(The PONTIAC Study)
Research type
Research Study
Full title
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 (The PONTIAC Study) (The PONTIAC Study)
IRAS ID
1011140
Contact name
Tomás Benedit
Contact email
Sponsor organisation
Medica Scientia Innovation Research S. L.
Eudract number
2024-512360-55
Clinicaltrials.gov Identifier
Research summary
This clinical trial aims to compare the effectiveness of two treatments for advanced breast cancer: trastuzumab deruxtecan (T-DXd) and a combination of CDK4/6 inhibitors (CDK4/6i) with endocrine therapy (ET). The study will enrol patients with HR-positive, HER2-low/ultralow breast cancer who have a "non-luminal" subtype, as determined by gene expression testing. The goal is to see if T-DXd, a newer treatment, is better than the standard combination therapy in helping patients live longer without their cancer worsening (known as progression-free survival or PFS). The study will only include people with locally advanced or metastatic breast cancer that has progressed on prior hormone therapy or who have certain disease characteristics, such as oestrogen receptor expression of 50% or less, high tumour grade, or liver metastases. These patients will not have had prior systemic treatments for their advanced cancer. Participants will be randomly assigned to one of two treatment groups. One group will receive T-DXd, while the other will receive a CDK4/6i (like palbociclib, ribociclib, or abemaciclib) along with endocrine therapy (like fulvestrant or an aromatase inhibitor. This study is a phase 2, randomised, comparator trial and the average time on treatment will be approximately 11 months in the SoC and 16 months in the TDXd. Screening procedures include the collection of a recent tissue biopsy to perform a gene test. While in treatment participants will visit the clinic regularly for treatments and tests, including (a) physical examinations (b) ECGs, LVEF by ECHO or MUGA scan (c) blood tests (d) urine tests (e) CT scans (g) drug administration /IV infusion (h) eye tests and (k) questionnaires. Once the treatment is complete, all participants will complete a safety visit and enter a post-treatment follow-up period during which survival and anti-cancer therapy information will be collected until the end of the study (EoS).
REC name
South Central - Berkshire B Research Ethics Committee
REC reference
25/SC/0295
Date of REC Opinion
17 Oct 2025
REC opinion
Further Information Favourable Opinion