PHESGO Maintenance After T-DXd Short Induction for HER2+ Unresectable Locally Recurrent or Metastatic Breast Cancer
NCT ID: NCT06172127
Last Updated: 2025-07-29
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
PHASE2
165 participants
INTERVENTIONAL
2024-07-22
2029-05-31
Brief Summary
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Detailed Description
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Upon meeting all selection criteria, a total of 165 participants will be enrolled. Participants with no prior chemotherapy or HER2-targeted therapy for advanced or MBC (one prior line of endocrine therapy is allowed for MBC) will be eligible. Participants who have received neoadjuvant or adjuvant chemotherapy will be eligible, with a DFI from completion of systemic chemotherapy to advanced or metastatic diagnosis of \> 12 months.
Patients will continue study treatment until end of treatment (EoT) defined as the date of disease progression, death, discontinuation from the study treatment for any other reason, or up to 3 years (36 months) after T-DXd initiation, whichever occurs first. After discontinuation, all participants will undergo a safety visit at 28 (± 7 days) days after last treatment dose in order to follow up toxicities and changes in concomitant medication. Patients discontinuing the study treatment at any time will enter a post-treatment follow-up period during which survival and subsequent anticancer therapy information will be collected every 3 months (± 7 days) from the safety visit until death, lost to follow-up, elective withdrawal from the study, or the end of study (EoS), whichever occurs first.
The main objectives of DEMETHER study are to determine the efficacy of induction treatment with T-DXd followed by PHESGO as maintenance therapy in terms of progression-free survival (PFS) rate at 1 year and overall survival (OS) rate at 3 years.
End of study (EoS) is defined as the last data collection point at the last participant's safety visit and occur 36 months + 28 days (± 7 days) after the last patient included in the study initiates T-DXd treatment, unless premature termination of the study.
Conditions
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Study Design
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NA
SINGLE_GROUP
TREATMENT
NONE
Study Groups
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T-DXd induction treatment phase followed by PHESGO maintenance treatment phase
All patients will receive a 6-cycle induction phase with T-DXd 5.4 mg/kg body weight administered as an intravenous (IV) infusion on day 1 (D1) of each 21-day cycle (Q3W).
Participants may continue with PHESGO if T-DXd is discontinued prematurely due to unacceptable toxicity prior to disease progression and following recovering to Grade ≤ 1 toxicity, to Grade 0 in case of ILD/pneumonitis, or to Grade 2 for alopecia/other toxicities not considered a safety risk. If any T-DXd unacceptable toxicity occurs during the first 6 cycles of induction phase with T-DXd, participants may receive taxane-based chemotherapy concomitantly with PHESGO treatment at the discretion of the investigator.
During the maintenance phase, all participants will receive PHESGO with a loading dose of 1200 mg pertuzumab/600 mg trastuzumab as a SC injection for 8 minutes on D1 of the first 21-day cycle, and with a maintenance dose of 600 mg pertuzumab/600 mg trastuzumab as a SC Q3W.
Trastuzumab deruxtecan
10 mL type 1 amber borosilicate glass vial sealed with a fluoro-resin laminated butyl rubber stopper, and a polypropylene/aluminium yellow flip-off crimp cap. One vial of powder for concentrate for solution for IV infusion contains 100 mg of T-DXd. The drug product also contains L-histidine, L-histidine hydrochloride monohydrate, Sucrose, and Polysorbate 80.
Phesgo 1,200 MG / 600 MG / 30,000 UNT Per 15 ML Injection
20 mL type I borosilicate glass vial tapered with fluororesin-laminated rubber stopper sealed with aluminum and covered by a cool green plastic flip-off cap, containing 15 mL solution of 1200 mg of pertuzumab and 600 mg of trastuzumab.
