Clinical Trial Evaluating the Biological Activity of a New Drug Identified as Prifetrastat (PF-07248144), Combined With Fulvestrant for the Treatment of Patients With Hormone Receptor Positive (HR+) and HER2 Negative (HER2-) Breast Cancer Extended to Other Organs.

NCT07340619 | Not Yet Recruiting Phase 2

• 2 other identifiers: UC-GMP-25042025-521982-29-00
• Study Type: interventional
• Target: 51
• Locations: 0 countries
• Sites: N/A

Brief Summary

Although treatments for breast cancer have improved, 20-30% of patients with early disease develop metastases (cancer that spreads to other parts of the body). Among the different types of breast cancer, hormone-sensitive cancers that do not overexpress the HER2 protein (HR+/HER2-) are the most common. For patients with this type of cancer, an endocrine treatment such as aromatase inhibitors, tamoxifen or fulvestrant, is often used and may be combined with drugs called CDK4/6 inhibitors, which help improve survival rate. However, when the cancer becomes resistant to these treatments, treatment strategies are more limited A new drug, prifetrastat (PF-07248144), which targets KAT6 proteins, which play a role in the growth of cancer cells, has shown promising results. Indeed, associated with fulvestrant, it allowed to fight against cancer in some patients who had already received many treatments. The UNLOCK-EPIBREAST study aims to investigate whether the combination of prifetrastat plus fulvestrant could offer a new therapeutic option for people with HR+/HER2- metastatic breast cancer who have already received endocrine therapy plus CDK4/6 inhibitors.

Conditions

Metastatic (Stage IV) Melanoma

Keywords

Epiddrug; breast cancer RH+ /HER2-; KAT6 inhibitor; prifetrastat; PF-07248144

Outcome Measures

Primary Outcomes (1)

• The primary objective of the study is to assess the effect of prifetrastat with fulvestrant on ctDNA-based mutation burden among patients with HR+/HER2- mBC.

  A Guardant Health (Guardant360® CDx) assay will be used for ctDNA detection and sequencing and evaluation of tumor mutation burden defined by the mean change in Variant Allele Frequency (VAF) of 74 prespecified genes, from cycle 1 to cycle 3. Primary endpoint will be evaluated per cohort (as defined in section "Therapeutic regimen" below) and in the overall population.

  From first treatment administration to disease progression or death, up to 5 years

Study Arms (2)

Cohort 1 : prifetrastat monotherapy for 15days then combination with fulvestrant

EXPERIMENTAL

Patients will receive prifetrastat 5mg QD monotherapy for 2 weeks and then combination of prifetrastat 5mg QD plus fulvestrant 500-mg intramuscular injection on day 15 cycle 1, on day 1 and day 15 of cycle 2 and then on day 15 of subsequent 28-day (±3 days) cycles. In both cohorts, men and premenopausal women will receive in addition a LH-RH analogue (goserelin, leuprorelin or triptorelin) every 28 days ±3 days, as per standard practice. Administration schedule of the analogue will follow the same schedule as described for fulvestrant, which depends on the allocated cohort.

Drug: prifetrastat monotherapy for 15 days then combination with fulvestrant

Cohort 2 : prifetrastat incombination with fulvestrant

EXPERIMENTAL

Patients will receive combination prifetrastat 5mg QD plus fulvestrant 500-mg intramuscular injection on days 1 and 15 of cycle 1 and on day 1 of subsequent 28-day (±3 days) cycles. In both cohorts, men and premenopausal women will receive in addition a LH-RH analogue (goserelin, leuprorelin or triptorelin) every 28 days ±3 days, as per standard practice. Administration schedule of the analogue will follow the same schedule as described for fulvestrant, which depends on the allocated cohort.

Drug: prifetrastat in combination with fulvestrant

Interventions

prifetrastat in combination with fulvestrant DRUG

Patients will receive combination prifetrastat 5mg QD plus fulvestrant 500-mg intramuscular injection on days 1 and 15 of cycle 1 and on day 1 of subsequent 28-day (±3 days) cycles

Cohort 2 : prifetrastat incombination with fulvestrant

prifetrastat monotherapy for 15 days then combination with fulvestrant DRUG

Patients will receive prifetrastat 5mg QD monotherapy for 2 weeks and then combination of prifetrastat 5mg QD plus fulvestrant 500-mg intramuscular injection on day 15 cycle 1, on day 1 and day 15 of cycle 2 and then on day 15 of subsequent 28-day (±3 days) cycles.

Cohort 1 : prifetrastat monotherapy for 15days then combination with fulvestrant

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: male, female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• In order to participate in the trial, all patients must meet all the following criteria:
• Patient must have signed the written informed consent prior to any study specific screening procedures.
• Note : When the patient is physically unable to give her/his written consent, a trusted person of their choice, independent from the investigator or the sponsor, can confirm in writing the patient's consent.
• Adult participants age ≥18 years.
• Histological or cytological diagnosis of advanced or metastatic ER+HER2- breast cancer.
• Participants must have progressive disease after at least 1 prior line of a CDK4/6 inhibitor and at least 1 prior line of endocrine therapy received in metastatic setting. Participants must not have received more than 3 prior lines of systemic therapies including up to 2 lines of cytotoxic chemotherapy for visceral disease in advanced or metastatic setting. Note that prior treatment with fulvestrant is permitted.
• Participants must have documentation of ER-positive tumor (≥10% positive stained cells) based on most recent tumor biopsy utilizing an assay consistent with local standards.
• Participants must have documentation of HER2-negative tumor: HER2-negative tumor is determined as immunohistochemistry score 0/1+ or HER2 2+ and negative by in situ hybridization (FISH/CISH/SISH/DISH) defined as a HER2/CEP17 ratio \<2 or for single probe assessment a HER2 copy number \<4.
• Female participants with premenopausal status (see section 5.8.4) must be willing to undergo medically induced menopause by treatment with approved LHRH agonist such as goserelin, leuprolide or equivalent agents to induce chemical menopause.
• Participants must have at least 1 measurable lesion as defined by RECIST version 1.1 that has not been previously irradiated.
• Participants must present with a metastatic site easily accessible to a biopsy procedure and be a non-bone and non-irradiated site.
• ECOG Performance Status PS 0 or 1.
• Expected survival of more than 3 months.
• Adequate bone marrow function, including:
• ANC ≥1,500/mm3 or ≥1.5 x 109/L;

