Study of [68Ga]FAPI-46 PET in Patients With Pancreatic Ductal Carcinoma (FAPI-46 PDAC)

A Phase 2, Multicenter, Single Arm, Open Label Non-Randomized Study of [68Ga]FAPI-46 PET in Patients With Resectable or Borderline Resectable Pancreatic Ductal Carcinoma

This is a prospective, multi-center, single arm, open label, non-randomized study to evaluate the ability of [68Ga]FAPI-46 to detect FAP expressing cells in patients with resectable or borderline resectable PDAC. The [68Ga]FAPI-46 PET scans will be acquired after initial staging using institutional standard methods. If the participant is prescribed neoadjuvant therapy, a second [68Ga]FAPI-46 PET scan will be performed within 21 days prior to planned surgical resection. This will be followed by histopathology and IHC analyses and comparison to resected PDAC tumor specimens.

Study Overview

• Status: Completed
• Conditions: FAP; PDAC - Pancreatic Ductal Adenocarcinoma
• Intervention / Treatment: Drug: [68Ga]FAPI-46

• Study Type: Interventional
• Enrollment (Actual): 63
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095
      • University of California Los Angeles (UCLA) Health
  • Michigan
    • Grand Rapids, Michigan, United States, 49503
      • BAMF Health
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • New York
    • New York, New York, United States, 10016
      • NYU Langone Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Pathologically confirmed pancreatic ductal adenocarcinoma
2. Treatment-naïve
3. Staged as resectable or borderline-resectable
4. Planned to undergo surgical resection or to receive neoadjuvant therapy (i.e., chemotherapy, radiation therapy, or combination) and subsequent possible surgical resection
5. Anatomic imaging (e.g., CT, MRI) obtained within ≤ 28 days of consent
6. Age ≥ 18 years
7. Completed informed consent as determined per the IRB of record

Exclusion Criteria:

1. Pregnant as determined by a pregnancy test as per institutional guidelines for individuals of child-bearing potential
2. Declining to use effective contraceptive methods during the study (for individuals of child-producing potential)
3. Need for emergent surgery that would be delayed by participation
4. Bacterial, viral, or fungal infections requiring systemic therapy
5. Serious co-morbidities and serious nonmalignant disease (e.g., hydronephrosis, kidney failure, liver failure, systemic or local inflammatory or autoimmune diseases or other conditions) that in the opinion of the investigator, physician of record and/or Sofie could compromise patient safety and/or protocol objectives.
6. Known diagnosis of autoimmune disorders
7. Patients receiving any other investigational agent within the past 28 days
8. Breastfeeding. Note: nursing parents are allowed if the potential participant commits to pumping breast milk and discarding it from injection to ≥ 24 hours from the time of the [68Ga]FAPI-46 injection.
9. Known hypersensitivity to any excipients used in [68Ga]FAPI-46:

