A Randomized Phase II Study to Evaluate the Safety and Efficacy of Trastuzumab Deruxtecan Versus CDK4/6 Inhibitor-based Endocrine Therapy as First-line Therapy of HR-positive and HER2-low/Ultralow Advanced Breast Cancer Patients Classified as Non-luminal Subtype According to Gene Expression Profiling. (PONTIAC)

NCT06486883 Phase 2 RECRUITING

This trial studies a type of advanced breast cancer defined as hormone receptor HR-positive/HER2-negative and classified as non-luminal by gene expression profiling (PAM50). Patients will be treated with trastuzumab deruxtecan (T-DXd) or with physician's choice of CDK4/6 inhibitor (CDK4/6i) plus endocrine therapy (ET). The main purpose of the study is to analyze the efficacy of T-DXd in patients who have HR-positive and HER2-low/ultralow advanced breast cancer classified as non-luminal subtype.

Details

Lead sponsor	MedSIR
Phase	Phase 2
Status	RECRUITING
Enrolment	200
Start date	2025-06-30
Completion	2028-01

Conditions

• Advanced Breast Cancer
• Advanced Breast Carcinoma
• Hormone Receptor Positive Breast Carcinoma

Interventions

• Trastuzumab deruxtecan (T-DXd, DS-8201a)
• CDK4/6i plus ET

Primary outcomes

• Progression-free survival (PFS) — Up to 25 months
  PFS, defined as the period from randomization date to the first occurrence of documented radiographic disease progression or death from any cause, whichever occurs first, as determined locally by the investigator using RECIST v.1.1. in HER2-low patients.
• Progression-free survival (PFS) — Up to 25 months
  PFS, defined as the period from randomization date to the first occurrence of documented radiographic disease progression or death from any cause, whichever occurs first, as determined locally by the investigator using RECIST v.1.1 in all patients.

Countries

Belgium, France, Germany, Italy, Poland, Portugal, Spain