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Updated: Jun 14, 2026

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A Phase I/II Study of GSK525762 Combined with Fulvestrant in Patients with Hormone Receptor-positive/HER2-negative

David W Cescon1, John Hilton2, Serafin Morales Murilo3

  • 1Princess Margaret Cancer Center, University Health Network and University of Toronto, Toronto, Ontario, Canada.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|November 22, 2023
PubMed
Abstract

Insights

This study investigated molibresib combined with fulvestrant for advanced breast cancer but found no significant clinical activity. The combination therapy did not meet efficacy endpoints, indicating limited benefit for patients with HR+/HER2- metastatic breast cancer.

Area of Science:

  • Oncology
  • Pharmacology

Background:

  • Endocrine therapy is standard for HR+/HER2- metastatic breast cancer (mBC).
  • Disease progression due to endocrine resistance is a significant challenge.
  • Molibresib, a BET inhibitor, showed potential to overcome endocrine resistance in preclinical studies.

Purpose of the Study:

  • To evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of molibresib plus fulvestrant in HR+/HER2- mBC.
  • To determine the objective response rate (ORR) of this combination therapy.

Main Methods:

  • Phase I/II dose-escalation and expansion study.
  • 123 patients with advanced/metastatic HR+/HER2- breast cancer received oral molibresib (60 or 80 mg) with intramuscular fulvestrant.
  • Patients had disease progression on prior endocrine therapy.

Main Results:

  • Common adverse events included nausea, dysgeusia, and fatigue.
  • Grade 3/4 adverse events occurred in 47-48% of patients.
  • The overall objective response rate (ORR) was 13%, below the 25% threshold for phase II progression.
  • Copy-number amplification in ctDNA was associated with poor progression-free survival.

Conclusions:

  • Molibresib in combination with fulvestrant did not demonstrate clinically meaningful activity.
  • The combination did not meet the predefined efficacy endpoint for further development.

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