will not be conducted for this study.

i. Pathologically confirmed breast cancer, pancreatic adenocarcinoma, sarcoma, castrate-resistant prostate cancer, bladder cancer, colon cancer, or other cancer type.

c. Cohort 3 (n=85): No evidence of metastatic disease as defined as the absence of RECIST 1.1 measurable disease or bone metastases. Note: Presence of absence of metastatic disease for eligibility determination will be assessed by reviewing medical records. Screening imaging will not be conducted for this study.

i. Participants can be imaged at initial staging with what is judged by the treating physician to be high risk disease and where the presence of metastatic disease would greatly impact treatment planning and prognosis. Participants may also be imaged after therapy (surgery, chemotherapy or radiation therapy) if in the determination of the treating physician or investigator there is a high risk of disease recurrence that would also impact treatment plan and/or prognosis.

ii. Pathologically confirmed head and neck cancer, bladder cancer, or other cancer type.

• Ability to understand a written informed consent document, and the willingness to sign it.

Exclusion criteria

• Unlikely to comply with protocol procedures, restrictions and requirements and judged by the Investigator to be unsuitable for participation.
• Known pregnancy.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Diagnostic

Study locations

United States · 1 center

• University of California, San Francisco — San Francisco

Publications

• Kline B, Yadav S, Seo Y, Ippisch RC, Castillo J, Aggarwal RR, Kelley RK, Behr SC, Flavell RR, Lawhn-Heath C, Melisko M, Rugo HS, Wang V, Yom SS, Ha P, Jiang F, Hope TA. 68Ga-FAP-2286 PET of Solid Tumors: Biodistribution, Dosimetry, and Comparison with 18F-FDG. J Nucl Med. 2024 Jun 3;65(6):938-943. doi: 10.2967/jnumed.123.267281. PMID 38697672

Identifiers

NCT: NCT04621435 · 20929 · NCI-2020-11728

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