AzTrials
AzTrials

Advanced Breast CancerPhase 2PONTIACNCT06486883

Safety and Efficacy of T-DXd vs. CDK4/6i-based ET as First-line Therapy of HR-positive and HER2-low/Ultralow Advanced Breast Cancer Patients Classified as Non-luminal Subtype

A Phase 2 study testing Trastuzumab deruxtecan (T-DXd, DS-8201a) and CDK4/6i plus ET in people with Advanced Breast Cancer and Advanced Breast Carcinoma, run by MedSIR at 79 sites in 10 countries.

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Sites and contacts
Official record
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Trial summary

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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Trastuzumab deruxtecan (T-DXd, DS-8201a) and CDK4/6i plus ET
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
200 participants
Where
79 sitesin 10 countries
Study dates
30 Jun 2025to Jan 2028
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients must be capable to understand the purpose of the study and have signed written informed consent form (ICF) prior to beginning specific protocol procedures.
  • Female or male patients ≥ 18 years of age at the time of signing ICF.
  • ECOG performance status of 0-1.
  • Minimum life expectancy of ≥ 12 weeks at screening.
  • Evidence of HER2-low expression (1+ by immunohistochemistry (IHC) or 2+ and negative by an in situ hybridization [ISH] test) or HER2-ultralow (IHC 0 with faint membrane staining and in ≤ 10% of tumor cells) breast cancer according to the most recent American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines determined by a MEDSIR's designated central laboratory, using Ventana 4B5 antibody. This assessment has to be done on the most recently available (archived or newly collected) formalin-fixed, paraffin-embedded (FFPE) tumor tissue blocks (≤ 6 weeks or FFPE of a tumor sample obtained after last prior systemic therapy) from core or excisional biopsy from a locally recurrent (breast or locoregional lymph nodes) or metastatic tumor lesion, excluding bone metastases.
  • Non-luminal breast cancer subtype as per central PAM50 analysis determined in the most recently available (archived or newly collected) FFPE tumor tissue blocks (≤ 6 weeks or FFPE of a tumor sample obtained after last prior systemic therapy) from core or excisional biopsy from a locally recurrent (breast or locoregional lymph nodes) or metastatic tumor lesion with the exception of bone metastases.
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  • Patients must have HR-positive (estrogen receptor [ER] and/or progesterone receptor [PgR]-positive defined as ≥ 1% positive stained cells) status according to the most recent ASCO/CAP guidelines locally determined prior to study entry.
  • Unresectable locally recurrent or metastatic breast cancer documented by computerized tomography (CT) scan or magnetic resonance imaging (MRI) that is not amenable to resection with curative intent.
  • Evaluable disease according to RECIST v.1.1. Patients with bone-only disease are not allowed. Patients with bone metastases with soft tissue masses measuring > 10 mm are eligible.
  • Patients must have endocrine resistance criteria:
  • disease progression during adjuvant ET or within the first year of completing adjuvant ET;
  • or endocrine sensitivity criteria:
  • de novo metastatic disease or disease progression ≥ 12 months after completing adjuvant ET with at least one of the following requirements:
  • Estrogen receptor ≤ 50% positive stained cells;
  • and/or high histological grade or Ki67 > 50% on primary tumor;
  • and/or liver metastases;
  • and/or known non-luminal subtype as per local PAM50 analysis.
  • No prior treatment with any systemic therapy for advanced disease.
  • Patients treated with a CDK4/6i in the adjuvant setting with a treatment-free interval (TFI) ≥ 12 months following CDK4/6i treatment completion are eligible.
  • Patients have adequate bone marrow, liver, and renal function:
  • Hematological (without platelet, red blood cell transfusion, and/or granulocyte colony-stimulating factor support within 14 days before first study treatment dose): White blood cell (WBC) count > 3.0 x 109/L, absolute neutrophil count (ANC) ≥ 1.5 x 109/L, platelet count ≥ 100.0 x 109/L, and hemoglobin ≥ 9.0 g/dL (≥ 5.6mmol/L).
  • Hepatic: Serum albumin ≥ 2.5 g/dL; total bilirubin ≤ 1.5 times upper limit of normal (x ULN) (≤ 3 x ULN in patients with liver metastases or know history of Gilbert's disease); alkaline phosphatase (ALP) ≤ 2.5 x ULN (≤ 5 x ULN in patients with liver/or bone metastases); aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3 x ULN (≤ 5 x ULN in patients with liver metastases).
  • Renal: Creatinine clearance ≥ 30 mL/min as determined by Cockcroft Gault (using actual body weight).
  • Coagulation: International normalized ratio or prothrombin time and either partial thromboplastin or activated partial thromboplastin time ≤ 1.5 × ULN.
  • Resolution of all acute toxic effects of prior anti-cancer therapy to Grade ≤ 1 as determined by the US National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 (v.5.0) (except for alopecia or other toxicities not considered a safety risk for the patient at investigator's discretion).
  • Women of childbearing potential who are sexually active with a non-sterilized male partner must have a negative serum pregnancy test within 14 days before study treatment initiation. In addition, they must agree to use one highly effective method of birth control from the time of screening until 7 months after the last dose of T-DXd, or within the time period specified per local prescribing guidelines after the final dose of physician's choice of CDK4/6i plus ET. Female patients must refrain from egg cell donation and breastfeeding during this same period.
  • Male participants who are sexually active with a female partner of childbearing potential must be surgically sterile or using an acceptable method of contraception from the time of screening until 4 months after the last dose of T-DXd, or within the time period specified per local prescribing guidelines after the final dose of physician's choice of CDK4/6i plus ET. Male participants must not donate or bank sperm during this same period.
  • Patients must be accessible for treatment and follow-up.

