PHESGO Maintenance After T-DXd Short Induction for HER2+ Unresectable Locally Recurrent or Metastatic Breast Cancer

NCT06172127 | Active Not Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: MEDOPP5622023-507306-13-00MO44772
• Study Type: interventional
• Target: 165
• Locations: 5 countries
• Sites: 36

Brief Summary

DEMETHER is a phase II trial exploring the maintenance of trastuzumab and pertuzumab fixed dose combination (FDC) for subcutaneous administration (SC, PHESGO) following trastuzumab deruxtecan (T-DXd) as induction treatment for HER2-positive unresectable locally recurrent or metastatic breast cancer (MBC) patients.

Conditions

HER2-positive Breast Cancer

Keywords

HER2+ Breast Cancer; Unresectable Locally Advanced Breast Cancer; Metastatic Breast Cancer; PHESGO; Pertuzumab and Trastuzumab; T-DXd

Outcome Measures

Primary Outcomes (2)

• 1-year PFS rate

  To determine the rate of patients with absence of disease progression or death from any cause at 1 year after the treatment initiation with T-DXd followed by PHESGO, as determined locally by the investigator using RECIST v.1.1

  Baseline up to 12 months

• 3-year OS rate

  To determine the rate of patients alive at 3 years after treatment initiation with T-DXd followed by PHESGO.

  Through study completion, an average of 36 months

Secondary Outcomes (9)

• Global PFS rate

  Through study completion, an average of 36 months

• Global OS rate

  Through study completion, an average of 36 months

• Objective response rate (ORR)

  Through study completion, an average of 36 months

• Clinical benefit rate (CBR)

  Through study completion, an average of 36 months

• Time to response (TTR)

  Through study completion, an average of 36 months

Other Outcomes (6)

• Efficacy endpoints according to protein expression status on baseline tissue samples

  Through study completion, an average of 36 months

• Efficacy endpoints according to circulating tumor DNA (ctDNA) level changes in blood samples

  Through study completion, an average of 36 months

• Efficacy endpoints according to mutational profiling on baseline tissue samples

  Through study completion, an average of 36 months

Study Arms (1)

T-DXd induction treatment phase followed by PHESGO maintenance treatment phase

EXPERIMENTAL

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.

Drug: Trastuzumab deruxtecan; Drug: Phesgo 1,200 MG / 600 MG / 30,000 UNT Per 15 ML Injection; Drug: Phesgo 600 MG / 600 MG / 20,000 UNT in 10 mL Injection

Interventions

Trastuzumab deruxtecan DRUG

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.

Also known as: T-DXd

T-DXd induction treatment phase followed by PHESGO maintenance treatment phase

Phesgo 1,200 MG / 600 MG / 30,000 UNT Per 15 ML Injection DRUG

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.

Also known as: PHESGO, Pertuzumab-Trastuzumab FDC SC

T-DXd induction treatment phase followed by PHESGO maintenance treatment phase

Phesgo 600 MG / 600 MG / 20,000 UNT in 10 mL Injection DRUG

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.

Also known as: PHESGO, Pertuzumab-Trastuzumab FDC SC

T-DXd induction treatment phase followed by PHESGO maintenance treatment phase

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• To be eligible to participate in this trial, an individual must meet ALL the following criteria:
• 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.
• Male or female patients ≥ 18 years of age at the time of signing ICF.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
• Life expectancy of ≥ 12 weeks at screening.
• 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.
• Must have known estrogen receptor (ER) and progesterone receptor (PgR) status locally determined prior to study entry.
• 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.
• Evaluable disease as per Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST v.1.1) criteria.
• No prior chemotherapy and/or HER2-targeted therapy for advanced disease (one prior line of endocrine therapy is allowed for MBC).
• 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.
• Adequate hematologic and organ function, defined by the following:
• 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.
• 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).
• Renal: Creatinine clearance ≥ 50 mL/min as determined by Cockcroft Gault (using actual body weight).

