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Early Breast CancerPhase 2PHERGAIN-2NCT04733118

Chemotherapy-Free pCR-Guided Strategy With Trastuzumab-pertuzumab and T-DM1 in HER2-positive Early Breast Cancer

A Phase 2 study testing Trastuzumab and Pertuzumab (FDC SC) and T-DM1 in people with Early Breast Cancer, run by MedSIR at 41 sites in 5 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

This is a multicenter, open-label, single-arm, one-stage, phase II study to assess the efficacy of a chemotherapy-free pathological complete response (pCR)-guided strategy with trastuzumab and pertuzumab (given as a subcutaneous fixed-dose combination) and T-DM1, for patients with previously untreated HER2-positive… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Early Breast Cancer
What is being tested?
Trastuzumab and Pertuzumab (FDC SC) and T-DM1
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
393 participants
Where
41 sitesin 5 countries
Study dates
5 Aug 2021to Mar 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 will be included in the study only if they meet ALL of the following criteria:
  • Written informed consent prior to beginning specific protocol procedures.
  • Female or male patients ≥ 18 years of age.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  • Histologically proven invasive carcinoma of the breast.
  • Tumor size must be between ≥ 5mm and ≤30mm in greatest dimension using breast MRI. Note: Although tumors between ≥ 5mm and ≤ 10mm are not considered target lesions by RECIST v1.1, we will consider these lesions as targets to follow-up.
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  • Patients must have node-negative breast cancer by clinical exam, MRI and ultrasound according to the American Joint Committee on Cancer (AJCC) 8th edition.
  • Centrally confirmed HER2[+] status with IHC score 3+.
  • Known estrogen receptor (ER) and progesterone receptor (PgR) status prior to study entry that should be performed by immunohistochemical methods according to the local institution standard protocol.
  • Patients with multifocal or multicentric breast cancer are eligible; only patients with a total number of lesions ≤ 2 are eligible and if all lesions sampled meet the inclusion criteria #5, #6, and #7. Note: If two lesions are in such proximity that it is suspected to be the same lesion, it would not be necessary to biopsy both.
  • Normal left ventricular function and diastolic function (left ventricular ejection fraction [LVEF] ≥55%) as assessed by echocardiogram or multiple-gated acquisition scan (MUGA) documented within ≤28 days prior to first dose of study treatment.
  • Adequate bone marrow, liver, and renal function:
  • Hematological: White blood cell (WBC) count > 3.0 × 109/L, absolute neutrophil count (ANC) ≥ 1.5 × 109/L, platelet count ≥ 100.0 × 109/L, and hemoglobin ≥ 10.0 g/dL (≥ 6.2 mmol/L).
  • Hepatic: total bilirubin ≤ institutional upper limit of normal (ULN) (except for Gilbert's syndrome); alkaline phosphatase (ALP) ≤ 2.5 times ULN; aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 1.5 times ULN.
  • Renal: serum creatinine ≤ 1.5 × ULN or creatinine clearance ≥ 50 mL/min/1.73 m2 for patients with creatinine levels above institutional normal.
  • International normalized ratio (INR) and activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN.
  • Patient must be accessible for treatment and follow-up.
  • Willingness and ability to provide blood samples at baseline, C3D1 before treatment infusion, pre-surgery and then after surgery: every 6 months for the first 5 years, and every year thereafter until the EoS.
  • Willingness and ability to provide tumor tissue samples at baseline and at surgery.
  • Women of childbearing potential and men with partners of childbearing potential must be willing to use one highly effective form of nonhormonal contraception or two effective forms of nonhormonal contraception by the patient and/or partner and to continue its use for the duration of study treatment and for seven months after the last dose of study treatment.
  • Note: Acceptable forms of effective contraception should include two of the following:
  • Placement of non-hormonal intrauterine device (IUD) ii. Condom with spermicidal foam/gel/film/cream/suppository iii. Diaphragm or cervical/vault caps with spermicidal foam/film/cream/suppository The above contraception is not a requirement in the case the male patient, or male partner of a female patient, is surgically sterilized, the female patient is post-menopausal or the patient remains abstinent and truly abstains from sexual activity (refrains from heterosexual intercourse).
  • Negative serum pregnancy test for premenopausal women including women who have had a tubal ligation and for women less than 12 months after the onset of menopause.