Who cannot join

  • Current participation in another therapeutic clinical trial, except other translational studies.
  • Treatment with approved or investigational cancer therapy within 3 weeks prior to initiation of study drug.
  • Treatment with chloroquine/hydroxychloroquine within 14 days prior to initiation of study drug.
  • Have previously been treated with T-DXd and/or fulvestrant. Note: patients who experienced relapse after more than 1 year from completion of fulvestrant are eligible.
  • Note I: previous treatment with anti-HER2 therapies in (neo-) adjuvant setting will be allowed for participants who showed conversion from HER2-positive expression in primary breast tumor sample to HER2-low or HER2-ultralow expression (HER2 loss) in relapsed tumor sample.
  • Patients with advanced, symptomatic, visceral spread, that are at risk of life-threatening complications in the short term (including patients with massive uncontrolled effusions [pleural, pericardial, and/or peritoneal] and pulmonary lymphangitis).
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  • Impairment of gastro-intestinal (GI) function or GI disease that may significantly alter the absorption of CDK4/6i, such as history of GI surgery which may result in intestinal blind loops and patients with clinically significant gastroparesis, short bowel syndrome, unresolved nausea, vomiting, active inflammatory bowel disease, or diarrhea of CTCAE Grade > 1.
  • Known central nervous system (CNS) involvement (brain metastases and/or leptomeningeal carcinomatosis). Subjects with clinically inactive brain metastases may be included in the study. Subjects with treated brain metastases that are no longer symptomatic and who require no treatment with corticosteroids or anticonvulsants may be included in the study if they have recovered from the acute toxic effect of radiotherapy.
  • Have a concurrent malignancy or malignancy within 5 years of study enrollment with the exception of carcinoma in situ of the cervix and basal cell carcinoma or squamous cell carcinoma of the skin that has been previously treated with curative intent. For other cancers considered to have a low risk of recurrence, discussion with the Sponsor's Medical Monitor is required.
  • Known allergy or hypersensitivity reaction to any of the investigational medicinal products (IMPs) or their inactive ingredients.
  • Palliative radiotherapy with a limited field of radiation within 2 weeks or with wide field of radiation or to more than 30% of the bone marrow within 4 weeks prior to start of study treatment.
  • Major surgical procedure or significant traumatic injury within 4 weeks before the first dose of study treatment or anticipation of need for major surgery within the course of the study treatment.
  • Has an active cardiac disease or a history of cardiac dysfunction or conduction abnormalities including, but not confined, to any of the following:
  • Participants with a medical history of myocardial infarction within 6 months before screening, symptomatic congestive heart failure (NYHA Class II to IV), unstable angina pectoris, or a recent (< 6 months) cardiovascular event including stroke. Participants with troponin levels above ULN at screening (as defined by the manufacturer), and without any myocardial related symptoms, should have a cardiologic consultation to rule out myocardial infarction.
  • Left ventricular ejection fraction (LVEF) < 55% as determined by multigated acquisition (MUGA) scan or echocardiogram (ECHO).
