Pembrolizumab and Exemestane/ Leuprolide in Premenopausal HR+/ HER2- Locally Advanced or Metastatic Breast Cancer

Phase 1/2 Terminated 16 enrolled National Taiwan University Hospital Merck Sharp & Dohme LLC · collab

NaSingle-groupOpen-labelTreatment

Summary

This is an open-label, single-arm, multicenter, pilot study of pembrolizumab, exemestane, and leuprolide for subjects being resistant for front-line hormonal therapy for inoperable locally advanced or metastatic hormonal receptor positive (HR+)/ Human epidermal growth factor receptor 2 (HER2) negative breast cancer. All the patients will be included in the final tolerability and preliminary efficacy analysis. The efficacy objectives including PFS, overall response rate (ORR), clinical benefit rate (CBR), and duration of response (DOR). Adverse effects will be recorded according to CTCAE v4.0.

Timeline

Start: 2017-09-15
Primary completion: 2022-08-16
Completion: 2022-08-16

Outcome

Met primary endpoint

Stopped: “The enrolment became difficult, as most of the premenopausal women decided to receive ovarian ablation for health insurance reimbursement for CDK4/6 inhibitor for the first-line treatment, making them ineligible for joining the study.”

paper The primary endpoint of progression-free survival rate at 8 months (i.e., 64.3%) is achieved. PMID 39730000 ↗

Publications

Chen IC, Lin CH, Chang DY, Wei-Wu Chen T, Wang MY, Ma WL, Lin YT, Huang SM, Hsu CL, Lu YS. Hormone therapy enhances anti-PD1 efficacy in premenopausal estrogen receptor-positive and HER2-negative advanced breast cancer. Cell Rep Med. 2025 Jan 21;6(1):101879. doi: 10.1016/j.xcrm.2024.101879. Epub 2024 Dec 26.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Exemestane	Small molecule	25 mg	Oral
Subject	Leuprolide	Other / unclassified	3.75 mg	Subcutaneous
Subject	Pembrolizumab	Monoclonal antibody	50 mg	Intravenous
Subject	Pembrolizumab	Monoclonal antibody	100 mg	Intravenous
Subject	Pembrolizumab	Monoclonal antibody	150 mg	Intravenous