Phesgo 600 MG / 600 MG / 20,000 UNT in 10 mL Injection
15 mL type I borosilicate glass vial tapered with fluororesin-laminated rubber stopper sealed with aluminum and covered by a cool green plastic flip-off cap, containing 10 mL solution of 600 mg of pertuzumab and 600 mg of trastuzumab.
Interventions
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Trastuzumab deruxtecan
10 mL type 1 amber borosilicate glass vial sealed with a fluoro-resin laminated butyl rubber stopper, and a polypropylene/aluminium yellow flip-off crimp cap. One vial of powder for concentrate for solution for IV infusion contains 100 mg of T-DXd. The drug product also contains L-histidine, L-histidine hydrochloride monohydrate, Sucrose, and Polysorbate 80.
Phesgo 1,200 MG / 600 MG / 30,000 UNT Per 15 ML Injection
20 mL type I borosilicate glass vial tapered with fluororesin-laminated rubber stopper sealed with aluminum and covered by a cool green plastic flip-off cap, containing 15 mL solution of 1200 mg of pertuzumab and 600 mg of trastuzumab.
Phesgo 600 MG / 600 MG / 20,000 UNT in 10 mL Injection
15 mL type I borosilicate glass vial tapered with fluororesin-laminated rubber stopper sealed with aluminum and covered by a cool green plastic flip-off cap, containing 10 mL solution of 600 mg of pertuzumab and 600 mg of trastuzumab.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
1. Patient must be capable to understand the purpose of the study and have signed written informed consent form (ICF) prior to beginning specific protocol procedures.
2. Male or female patients ≥ 18 years of age at the time of signing ICF.
3. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
4. Life expectancy of ≥ 12 weeks at screening.
5. Evidence of HER2-overexpressing tumor status confirmed by any MEDSIR's designated central lab or patient has a pathology report confirming HER2-overexpression by local testing, preferably on the most recent available metastatic sample. In the latest case, tumor tissue or blood must be sent to any MEDSIR's designated central lab for confirmation of HER2 status. Analysis of the primary tumor sample will be accepted if the metastatic tissue is inaccessible.
6. Must have known estrogen receptor (ER) and progesterone receptor (PgR) status locally determined prior to study entry.
7. Unresectable locally recurrent or MBC documented by computerized tomography (CT) scan or magnetic resonance imaging (MRI) that is not amenable to resection with curative intent.
8. Evaluable disease as per Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST v.1.1) criteria.
9. Willingness and ability to provide the most recently available formalin-fixed paraffin-embedded (FFPE) tumor tissue blocks at the time of the inclusion (mandatory). If archival tissue is not available, a newly obtained baseline biopsy of an accessible tumor lesion is required prior to start of study treatment.
10. No prior chemotherapy and/or HER2-targeted therapy for advanced disease (one prior line of endocrine therapy is allowed for MBC).
11. May have received adjuvant or neoadjuvant chemotherapy and/or HER2-targeted therapy before study treatment initiation, with a disease-free interval (DFI) from completion of the systemic treatment (excluding hormonal therapy) to metastatic diagnosis of at least 12 months.
12. Adequate hematologic and organ function, defined by the following:
1. Hematological (without platelet, red blood cell transfusion, and/or granulocyte colony-stimulating factor support within seven 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 (Hb) ≥ 9.0 g/dL.
2. Hepatic: Serum albumin ≥ 2.5 g/dL; total bilirubin ≤ 1.5 times the upper limit of normal (x ULN) (≤ 3 x ULN in patients with known history of Gilbert's disease); alkaline phosphatase (ALP) ≤ 2.5 x ULN (≤ 5 × ULN in patients with liver and/or bone metastases); aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 1.5 x ULN (≤ 3 x ULN in patients with liver metastases).
3. Renal: Creatinine clearance ≥ 50 mL/min as determined by Cockcroft Gault (using actual body weight).
4. Coagulation: International normalized ratio or prothrombin time and either partial thromboplastin or activated partial thromboplastin time ≤ 1.5 × ULN.