  • History of arrhythmia (multifocal premature ventricular contractions, bigeminy, trigeminy, or ventricular tachycardia), which is symptomatic or requires treatment (NCI-CTCAE Grade 3), symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia. Participants with atrial fibrillation controlled by medication or arrhythmias controlled by pacemakers will be permitted to enroll.
  • QT interval corrected by Fridericia's formula (QTcF) prolongation to > 470 ms (females) or > 450 ms (males) based on average of the screening triplicate 12-lead electrocardiogram (ECG).
  • History of QT prolongation associated with other medications that required discontinuation of that medication, or any current concomitant medication known to prolong the QT interval and cause Torsades de Pointes.
  • Congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death under 40 years of age in first-degree relatives.
  • Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder (e.g., pulmonary emboli within 3 months of the study enrolment, severe asthma, severe chronic obstructive pulmonary disease, restrictive lung disease, pleural effusion, post COVID-19 pulmonary fibrosis, etc.), and any autoimmune, connective tissue, or inflammatory disorders with pulmonary involvement (e.g., rheumatoid arthritis, Sjogren's syndrome, sarcoidosis, etc.), or prior pneumonectomy (complete).
  • Has a history of non-infectious interstitial lung disease (ILD)/pneumonitis that required steroids, has current ILD/pneumonitis, or has suspected ILD/pneumonitis that cannot be ruled out by imaging at screening.
  • Pregnant or lactating women or patients not willing to apply highly effective contraception as defined in the protocol.
  • Current known infection with hepatitis B virus (HBV), or hepatitis C virus (HCV). Patients with past HBV infection or resolved HBV infection (defined as having a negative hepatitis B surface antigen [HBsAg] test and a positive hepatitis B core antibody [HBcAb] test, accompanied by a negative HBV DNA test), and > 6 months off anti-viral treatment are eligible. Those participants should be closely monitored for HBV reactivation and have access to a local hepatitis B expert during and after the study.
  • Patients positive for HCV antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA.
  • Patients with HCV co-infection or history of HCV co-infection.
  • Patients with cirrhosis or fibrosis on prior imaging or biopsy.
  • Has an active primary immunodeficiency or known human immunodeficiency virus (HIV) infection.
  • Other active uncontrolled infection at the time of enrollment.
  • Receipt of live or attenuated vaccine within 30 days prior to the first dose of study treatment.
  • A history of uncontrolled seizures, CNS disorders, or serious and/or unstable pre-existing psychiatric disability judged by the investigator to be clinically significant and adversely affecting compliance to study drugs or interfering with subject safety.
  • Current use of food or drugs known to be potent CYP3A4 inhibitors, drugs known to be potent CYP3A4 inducers (for examples, see the Prohibited Medications Section).
  • Known substance abuse or any other concurrent severe and/or uncontrolled medical condition that would, in the investigator's judgment, contraindicate patient participation.
  • Inability or unwillingness to comply with the requirements of the protocol in the opinion of the investigator.

