XCancer

HER2-PET: Predicting T-DXd Efficacy and HER2 Heterogeneity

Description:

The study will be conducted as an open-label, single-center, Phase II clinical study, with a planned enrollment of 70 patients with locally advanced or metastatic HER2-positive and HER2-low breast cancer who are intended to receive at least two cycles of T-DXd monotherapy. All patients receiving T-DXd treatment must meet current clinical indications. After screening and enrollment, participants will undergo FDG-PET scans and free-of-charge HER2-PET scans prior to T-DXd treatment, with tissue biopsies performed as needed. Participants will receive single-agent T-DXd treatment until disease progression, with additional tissue biopsies performed as needed.This study will integrate and analyze patients' baseline clinical characteristics, treatment efficacy, and prognostic information, along with HER2 expression levels and HER2 expression heterogeneity as assessed by HER2-PET, to evaluate the feasibility of guiding T-DXd treatment in patients with advanced breast cancer.

Sponsor:

Fudan University

Contacts:

Juan Jin Attending physician (CONTACT)

medjinjuan@126.com

15996290233

Government Study Link:

NCT07586215 - Click here to see study on

ClinicalTrials.gov

FDG

Isotope(s):
Target(s):
  • Glucose Transport
Ligand Class: Small Molecules
Inclusion
  • Absolute Neutrophil Count (ANC) ≥ 1500/mm3;
  • Platelet count ≥ 100,000/mm3;
  • 1 For HER2-positive breast cancer, patients must have received at least one prior anti-HER2 targeted therapy.
  • Serum albumin ≥ 2.5 g/dL;
  • At least one measurable lesion that has not been previously irradiated, with a longest diameter ≥ 10 mm as accurately measured by CT or MRI at baseline (except for lymph nodes, which must have a short axis ≥ 15 mm). Alternatively, if only bone lesions are present, evaluable osteolytic or mixed osteolytic/blastic bone lesions as assessed by CT, MRI, or X-ray are acceptable.
  • Total bilirubin (TBL) ≤ 1.5 × Upper Limit of Normal (ULN) at baseline in the absence of liver metastases; or \< 3 × ULN in the presence of Gilbert's syndrome (unconjugated hyperbilirubinemia) or liver metastases;
  • ALT and AST ≤ 3 × ULN; or \< 5 × ULN for patients with liver metastases;
  • 2 For HER2-low breast cancer, patients must have received at least one prior line of systemic therapy for metastatic disease, or have relapsed within 6 months during or after completion of adjuvant chemotherapy.
  • Creatinine clearance ≥ 30 mL/min (calculated using the Cockcroft-Gault formula);
  • Histologically confirmed unresectable locally advanced or metastatic breast cancer, with immunohistochemistry (IHC) results indicating HER2-positive (IHC 3+; or IHC 2+ and FISH-positive) or HER2-low expression (IHC 1+; or IHC 2+ and FISH-negative).
  • Prior treatment meeting one of the following criteria:
  • Hemoglobin ≥ 9 g/dL;
Exclusion
  • Clinically significant pulmonary-specific comorbidities, including but not limited to any underlying pulmonary disease (e.g., pulmonary embolism within three months prior to randomization, severe asthma, severe chronic obstructive pulmonary disease \[COPD\], restrictive lung disease, significant pleural effusion, etc.) and any autoimmune, connective tissue, or inflammatory disease with associated pulmonary involvement (e.g., rheumatoid arthritis, Sjögren's syndrome, sarcoidosis, etc.), and/or prior lung resection.
  • History of (non-infectious) interstitial lung disease (ILD)/pneumonitis requiring steroid treatment, current ILD/pneumonitis, or suspected ILD/pneumonitis that cannot be ruled out by imaging at screening.
  • Patients who have used immunosuppressive agents within 14 days prior to the first dose of study drug, with the exception of those using intranasal and inhaled corticosteroids, or systemic corticosteroids at a dose less than 10 mg/day prednisone or an equivalent dose.