Heterogeneity of 68Ga-FAPI Uptake As Imaging Biomarker in T-DXd Treatment for Brain Metastasis of HER2 Positive Breast Cancer

An Open-label Positron Emission Tomography (PET) Study to Investigate the Heterogeneity of 68Ga-FAPI Uptake Predicting the Response of T-DXd Treatment for Brain Metastasis in Patients with HER2-positive Advanced or Metastatic Breast Cancer.

The purpose of this study was to explore the predictive value of the heterogeneity of 68Ga-FAPI PET-CT uptake before treatment on the response of T-DXd treatment in patients with brain metastases of HER2-positive breast cancer. The patient underwent 68Ga-FAPI PET-CT examinations within 2 weeks before and after 2 cycles of T-DXd treatment. Heterogeneity index, SUVmax, SUVmean and other uptake values were collected to investigate the association with efficacy of T-DXd.

Study Overview

• Status: Not yet recruiting
• Conditions: Breast Cancer; Metastatic Breast Cancer
• Intervention / Treatment: Drug: Trastuzumab deruxtecan (T-DXd)

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Biyun Wang, Professor; Phone Number: 18017312387; Email: wangbiyun0107@hotmail.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Fudan University Shanghai Cancer Center
      • Contact: Biyun Wang, Professor; Phone Number: 18017312387; Email: wangbiyun0107@hotmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients aged over 18 years old.
2. ECOG 0-2.
3. Patients have been diagnosed with unresectable, locally advanced or metastatic HER2-positive breast cancer, which were by means of immunohistochemical analysis (with 3+ indicating positive status), fluorescence in situ hybridization (with an amplification ratio ≥2.0 indicating positive status), or both.
4. Brain metastasis was confirmed by MRI; measurable disease as defined by at least one intracranial cerebral metastatic lesion with diameter ≥ 1.0 cm not previously treated with radiation.
5. It is allowed to use mannitol, bevacizumab, or corticosteroids before enrollment, but dose should be stable for at least one week.
6. Plan to receive Trastuzumab deruxtecan (T-DXd).
7. Adequate bone marrow, liver, kidney and cardiac function.
8. All patients can provide an informed consent before enrolment and data collection.

Exclusion Criteria:

1. Leptomeningeal involvement.
2. Uncontrolled large amount of pleural effusion and ascites.
3. Previous treatment of T-DXd.
4. Adequate treatment washout period before enrollment, defined as: major surgery ≥4 weeks, radiation therapy ≥4 weeks, chemotherapy ≥4 weeks, small-molecule targeted agents, anticancer hormonal therapy, antibody-based treatment ≥3 weeks.
5. Patients with previous interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis require corticosteroids treatment; or any clinically active interstitial lung disease currently.
6. Use of any investigational agent within 14 d before initiation of treatment.
7. Concomitant other anticancer therapy, including cytotoxic, targeted agents, immunotherapy, antibody, retinoid or anticancer hormonal treatment.
8. History of malignancy other than squamous cell carcinoma, basal cell carcinoma of the skin or carcinoma in situ of the cervix within the last 3 years, including contralateral breast cancer.
9. Clinically significant cardiac disease.
10. Patients with known hypersensitivity to trastuzumab or 68Ga-FAPI.
11. a history of uncontrolled seizures, central nervous system disorders or psychiatric disability judged by the investigator to be clinically significant and adversely affecting compliance to study drugs.
12. Patients with the history of immunodeficiency, including HIV, or other acquired or congenital immunodeficiency diseases, or a history of organ transplantation.
13. Patients with HBsAg positive and HBV >=1000, HCV antibody positive, TP-Ab positive or HIV positive.
14. Pregnant or lactating women. Women with childbearing potential must have a negative pregnancy test at screening; also excluded are women with childbearing potential, including women whose last menstrual period was <1 year before screening, unable or unwilling to use adequate contraception from study start to 1 year after the last dose of protocol therapy. Acceptable contraception methods included the application of an intrauterine device, barrier method or total abstinence.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• 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: Trastuzumab deruxtecan (T-DXd)	Drug: Trastuzumab deruxtecan (T-DXd); Trastuzumab deruxtecan (T-DXd)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference of baseline heterogeneity index	Difference of baseline heterogeneity index evaluated by 68Ga-FAPI PET-CT between cerebral lesions reaching ORR or not with the T-DXd treatment.	6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
68Ga-FAPI PET-CT value	68Ga-FAPI PET-CT value changes (SUVmax, SUVmean ) at baseline and 2 cycles after T-DXd treatment of brain metastasis lesions.	6 weeks
Difference of baseline heterogeneity index	Difference of baseline heterogeneity index evaluated by 68Ga-FAPI PET-CT for PFS, CBR and OS in patients with brain metastasis after the T-DXd treatment.	6 weeks
Difference of baseline heterogeneity index	Difference of baseline heterogeneity index, SUVmax and SUVmean evaluated by 68Ga-FAPI PET-CT between active or stable brain metastasis.	6 weeks
68Ga-FAPI PET-CT value	68Ga-FAPI PET-CT value changes (heterogeneity index, SUVmax, SUVmean ) at baseline and 2 cycles after T-DXd treatment of whole body metastasis lesions.	6 weeks

Collaborators and Investigators

• Sponsor: Fudan University
• Investigators: Principal Investigator: Biyun Wang, Profssor, Fudan University

Study record dates

Study Major Dates

• Study Start (Estimated): February 15, 2025
• Primary Completion (Estimated): January 15, 2027
• Study Completion (Estimated): April 15, 2027

Study Registration Dates

• First Submitted: January 23, 2025
• First Submitted That Met QC Criteria: January 23, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 23, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Nervous System Neoplasms; Central Nervous System Neoplasms; Breast Neoplasms; Brain Neoplasms; Antineoplastic Agents, Immunological; Antineoplastic Agents; Immunologic Factors; Physiological Effects of Drugs; Immunoconjugates; Trastuzumab; Trastuzumab deruxtecan
• Other Study ID Numbers: YOUNGBC-33

Drug and device information, study documents

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