Trial locations and contacts

79 sites in 10 countries. Contact the study team or a site near you to ask about taking part.

MEDSIR contact

+ 34 932 214 135

contact.trials@medsir.org

79 sites in 10 countries

Spain31 sites, 31 recruiting

  • Complejo Hospitalario Universitario A Coruña (CHUAC)

    A Coruña, 15006

    Recruiting

  • Centro Oncológico de Galicia

    A Coruña, 15009

    Recruiting

  • Hospital Universitario San Juan de Alicante

    Alicante, 03550

    Recruiting

  • Institut Català d' Oncologia Badalona (ICO)

    Badalona, 08916

    Recruiting

  • Hospital Quirónsalud Sagrado Corazón

    Barcelona, Barcelona, 41013

    Recruiting

  • UOMI Cancer Center

    Barcelona, 08017

    Recruiting

  • Hospital Universitari Dexeus

    Barcelona, 08028

    Recruiting

  • Hospital Clínic i Provincial de Barcelona

    Barcelona, 08036

    Recruiting

  • Hospital Universitario de Basurto

    Bilbao, 48013

    Recruiting

  • Hospital San Pedro de Alcántara

    Cáceres, Cáceres, 1003

    Recruiting

  • Institut Català d' Oncologia Girona (ICO)

    Girona, Girona, 17007

    Recruiting

  • Hospital Universitario Clínico San Cecilio

    Granada, Granada, 18007

    Recruiting

  • Complejo Hospitalario de Jaén

    Jaén, Jaén, 23007

    Recruiting

  • Hospital Universitario Arnau de Vilanova de Lleida

    Lleida, 25198

    Recruiting

  • Hospital Universitario Ramón y Cajal

    Madrid, Madrid, 28034

    Recruiting

  • Hospital Beata María Ana

    Madrid, 28007

    Recruiting

  • Hospital Clínico San Carlos

    Madrid, 28040

    Recruiting

  • Hospital Universitario Doce de Octubre

    Madrid, 28041

    Recruiting

  • Hospital Gregorio Marañón

    Madrid

    Recruiting

  • Hospital Universitario Puerta de Hierro Majadahonda

    Majadahonda, Madrid, 28222

    Recruiting

  • Hospital Universitario Virgen de la Victoria

    Málaga, 29010

    Recruiting

  • Hospital Clínico Universitario Virgen de la Arrixaca

    Murcia, Murcia, 30120

    Recruiting

  • Hospital Universitari Sant Joan de Reus

    Reus, Tarragona, 43204

    Recruiting

  • Complejo Hospitalario Universitario de Santiago (CHUS)

    Santiago de Compostela, 15706

    Recruiting

  • Hospital Universitario Virgen Macarena

    Seville, 41009

    Recruiting

  • Hospital Clínico Universitario de Valencia

    Valencia, Valencia, 46010

    Recruiting

  • Instituto Valenciano de Oncología (IVO)

    Valencia, 46009

    Recruiting

  • Hospital Universitari i Politècnic La Fe

    Valencia, 46026

    Recruiting

  • Hospital Arnau de Vilanova de Valencia

    Valencia

    Recruiting

  • Hospital Clínico Universitario Lozano Blesa

    Zaragoza, 50009

    Recruiting

  • Hospital QuirónSalud Zaragoza

    Zaragoza, 50012

    Recruiting

Other trials in Spain

Italy15 sites, 15 recruiting

  • A.O.U. Ospedali Riuniti di Ancona

    Ancona, 60126

    Recruiting

  • Centro di Riferimento Oncologico di Aviano

    Aviano, 33081

    Recruiting

  • AOU Careggi

    Florence, 50134

    Recruiting

  • Ospedale Policlinico San Martino

    Genova, 16132

    Recruiting

  • Instituto Europeo di Oncologia

    Milan, 20141

    Recruiting

  • AOU policlinico di Modena

    Modena

    Recruiting

  • Ospedale San Gerardo

    Monza, 20900

    Recruiting

  • Federico II Napoli

    Naples, 80131

    Recruiting

  • Istituto Nazionale Tumori Irccs "Fondazione G Pascale"

    Naples, 80131

    Recruiting

  • Ospedale Sacro Cuore Don Calabria Negrar

    Negrar

    Recruiting

  • Azienda Ospedaliero- Universitaria Maggiore Della Carita

    Novara, 28100

    Recruiting

  • Istituto Oncologico Veneto

    Padova

    Recruiting

  • Oncologia medica AUSL Piacenza

    Piacenza, 29100

    Recruiting

  • Ospedale di Macerata

    Province of Macerata, 62100

    Recruiting

  • Fondazione Policlinico Universitario Agostino Gemelli

    Roma, 00168

    Recruiting

Other trials in Italy

Portugal10 sites, 10 recruiting

  • Hospital de Cascais

    Alcabideche, 2755-009

    Recruiting

  • Unidade Local de Saúde Amadora/Sintra - Hospital Fernando da Fonseca

    Amadora, 2720-276

    Recruiting

  • Unidade Local de Saúde da Região de Aveiro

    Aveiro

    Recruiting

  • Unidade Local de Saúde do Alto Ave

    Braga

    Recruiting

  • Unidade Local de Saúde de Santa Maria

    Lisbon, 1649-035

    Recruiting

  • Hospital Da Luz Lisboa

    Lisbon

    Recruiting

  • Unidade Local de Saúde de Trás-os-Montes e Alto Douro

    Lordelo, Vila Real District, 5000-508

    Recruiting

  • Hospital Beatriz Ângelo

    Loures

    Recruiting

  • Instituto Portugues Oncologia de Porto (IPO)

