Granzyme B-PET: Predicting Immunotherapy Efficacy in TNBC

NCT07705438 | Recruiting

• 1 other identifier: 250-Exp134-250
• Study Type: observational
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This study plans to enroll 30 patients with locally advanced or metastatic triple-negative breast cancer (TNBC) who are scheduled to receive at least two cycles of a regimen containing an immune checkpoint inhibitor (ICI). All ICI treatments must be administered in accordance with current clinical indications. For patients who intend to participate in a clinical trial involving an ICI, they must meet the eligibility criteria of that specific trial protocol. After screening and enrollment, participants will undergo a \[68Ga\]Ga-DOTA-GSI PET/CT (Granzyme B PET/CT) scan before initiating the ICI-containing regimen and again after Cycle 2 (C2). Participants will continue the ICI regimen until disease progression, with tissue biopsies performed as needed. By integrating patients' baseline clinical characteristics, treatment outcomes, and prognostic information, this study aims to conduct a comprehensive analysis. The objective is to investigate whether the following factors, as assessed by Granzyme B PET/CT, can serve as early predictors of response to immunotherapy in patients with advanced breast cancer: baseline Granzyme B expression levels, immunotherapy-activated Granzyme B levels after C2, and the heterogeneity of Granzyme B expression at baseline and after C2.

Conditions

Triple Negative Breast Cancer; Immune Checkpoint Inhibitor; Granzyme B PET/CT

Outcome Measures

Primary Outcomes (1)

• Positive Predictive Value (PPV)

  Positive Predictive Value of Granzyme B Expression as Assessed by Granzyme B PET/CT for Objective Response.

  Up to disease progression, an average of 1 year

Interventions

[68Ga]Ga-DOTA-GSI PET/CT (Granzyme B PET/CT) OTHER

Granzyme B is a highly specific cytotoxic molecule. By binding to Granzyme B, Granzyme B-PET can visualize the distribution and activity of this enzyme within the tumor microenvironment on PET images. Performing Granzyme B-PET scans before and after immunotherapy allows for the monitoring of changes in active intratumoral immune cells during treatment. This, in turn, helps to assess whether the therapy has effectively activated the immune system and the extent of tumor cell killing. Granzyme B-PET images provide a measure of intratumoral Granzyme B uptake, thereby enabling an objective evaluation of the cytotoxic capacity of immune cells.

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Locally advanced or metastatic triple-negative breast cancer patients scheduled to receive at least two cycles of an immune checkpoint inhibitor (ICI)-containing regimen

You may qualify if:

• Age ≥ 18 years.
• Histologically confirmed unresectable locally advanced or metastatic breast cancer, with immunohistochemistry (IHC) results indicating negativity for ER, PR, and Her-2. If pathology from a metastatic lesion is available, its histology will take precedence.
• ER and PR negativity is defined as: ER \<1% positive and PR \<1% positive, OR ER \<10% with weak positivity and PR \<10% with weak positivity.
• Her-2 negativity is defined as: an IHC score of 0 or 1+; or an IHC score of 2+ with a negative FISH test result. For patients with an IHC score of 0 or 1+, a FISH test is optional but must be negative if performed.
• Decision by the clinician to treat with a regimen containing an immune checkpoint inhibitor (ICI), with the patient scheduled to receive at least 2 cycles of treatment.

You may not qualify if:

• For patients not enrolled in a clinical trial, they must have PD-L1 positive status (CPS ≥ 1), and the intended drug must be Toripalimab, as approved by the National Medical Products Administration (NMPA).
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Evidence of radiological or objective disease progression during or after the most recent systemic therapy prior to study entry, or intolerance to the toxicity of prior treatment.
• Life expectancy of ≥ 12 weeks at the time of screening.
• Presence of at least one measurable lesion that has not been previously irradiated. The lesion must have a longest diameter of ≥10 mm at baseline as measured by CT or MRI (for lymph nodes, the short axis must be ≥15 mm). In cases where only bone lesions are present, lytic or mixed lytic-blastic bone lesions that can be assessed by CT, MRI, or X-ray are acceptable.
• Left Ventricular Ejection Fraction (LVEF) ≥ 50% within 28 days prior to randomization.
• Adequate organ and bone marrow function within 14 days prior to randomization. The most recently obtained results for all parameters listed below must be used to meet the eligibility criteria:
• Hemoglobin ≥ 9 g/dL
• Absolute Neutrophil Count (ANC) ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• At baseline, Total Bilirubin (TBL) ≤ 1.5 × upper limit of normal (ULN) if no liver metastases are present, or \< 3 × ULN for patients with Gilbert's syndrome (unconjugated hyperbilirubinemia) or liver metastases.
• ALT and AST ≤ 3 × ULN, or \< 5 × ULN for patients with liver metastases.
• Serum albumin ≥ 2.5 g/dL
• Creatinine clearance ≥ 30 mL/min (calculated using the Cockcroft-Gault formula).
• International Normalized Ratio (INR) or Prothrombin Time (PT), and Partial Thromboplastin Time (PTT) or activated Partial Thromboplastin Time (aPTT) ≤ 1.5 × ULN.

Sponsors & Collaborators

• Fudan University: lead

Study Sites (1)

Fudan Cancer Hospital

Shanghai, China

RECRUITING

MeSH Terms

Conditions

Triple Negative Breast Neoplasms

Condition Hierarchy (Ancestors)

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Central Study Contacts

Juan Jin, Attending physician

CONTACT

15996290233; medjinjuan@126.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 1 Year
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Medical Oncology

Study Record Dates

• First Submitted: September 13, 2025
• First Posted: July 15, 2026
• Study Start: May 28, 2025
• Primary Completion (Estimated): May 28, 2027
• Study Completion (Estimated): May 28, 2027
• Last Updated: July 15, 2026

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)