Imaging of Solid Tumors Using FAP-2286

Thomas Hope

Status and phase: Enrolling; Phase 1

Conditions: Metastatic Cancer; Solid Tumors, Adult

Treatments: Procedure: Positron Emission Tomography (PET) imaging; Drug: Gallium-68 labelled (68Ga-) FAP-2286; Drug: Copper-64 labeled (64Cu-) FAP-2286

Study type: Interventional

Funder types: Other

Identifiers

NCT04621435

20929

NCI-2020-11728 (Registry Identifier)

Details and patient eligibility

About

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.

Full 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. Patients will be followed for up to 3 days after the injection of radiolabeled ligand for evaluation of adverse events.

Enrollment: 116 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Age >= 18 years

2. Histopathologically confirmed solid tumors in one of the following cohorts:

   a. Cohort 1 (n=16): measurable disease is not required for this cohort. i. Agnostic to tumor type. b. Cohort 2 (n=40): Metastatic disease present on conventional imaging defined as having RECIST 1.1 measurable disease or multiple bone metastases.

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

   ii. Pathologically confirmed cancer other than noted above (basket subgroup, n=10).

   c. Cohort 3 (n=30): No evidence of metastatic disease as defined as the absence of RECIST 1.1 measurable disease or bone metastases.

   i. Patients 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. Patients may also be imaged after definitive 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 or bladder cancer.

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

Exclusion criteria

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

Trial design

Primary purpose: Diagnostic

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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116 participants in 4 patient groups

68Ga-Dosimetry population (Cohort 1a)

Experimental group

Description:

PET imaging will begin 30 +/-10 minutes, 60 +/-15 minutes and 120 +/-20 minutes after injection of 68Ga-FAP-2286. Contrast may be administered if clinically indicated.

Treatment:

Drug: Gallium-68 labelled (68Ga-) FAP-2286

Procedure: Positron Emission Tomography (PET) imaging

64Cu-Dosimetry population (Cohort 1b)

Experimental group

Description:

PET imaging will begin 60±15 minutes, 240±30 minutes after injection,and 24±2 hours after injection of 64Cu-FAP-2286. Contrast may be administered if clinically indicated.

Treatment:

Drug: Copper-64 labeled (64Cu-) FAP-2286

Procedure: Positron Emission Tomography (PET) imaging

Participants with metastatic disease (Cohort 2)

Experimental group

Description:

Participants with metastatic disease will have PET imaging 50-100 minutes after injection of 68Ga- or 64Cu- FAP-2286. Contrast may be administered if clinically indicated.

Treatment:

Drug: Copper-64 labeled (64Cu-) FAP-2286

Drug: Gallium-68 labelled (68Ga-) FAP-2286

Procedure: Positron Emission Tomography (PET) imaging

Participants without metastatic disease (Cohort 3)

Experimental group

Description:

Participants without metastatic disease will have PET imaging 50-100 minutes after injection of 68Ga- or 64Cu- FAP-2286. Contrast may be administered if if clinically indicated.

Treatment:

Drug: Copper-64 labeled (64Cu-) FAP-2286

Drug: Gallium-68 labelled (68Ga-) FAP-2286

Procedure: Positron Emission Tomography (PET) imaging