    Porto

    Recruiting

  • Unidade Local de Saúde de Santo António

    Porto

    Recruiting

Other trials in Portugal

France5 sites, 5 recruiting

  • Centre Francois Baclesse

    Caen

    Recruiting

  • CHU Lyon Sud

    Lyon

    Recruiting

  • Institute Paoli Calmettes

    Marseille

    Recruiting

  • Institut Curie

    Paris

    Recruiting

  • CHU Saint Etienne

    Saint-Priest-en-Jarez, 42055

    Recruiting

Other trials in France

Germany5 sites, 5 recruiting

  • MVZ Klinikum Aschaffenburg

    Aschaffenburg

    Recruiting

  • Hämatologie-Onkologie im Zentrum MVZ

    Augsburg

    Recruiting

  • Universitätsklinikum Carl Gustav Carus Dresden

    Dresden

    Recruiting

  • Kliniken Essen Mitte

    Essen

    Recruiting

  • Klinikum Worms - Frauenklinik

    Worms, 67550

    Recruiting

Other trials in Germany

Belgium4 sites, 4 recruiting

  • Algemeen Ziekenhuis Klina

    Brasschaat

    Recruiting

  • Ghent University Hospital

    Ghent

    Recruiting

  • CHU Helora - Hopital de Mons

    Mons

    Recruiting

  • Cliniques universitaires Saint-Luc

    Woluwe-Saint-Lambert

    Recruiting

Other trials in Belgium

Austria3 sites, 3 recruiting

  • Medizinische Universität Graz

    Graz

    Recruiting

  • Kepler Universitäts Klinikum

    Linz

    Recruiting

  • Medical University of Vienna

    Vienna

    Recruiting

Other trials in Austria

United Kingdom3 sites, 3 recruiting

  • Royal United Hospitals Bath NHS Foundation Trust

    Bath

    Recruiting

  • The Christie NHS Foundation Trust

    Lancaster

    Recruiting

  • Barts Health NHS Trust

    London

    Recruiting

Other trials in United Kingdom

Poland2 sites, 2 recruiting

  • Medtrials Sp. z o.o.

    Krakow

    Recruiting

  • Wojskowy Instytut Medyczny

    Legionowo

    Recruiting

Other trials in Poland

Netherlands1 site, 1 recruiting

  • Netherlands Cancer Institute

    Amsterdam

    Recruiting

Other trials in Netherlands

About this study

Official 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.

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.

Read the detailed description

This is an international, multicenter, two-arm, randomized, phase II clinical trial for patients with unresectable locally recurrent or metastatic HR-positive and HER2-low/ultralow breast cancer classified as non-luminal by gene expression profiling. Female or male patients ≥ 18 years of age with HR-positive and HER2-low/ultralow locally recurrent inoperable or metastatic breast cancer classified as non-luminal subtype by central PAM50 analysis will be enrolled. Patients will be randomized to T-DXd 5.4 mg/kg body weight administered as an IV infusion on Day 1 of each 21-day cycle or physician's choice of CDK4/6 inhibitor plus endocrine therapy. The main objective of the study is to demonstrate that first-line T-DXd compared with CDK4/6i plus ET is superior in prolonging the progression free survival (PFS) based on investigator assessment in patients with HR-positive, HER2-low advanced breast cancer classified as non-luminal by central PAM50 analysis (HER2-low population) and all patients.

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

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Trastuzumab deruxtecan (T-DXd, DS-8201a)Drug

    Patients will receive T-DXd 5.4 mg/kg body weight administered as an intravenous (IV) infusion on Day 1 (D1) of each 21-day cycle. The initial dose will be administered as a 90-minute IV infusion.

  • CDK4/6i plus ETDrug

    Patients will receive physician's choice of CDK4/6 inhibitor (CDK4/6i) including palbociclib, ribociclib, and abemaciclib; physician's choice of endocrine therapy (ET) including fulvestrant, letrozole, anastrozole, and exemestane.

Study groups in NCT06486883
Study groupRoleWhat they receive
Arm AExperimentalNot described
Receives: Drug: Trastuzumab deruxtecan (T-DXd, DS-8201a)
Arm BActive comparatorNot described
Receives: Drug: CDK4/6i plus ET

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression-free survival (PFS)

    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.

    Measured: Up to 25 months

  2. Progression-free survival (PFS)

    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.

    Measured: Up to 25 months

Secondary outcomes (14)

  1. Overall survival (OS)

    OS, defined as the period from randomization date to death from any cause, as determined locally by the investigator (in all patients and HER2-low population).

    Measured: Up to 25 months

  2. Objective response rate (ORR)

    ORR, defined as the rate of patients with complete response (CR) or partial response (PR), as determined locally by the investigator using RECIST v.1.1 (in all patients and HER2-low population).