You may not qualify if:

• An individual who meets ANY of the following criteria will be excluded from participation in this trial:
• Current participation in another therapeutic clinical trial, except other translational studies.
• Treatment with approved or investigational cancer therapy within 14 days prior to initiation of study drugs.
• Has previously been treated with T-DXd in the adjuvant or neoadjuvant setting.
• 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.
• 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.
• Known allergy or hypersensitivity reaction to any investigational medicinal products (IMPs) or their incorporated substances.
• 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 14 days 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 severe conduction abnormalities including, but not confined, to any of the following:
• 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.
• Poorly controlled hypertension (i.e., systolic blood pressure ≥ 180 mmHg or diastolic blood pressure ≥ 100 mmHg).
• Symptomatic pericarditis.
• Left ventricular ejection fraction (LVEF) \< 55 % as determined by multigated acquisition (MUGA) scan or echocardiogram (ECHO).

Sponsors & Collaborators

• MedSIR: lead
• Hoffmann-La Roche: collaborator

Study Sites (36)

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Northwell Health

New York, New York, 11040, United States

Location

Institute Paoli Calmettes

Marseille, France

Location

Hopital Europeen Georges Pompidou

Paris, France

Location

Hôpital Tenon AP-HP

Paris, France

Location

Marienhospital Bottrop GmbH Klinik für Gynäkologie und Geburtshilfe

Bottrop, 46236, Germany

Location

Kliniken Essen Mitte

Essen, Germany

Location

Mammazentrum HH

Hamburg, 20357, Germany

Location

Klinikum der Universität München

München, Germany

Location

Humanitas Gavazzeni

Bergamo, Italy

Location

Instituto Europeo di Oncologia

Milan, Italy

Location

University Hospital Maggiore della Carita

Novara, Italy

Location

Fondazione Policlinico Universitario Agostino Gemelli

Roma, Italy

Location

Hospital Universitario Virgen del Rocío

Seville, Sevilla, Spain

Location

Hospital del Vinalopó

Alicante, Spain

Location

Hospital General Universitario Dr. Balmis (Alicante)

Alicante, Spain

Location

Hospital Clínic i Provincial de Barcelona

Barcelona, Spain

Location

Hospital Universitari Dexeus

Barcelona, Spain

Location

Institut Català d' Oncologia L'Hospitalet (ICO)

Barcelona, Spain

Location

Hospital Universitario de Basurto

Bilbao, Spain

Location

Hospital Provincial de Castellón

Castellon, Spain

Location

Hospital Universitario Reina Sofía

Córdoba, Spain

Location

Hospital Universitario Clínico San Cecilio de Granada

Granada, Spain

Location

Hospital Universitario de León

León, Spain

Location

Hospital Beata María Ana

Madrid, Spain

Location

Hospital Clínico San Carlos

Madrid, Spain

Location

Hospital Universitario La Paz

Madrid, Spain

Location

Hospital Universitario Ramón y Cajal

Madrid, Spain

Location

MD Anderson Cancer Center Madrid

Madrid, Spain

Location

Hospital Universitario Virgen de la Victoria

Málaga, Spain

Location

Hospital Quirónsalud Sagrado Corazón

Seville, Spain

Location

Hospital Universitario Virgen Macarena

Seville, Spain

Location

Consorci Hospital General Universitari de València

Valencia, Spain

Location

Hospital Arnau de Vilanova de Valencia

Valencia, Spain

Location

Hospital Clínico Universitario de Valencia

Valencia, Spain

Location

Instituto Valenciano de Oncología (IVO)

Valencia, Spain

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

trastuzumab deruxtecan; Injections

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• Javier Cortés, MD, PhD

  Institute of Breast Cancer, Quirón Group, Barcelona (Spain)

  PRINCIPAL INVESTIGATOR

• Antonio Llombart-Cussac, MD

  Arnau de Vilanova Hospital, Valencia (Spain)

  PRINCIPAL INVESTIGATOR

• José M Pérez-García, MD

  International Breast Cancer Center (Spain)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Single arm, non-comparative, phase 2 short induction treatment phase followed by maintenance treatment phase clinical trial

Study Record Dates

• First Submitted: November 28, 2023
• First Posted: December 15, 2023
• Study Start: July 22, 2024
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): June 1, 2029
• Last Updated: April 29, 2026

Record last verified: 2026-04

Locations

US (2); IT (4); ES (23); FR (3); DE (4)