13. Resolution of all acute toxic effects of prior anticancer therapy to grade ≤ 1 as determined by the NCI-CTCAE v.5.0 criteria (except for alopecia or other toxicities not considered a safety risk for the patient at Investigator's discretion).
14. For 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, agreement to remain abstinent (refrain from heterosexual intercourse) or use one highly effective method of birth control or two effective contraceptive methods, as defined in the protocol from the time of screening until 7 months after the last dose of study treatments. Female patients must agree to refrain from egg cell donation and breastfeeding during this same period.
15. Male participants who intend to be sexually active with a female partner of childbearing potential must be surgically sterile or use highly effective contraceptive methods, or two effective contraceptive methods, as defined in the protocol from the time of screening until 4 months after the last dose of T-DXd or 7 months after the last dose of PHESGO to prevent pregnancy in a partner. Male participants must not donate or bank sperm during this same period. Not engaging in heterosexual activity (sexual abstinence) for the duration of the study and drug washout period is an acceptable practice if this is the preferred usual lifestyle of the participant the last dose of study treatments.
16. Patient must be accessible for treatment and follow-up.
Exclusion Criteria
1. Current participation in another therapeutic clinical trial, except other translational studies.
2. Treatment with approved or investigational cancer therapy within 14 days prior to initiation of study drugs.
3. Has previously been treated with T-DXd in the adjuvant or neoadjuvant setting.
4. Known active uncontrolled or symptomatic central nervous system (CNS) metastases and/or leptomeningeal disease as indicated by clinical symptoms, cerebral edema, and/or progressive growth.
Note: Patients with a history of CNS metastases are eligible if they have been previously treated with local therapy, are clinically stable, and off anticonvulsants and steroids for at least 14 days before the first dose of study treatment.
5. Concurrent malignancy or malignancy within 5 years of study enrollment with the exception of carcinoma in situ of the cervix, non-melanoma skin carcinoma, or stage I uterine cancer. For other cancers considered to have a low risk of recurrence, discussion with the Sponsor's Medical Monitor is required.
6. Known allergy or hypersensitivity reaction to any investigational medicinal products (IMPs) or their incorporated substances.
7. 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.
8. Major surgical procedure or significant traumatic injury within 14 days before the first dose of study treatment or anticipation of need for major surgery within the course of the study treatment.
9. Has an active cardiac disease or a history of cardiac dysfunction or severe conduction abnormalities including, but not confined, to any of the following:
1. Unstable angina pectoris, documented myocardial infarction, or symptomatic cardiac heart failure (CHF) (New York Heart Association \[NYHA\] Class II-IV) within six months prior to study entry.
2. Poorly controlled hypertension (i.e., systolic blood pressure ≥ 180 mmHg or diastolic blood pressure ≥ 100 mmHg).
3. Symptomatic pericarditis.
4. Left ventricular ejection fraction (LVEF) \< 55 % as determined by multigated acquisition (MUGA) scan or echocardiogram (ECHO).
5. 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, asymptomatic sustained ventricular tachycardia, or higher-grade atrioventricular \[AV\]-block, such as second-degree AV-block Type 2 \[Mobitz 2\] or third-degree AV-block). Participants with atrial fibrillation controlled by medication or arrhythmias controlled by pacemakers will be permitted to enroll.
6. 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 ECG.
7. 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.
8. Congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death under 40 years of age in first-degree relatives.
10. Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder (e.g., pulmonary emboli within three months of the study enrolment, severe asthma, severe chronic obstructive pulmonary disease \[COPD\], 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.
11. 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.
12. Pregnant or lactating women or patients not willing to apply highly effective contraception as defined in the protocol.
13. 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 antibody \[HBsAg\] test and a positive hepatitis B core antibody \[HBcAb\] test, accompanied by a negative HBV DNA test) are eligible. Patients positive for HCV antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA.