You may not qualify if:

• Patients are not eligible to participate if they meet any of the following criteria:
• Participants with known symptomatic brain metastases requiring steroids. Participants with previously diagnosed brain metastases are eligible if they have completed their treatment and have recovered from the acute effects of radiation therapy or surgery prior to randomization, have discontinued corticosteroid treatment for these metastases for at least 3 weeks and are neurologically stable for 2 months (requires MRI confirmation).
• Participants with advanced/metastatic, symptomatic, visceral spread, that are at risk of life-threatening complications in the short term (including participants with massive uncontrolled effusions \[pleural, pericardial, peritoneal\], pulmonary lymphangitis, and over 50% liver involvement). Note: Participants with indwelling catheter for drainage, or requirement for drainage no more frequently than once a month will be allowed.
• Participants with any other active malignancy within 3 years prior to enrollment, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ. Other indolent cancers that do not interfere with assessment of primary cancer under study may be allowed with prior sponsor approval.
• Major surgery within 3 weeks prior to randomization.
• Radiation therapy within 3 weeks prior to randomization.
• Systemic anti-cancer therapy within 3 weeks prior to randomization. If the last immediate anti-cancer treatment contained an antibody-based agent(s) (approved or investigational), then an interval of 28 days or 5 half-lives (whichever is shorter) of the agent(s) prior to receive the study intervention treatment is required.
• Prior irradiation to \>25% of the bone marrow.
• Participants with active, uncontrolled bacterial, fungal, or viral infection, including (but not limited to) HBV, HCV, known HIV or AIDS related illness. HIV seropositive subjects who are healthy and low risk for AIDS-related outcomes could be considered eligible.
• Eligibility criteria for HIV-positive subjects should be evaluated and discussed with sponsor's medical monitor and will be based on current and past CD4 and T-cell counts, history (if any) of AIDS-defining conditions (eg, opportunistic infections), and status of HIV treatment. Also, the potential for drug-drug interactions will be taken into consideration. In equivocal cases, with positive serology, those participants with a negative viral load are potentially eligible provided the other entry criteria are met.
• Unmanageable ascites (limited medical treatment to control ascites is permitted, but all participants with ascites require review by sponsor's medical monitor).
• Baseline 12 -lead ECG that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results (eg, baseline QTc interval \>470 msec, complete LBBB, signs of an acute myocardial infarction, ST changes suggestive of active myocardial ischemia, second- or third- degree AV block, or serious bradyarrhythmias or tachyarrhythmias). If the baseline uncorrected QT interval is \>470 msec, this interval should be rate corrected using the Fridericia method and the resulting QTcF- should be used for decision making and reporting. If QTcF exceeds 470 msec, or QRS exceeds 120 msec, the ECG should be repeated 2 more times and the average of the 3 QTcF or QRS values should be used to determine the participant's eligibility. Computer -interpreted ECGs should be overread by a physician experienced in reading ECGs before excluding participants. Cases must be discussed in detail with sponsor's medical monitor to judge eligibility.
• Any of the following in the previous 6 months: myocardial infarction, long QT syndrome, Torsade de Pointes, clinically important atrial or ventricular arrhythmias (including sustained ventricular tachyarrhythmia and ventricular fibrillation), serious conduction system abnormalities (eg, bifascicular block \[defined as right bundle branch and left anterior or posterior hemiblock\], 3rd degree AV block), unstable angina, coronary/peripheral artery bypass graft, symptomatic CHF, New York Heart Association class III or IV, cerebrovascular accident, transient ischemic attack, symptomatic pulmonary embolism, and/or other clinical significant episode of thrombo embolic disease and ongoing cardiac dysrhythmias of NCI CTCAE ≥Grade 2. For Grade 2 atrial fibrillation, may be considered eligible with sponsor approval (e.g if improved to Grade 1 with non-urgent medical intervention or chronic Grade 2 atrial fibrillation with good rate control with non-urgent medical intervention). If a participant has a cardiac rhythm device/pacemaker placed and QTcF \>470 msec, the participant can be considered eligible. Participants with cardiac rhythm device/pacemaker must be discussed in detail with sponsor's medical monitor to judge eligibility.
• Therapeutic anticoagulation.
• Hypertension that cannot be controlled by optimal medical therapy (eg, ≥160/100 mmHg).

Sponsors & Collaborators

• UNICANCER: lead
• Pfizer: collaborator

MeSH Terms

Conditions

Neoplasm Metastasis; Melanoma

Interventions

Fulvestrant

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Benjamin VERRET, MD

  Gustave Roussy, Cancer Campus, Grand Paris

  PRINCIPAL INVESTIGATOR

• Fabrice ANDRE, MD

  Gustave Roussy, Cancer Campus, Grand Paris

  PRINCIPAL INVESTIGATOR

Central Study Contacts

François LEGRAND

CONTACT

0173197302; epibreast@unicancer.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 18, 2025
• First Posted: January 14, 2026
• Study Start (Estimated): May 18, 2026
• Primary Completion (Estimated): November 18, 2028
• Study Completion (Estimated): November 18, 2029
• Last Updated: January 14, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share