    Measured: Up to 25 months

  3. Clinical benefit rate (CBR)

    CBR, defined as the rate of patients with objective response (CR or PR), or stable disease for at least 24 weeks, as determined locally by the investigator using RECIST v.1.1 (in all patients and HER2-low population).

    Measured: Up to 25 months

  4. Duration of response (DoR)

    DoR, defined as the period from the first occurrence of a documented objective response to disease progression or death from any cause, whichever occurs first, as determined locally by the investigator using RECIST v.1.1 (in all patients and HER2-low population).

    Measured: Up to 25 months

  5. Time to response (TTR)

    TTR, defined as the period from randomization date to the first objective tumor response (tumor shrinkage of ≥ 30%) observed for patients who achieved a CR or PR, as determined locally by the investigator using RECIST v.1.1 (in all patients and HER2-low population).

    Measured: Up to 25 months

  6. Time to treatment failure (TTF)

    TTF, defined as the time from randomization date to discontinuation of treatment for any reason, including progressive disease, treatment toxicity, patient choice, and death.

    Measured: Up to 25 months

  7. Time to first subsequent chemotherapy (TFSC)

    TFSC, defined as the time from randomization date to the beginning of the first subsequent chemotherapy after discontinuation of the trial regimen.

    Measured: Up to 25 months

  8. Progression free survival 2 (PFS2)

    PFS2, defined as the time from randomization to objective tumor progression on next-line treatment or death from any cause, in each treatment arm.

    Measured: Up to 25 months

  9. Time to start of first subsequent therapy or death (TFST)

    TFST, defined as the time from randomization to the earliest date of anti-cancer therapy start date following study treatment discontinuation, or death.

    Measured: Up to 25 months

  10. Best percentage of change in tumor burden

    Best percentage of change from baseline in the size of target tumor lesions, defined as the biggest decrease, or smallest increase if no decrease will be observed, as determined locally by the investigator using RECIST v.1.1.

    Measured: Up to 25 months

  11. Health-related quality-of-life (HRQoL)

    Changes in health-related quality-of-life (HRQoL) from baseline using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30).

    Measured: Up to 25 months

  12. Health-related quality-of-life (HRQoL)

    Changes in health-related quality-of-life (HRQoL) from baseline using the European Organization for Research and Treatment of Cancer (EORTC) Breast Cancer-Specific Quality of Life Questionnaire (QLQ-BR42).

    Measured: Up to 25 months

  13. Health-related quality-of-life (HRQoL)

    Changes in health-related quality-of-life (HRQoL) from baseline using the EuroQol 5-level EQ-5D version (EQ-5D-5L) index.

    Measured: Up to 25 months

  14. Incidence of Adverse Events, Serious Adverse Events and Suspected Unexpected Serious Adverse Reactions

    Number of Adverse Events (AEs), Serious Adverse Events (SAEs), and Suspected Unexpected Serious Adverse Reactions (SUSARs) according to the National Cancer Institute (NCI) CTCAE Version 5.0 (v.5.0) (Safety and Tolerability)

    Measured: Up to 25 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Jul 2024
  2. Study start30 Jun 2025
  3. Primary completionJan 2027 (estimated)
  4. Study completionJan 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Arm A: T-DXd; Arm B CDK4/6i plus endocrine therapy (ET). The physician's choice of CDK4/6i plus ET will be limited to one CDK4/6i plus fulvestrant or an aromatase inhibitor (AI). The options for CDK4/6i are palbociclib, ribociclib, and abemaciclib, the options for ET are fulvestrant, letrozole, anastrozole, and exemestane.
Masking
None (open label)
Enrolment
200 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06486883
Sponsor's protocol ID
MEDOPP556
Acronym
PONTIAC
Status last verified
Jun 2026
First submitted
17 Jun 2024
Last updated
30 Jul 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Trastuzumab deruxtecan (T-DXd, DS-8201a) and CDK4/6i plus ET in people with Advanced Breast Cancer and Advanced Breast Carcinoma, run by MedSIR at 79 sites in 10 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 28 inclusion and 33 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 30 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 79 sites in Spain, Italy, Portugal, France, Germany and 5 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact MEDSIR (+ 34 932 214 135, contact.trials@medsir.org), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-free survival (PFS) (time frame: Up to 25 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06486883.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jul 2026.

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