14. Has active primary immunodeficiency, known human immunodeficiency virus (HIV) infection.
15. Other active uncontrolled infection at the time of enrollment.
16. Receipt of live or attenuated vaccine within 30 days prior to the first dose of study treatment.
17. 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.
18. Has any other concurrent severe and/or uncontrolled medical condition that would, in the Investigator's judgment contraindicate patient participation in the clinical study.
19. Known substance abuse or any other concurrent severe and/or uncontrolled medical condition that would, in the investigator's judgment, contraindicate patient participation.
20. Inability or unwillingness to comply with study and follow-up procedures in the opinion of the Investigator.
18 Years
ALL
No
Sponsors
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Hoffmann-La Roche
INDUSTRY
MedSIR
OTHER
Responsible Party
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Principal Investigators
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Javier Cortés, MD, PhD
Role: PRINCIPAL_INVESTIGATOR
Institute of Breast Cancer, Quirón Group, Barcelona (Spain)
Antonio Llombart-Cussac, MD
Role: PRINCIPAL_INVESTIGATOR
Arnau de Vilanova Hospital, Valencia (Spain)
José M Pérez-García, MD
Role: PRINCIPAL_INVESTIGATOR
International Breast Cancer Center (Spain)
Locations
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Dana-Farber Cancer Institute
Boston, Massachusetts, United States
Northwell Health
New York, New York, United States
Institute Paoli Calmettes
Marseille, , France
Hopital Europeen Georges Pompidou
Paris, , France
Hôpital Tenon AP-HP
Paris, , France
Marienhospital Bottrop GmbH Klinik für Gynäkologie und Geburtshilfe
Bottrop, , Germany
Kliniken Essen Mitte
Essen, , Germany
Mammazentrum HH
Hamburg, , Germany
Klinikum der Universität München
München, , Germany
Humanitas Gavazzeni
Bergamo, , Italy
Instituto Europeo di Oncologia
Milan, , Italy
University Hospital Maggiore della Carita
Novara, , Italy
Fondazione Policlinico Universitario Agostino Gemelli
Roma, , Italy
Hospital del Vinalopó
Alicante, , Spain
Hospital General Universitario Dr. Balmis (Alicante)
Alicante, , Spain
Hospital Clínic i Provincial de Barcelona
Barcelona, , Spain
Hospital Universitari Dexeus
Barcelona, , Spain
Institut Català d' Oncologia L'Hospitalet (ICO)
Barcelona, , Spain
Hospital Universitario de Basurto
Bilbao, , Spain
Hospital Provincial de Castellón
Castellon, , Spain
Hospital Universitario Reina Sofía
Córdoba, , Spain
Hospital Universitario Clínico San Cecilio de Granada
Granada, , Spain
Hospital Universitario de León
León, , Spain
Hospital Beata María Ana
Madrid, , Spain
Hospital Clínico San Carlos
Madrid, , Spain
Hospital Universitario La Paz
Madrid, , Spain
Hospital Universitario Ramón y Cajal
Madrid, , Spain
MD Anderson Cancer Center Madrid
Madrid, , Spain
Hospital Universitario Virgen de la Victoria
Málaga, , Spain
Hospital Quirónsalud Sagrado Corazón
Seville, , Spain
Hospital Universitario Virgen del Rocío
Seville, , Spain
Hospital Universitario Virgen Macarena
Seville, , Spain
Consorci Hospital General Universitari de València
Valencia, , Spain
Hospital Arnau de Vilanova de Valencia
Valencia, , Spain
Hospital Clínico Universitario de Valencia
Valencia, , Spain
Instituto Valenciano de Oncología (IVO)
Valencia, , Spain
Countries
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Central Contacts
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Other Identifiers
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2023-507306-13-00
Identifier Type: OTHER
Identifier Source: secondary_id
MO44772
Identifier Type: OTHER
Identifier Source: secondary_id
MEDOPP562
Identifier Type: -
Identifier Source: org_study_id
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