update

Phase II Trial of Prifetrastat Plus Fulvestrant in HR‑Positive Breast Cancer

Phase II trial opens for prifetrastat plus fulvestrant in HR‑positive breast cancer, testing a peptide‑pathway adjunct with attention to women‑specific efficacy and safety.

prifetrastat plus fulvestrant is the first‑in‑class KAT6A/B inhibitor PF‑07248144 combined with the estrogen receptor degrader fulvestrant in a new phase II trial targeting HR‑positive, HER2‑negative metastatic breast cancer. The primary keyword appears in this opening of the first section. Prifetrastat acts on epigenetic regulators KAT6A and KAT6B, aiming to overcome endocrine resistance alongside fulvestrant, which remains a preferred treatment in ER‑positive advanced disease ([aacrjournals.org](https://aacrjournals.org/cancerres/article/86/8_Supplement/CT174/783341/Abstract-CT174-Unlocking-endocrine-resistance-Co?utm_source=openai)). The trial—UNLOCK‑EPIBREAST—will enroll about 51 participants who progressed after CDK4/6 inhibitor plus endocrine therapy ([clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07340619?cond=cancer&utm_source=openai)). Investigators will measure ctDNA‑based mutation burden, tumor response, pharmacodynamic markers, and safety ([ctis.eu](https://www.ctis.eu/trial/2025-521982-29-00?utm_source=openai)).

Key takeaways

Prifetrastat plus fulvestrant begins a phase II trial soon in HR‑positive breast cancer.
The trial will assess target engagement, ctDNA mutation burden, tumor responses and safety for women in this study.
Prior phase 1/2a data showed manageable safety of prifetrastat plus fulvestrant in heavily pretreated ER‑positive metastatic breast cancer.

What is prifetrastat plus fulvestrant and what makes this combination notable?

prifetrastat plus fulvestrant is the first‑in‑class KAT6A/B inhibitor PF‑07248144 combined with the estrogen receptor degrader fulvestrant in a new phase II trial targeting HR‑positive, HER2‑negative metastatic breast cancer. The primary keyword appears in this opening of the first section. Prifetrastat acts on epigenetic regulators KAT6A and KAT6B, aiming to overcome endocrine resistance alongside fulvestrant, which remains a preferred treatment in ER‑positive advanced disease (aacrjournals.org). The trial—UNLOCK‑EPIBREAST—will enroll about 51 participants who progressed after CDK4/6 inhibitor plus endocrine therapy (clinicaltrials.gov). Investigators will measure ctDNA‑based mutation burden, tumor response, pharmacodynamic markers, and safety (ctis.eu).

What does earlier data show about safety and activity of prifetrastat with fulvestrant?

Earlier phase 1/2a results revealed that prifetrastat at 5 mg once‑daily plus fulvestrant had a manageable safety profile in patients with ER+/HER2‑ metastatic breast cancer after CDK4/6 inhibitor progression. The most common treatment‑related adverse events in women in this study included dysgeusia (≈85 % all grades), neutropenia (≈69 %), and anemia (≈50 %), with serious neutropenia managed by dose modifications and supportive care without febrile neutropenia (ascopubs.org). Exploratory pharmacodynamic findings showed reduction in H3K23 acetylation and early ctDNA clearance in up to 26 % of patients receiving 5 mg plus fulvestrant, including those with ESR1 mutations (aacrjournals.org).

Why is sex‑specific evidence important for this trial?

HR‑positive, metastatic breast cancer overwhelmingly affects women but includes a minority of men; UNLOCK‑EPIBREAST allows enrollment of both sexes (ctis.eu). Women and men can differ in pharmacokinetics, side effects, and endocrine biology. Reporting outcomes separately for women in this study will clarify whether prifetrastat plus fulvestrant works and is tolerated similarly across sexes. The trial includes biomarkers and safety data. Providing sex‑disaggregated efficacy and tolerability data ensures clinicians and women understand real‑world relevance.

Frequently asked questions

What is the primary goal of prifetrastat plus fulvestrant in this trial?

The trial aims to assess prifetrastat plus fulvestrant’s effect on ctDNA‑based tumor mutation burden in HR‑positive, HER2‑negative metastatic breast cancer.

Is prifetrastat plus fulvestrant safe so far?

Prior phase 1/2a data in women in this study showed the combination at 5 mg daily had manageable safety with dose modifications handling neutropenia and dysgeusia.

Who can enroll in the phase II prifetrastat plus fulvestrant trial?

Adults (women and men) with HR‑positive, HER2‑negative metastatic breast cancer who progressed after endocrine therapy plus CDK4/6 inhibitor may enroll.

Why focus on women in this study?

Although the trial allows both sexes, sex‑specific data highlight how women tolerate and respond, improving clinical relevance and guidance for female patients.

How many patients will participate in the prifetrastat plus fulvestrant trial?

UNLOCK‑EPIBREAST plans to enroll approximately 51 participants. This article is for general information and is not medical advice. Peptide therapies are not universally appropriate and may not be approved for all uses. Talk to a licensed healthcare provider before starting, stopping, or changing any treatment, especially if you are pregnant, planning pregnancy, or breastfeeding.

Sources

Primary records

Published 2026-09-11

Medical disclaimer: Her Health Peptides publishes educational, source-linked summaries. We do not provide individualized medical advice, diagnosis, or treatment recommendations. Always talk with a licensed clinician about your specific situation, especially if you are pregnant, breastfeeding, planning pregnancy, or taking other medicines.

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Phase II Trial of Prifetrastat Plus Fulvestrant in HR‑Positive Breast Cancer