trace amounts of sodium acetate sodium ascorbate and/or hydrochloric acid

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 68Ga-FAPI-46 PET/CT; Patients receive [68Ga]FAPI-46 intravenously followed by PET/CT 15-25 minutes later	Drug: [68Ga]FAPI-46; [68Ga]-FAPI-46 is a radioactive diagnostic agent indicated for use with Positron Emission Tomography (PET) imaging for the detection of Fibroblast Activation Protein (FAP) positive cancer cells and cancer-associated fibroblasts (CAF) in patients with pancreatic ductal adenocarcinoma (PDAC).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sensitivity of [68Ga]FAPI-46 PET Imaging to Detect PDAC, Using Histopathology as Truth Standard	Sensitivity was defined as the proportion of participants with histopathology-confirmed PDAC who had a positive [⁶⁸Ga]FAPI-46 PET result for the primary lesion. Sensitivity was calculated by comparing positive and negative [⁶⁸Ga]FAPI-46 PET findings with the corresponding histopathology results, using a single readable PET image matched to its reference histopathology assessment. Sensitivity was calculated as A / (A + C), where A represents true-positive findings and C represents false-negative findings. Higher sensitivity indicates a greater ability of [⁶⁸Ga]FAPI-46 PET to detect FAP-expressing disease and a lower likelihood of false-negative results, thereby reflecting the effectiveness of the imaging modality relative to the histopathological reference standard.	Day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation Between [⁶⁸Ga]FAPI-46 PET Uptake (SUVmax) and IHC Staining Intensity (H-score) in FAP-positive Lesions	The association between [⁶⁸Ga]FAPI-46 PET uptake, measured by maximum standardized uptake value (SUVmax), and FAP expression, assessed by H-score from histopathology, was evaluated. The relationship between SUVmax and H-score was assessed using the Spearman rank correlation coefficient, with corresponding 95% confidence intervals, in participants with evaluable PET imaging and histopathology results may not be linear owing in part to the H score ceiling of 300. All available paired PET and H-score measurements were included; when both pre- and post-neoadjuvant therapy data were available, each time point was analyzed separately. Spearman's rho was selected because it assesses monotonic relationships between ordinal or continuous variables and does not assume linearity, which may not be appropriate for the relationship between SUVmax and H-score.	Day 1
Sensitivity of [68Ga]FAPI-46 PET to Detect FAP-expressing Cells Using H-score as Standard of Truth	Sensitivity was defined as the proportion of participants with IHC confirmed FAP-expressing cells who had a positive [68Ga]FAPI-46 PET result for the primary lesion. Sensitivity was calculated as A / (A + C), where A represents true positive findings and C represents false negative findings. Higher sensitivity indicates a greater ability of [68Ga]FAPI-46 PET to detect IHC confirmed FAP expression and a lower likelihood of false negative results, thereby reflecting the effectiveness of the imaging modality relative to the IHC reference standard. Sensitivity was presented considering IHC-positive results using 3 IHC cut-off values: > 50: Overall positive versus negative expression; > 100: Moderate to high expression and > 200: High expression only.	Day 1
Specificity of [68Ga]FAPI-46 PET to Detect FAP-expressing Cells Using H-score as Standard of Truth	Specificity was defined as the proportion of participants without IHC-confirmed FAP-expressing cells who had a negative [68Ga]FAPI-46 PET result for the primary lesion. Specificity was calculated by comparing positive and negative [68Ga]FAPI-46 PET findings with the corresponding IHC results, using a single readable PET image matched to its reference IHC assessment. Specificity was calculated as D / (B + D), where B represents false-positive findings and D represents true-negative findings. PET results were compared with the corresponding IHC reference assessment using a single readable PET image per participant. Specificity was evaluated considering IHC-positive results using 3 IHC cut-off values > 50: Overall positive versus negative expression; > 100: Moderate to high expression and > 200: High expression only.	Day 1
Number of Participants Reporting Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs	An AE is any untoward medical occurrence in a clinical study participant whether or not considered related to the study intervention. A TEAE is any AE that occurs after receipt of one or more doses of study drug through the end of study for that participant. A SAE is defined as any untoward medical occurrence that, at any dose: results in death or is life-threatening or requires inpatient hospitalization or prolongation of existing hospitalization or results in persistent disability/incapacity or is a congenital anomaly/birth defect or is a medically significant / important event or reaction.	Up to 2 years

Collaborators and Investigators

• Sponsor: SOFIE

Publications and helpful links

General Publications

• Karbhari A, Mosessian S, Trivedi KH, Valla F Jr, Jacobson M, Truty MJ, Patnam NG, Simeone DM, Zan E, Brennan T, Chen H, Kuo PH, Herrmann K, Goenka AH. Gallium-68-labeled fibroblast activation protein inhibitor-46 PET in patients with resectable or borderline resectable pancreatic ductal adenocarcinoma: A phase 2, multicenter, single arm, open label non-randomized study protocol. PLoS One. 2023 Nov 27;18(11):e0294564. doi: 10.1371/journal.pone.0294564. eCollection 2023.

Study record dates

Study Major Dates

• Study Start (Actual): May 2, 2022
• Primary Completion (Actual): March 7, 2025
• Study Completion (Actual): November 4, 2025

Study Registration Dates

• First Submitted: February 10, 2022
• First Submitted That Met QC Criteria: February 21, 2022
• First Posted (Actual): March 2, 2022

Study Record Updates

• Last Update Posted (Actual): May 29, 2026
• Last Update Submitted That Met QC Criteria: May 28, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: PDAC; Fibroblast Activation Protein Inhibitor (FAPI)
• Additional Relevant MeSH Terms: Endocrine System Diseases; Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Digestive System Neoplasms; Digestive System Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Carcinoma; Neoplasms, Ductal, Lobular, and Medullary; Pancreatic Neoplasms; Carcinoma, Ductal; Carcinoma, Pancreatic Ductal; Molecular Mechanisms of Pharmacological Action; Radiopharmaceuticals; FAPI-46
• Other Study ID Numbers: GaFAPI-2022P2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No