Who cannot join

  • Any patient meeting ANY of the following criteria will be excluded from the study:
  • Any previous treatment, including chemotherapy, anti-HER2 therapy, radiation therapy, or ET for invasive breast cancer (except for breast carcinoma in situ of the contralateral breast cancer, in the last five years before treatment initiation in this study).
  • HER2 disease with IHC score 0, 1+ or 2+ and in situ hybridization (ISH) positive result.
  • Evidence of metastatic disease. Note: All patients must be willing to undergo chest and pelvis computed tomography (CT)/MRI scan before enrolment to prove no evidence of metastatic disease. Bone scan will be performed at baseline only if there is suspicion of bone metastases. If a bone scan cannot be performed, an alternative is PET/CT using 18F-labeled sodium fluoride (18F-fluoride PET/CT).
  • Patients with bilateral breast cancer.
  • Known hypersensitivity reaction to any investigational or therapeutic compound or their incorporated substances.
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  • History of other malignancy within the last five years prior to first dose of study drug administration, except for curatively treated basal and squamous cell carcinoma of the skin and/or in situ cervical carcinoma.
  • Uncontrolled hypertension (systolic > 150 mm Hg and/or diastolic > 100 mm Hg) despite adequate antihypertensive treatment.
  • Serious cardiac illness or medical conditions including, but not confined to, the following:
  • History of NCI CTCAE v5.0 Grade ≥ 3 symptomatic congestive heart failure (CHF) or New York Heart Association (NYHA) Class ≥ II.
  • High-risk uncontrolled arrhythmias (i.e., atrial tachycardia with a heart rate ≥ 100/min at rest, significant ventricular arrhythmia [ventricular tachycardia], or higher-grade atrioventricular [AV]-block, such as second-degree AV-block Type 2 [Mobitz II] or third-degree AV-block).
  • Serious cardiac arrhythmia or severe conduction abnormality not controlled by adequate medication.
  • Angina pectoris requiring anti-angina medication.
  • Clinically significant valvular heart disease.
  • Evidence of transmural infarction on electrocardiogram (ECG).
  • Evidence of myocardial infarction within the last 12 months prior to study entry.
  • History of ventricular dysrhythmias or risk factors for ventricular dysrhythmias, such as structural heart disease (e.g., severe left ventricular systolic dysfunction [LVSD], left ventricular hypertrophy), coronary heart disease (symptomatic or with ischemia demonstrated by diagnostic testing), clinically significant electrolyte abnormalities (e.g., hypokalemia, hypomagnesemia, hypocalcemia), or family history of sudden unexplained death or long QT syndrome.
  • Active uncontrolled infection at the time of enrollment.
  • Current known infection with human immunodeficiency virus (HIV), hepatitis B virus, or hepatitis C virus.
  • Patients with pulmonary disease requiring continuous oxygen therapy.
  • Grade ≥2 neuropathy as per National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) version (v)5.0.
  • Previous history of bleeding diathesis.
  • Patient is currently receiving chronic treatment with corticosteroids, or another immunosuppressive agent (standard premedication for chemotherapy and local applications are allowed).
  • Major surgical procedure or significant traumatic injury within 14 days prior to study entry or anticipation of need for major surgery within the course of the study treatment.
  • Any other concurrent severe and/or uncontrolled medical condition that would contraindicate patient participation in the clinical study.
  • History of having received any investigational treatment within 28 days prior to study entry.
  • Pregnant or breast-feeding women or patients not willing to apply highly effective contraception as defined in the protocol.

Trial locations and contacts

41 sites in 5 countries.

41 sites in 5 countries

Spain25 sites

  • Centro Oncológico de Galicia

    A Coruña, 15009

  • Hospital Universitario A Coruña

    A Coruña

  • Hospital General Universitario de Alicante

    Alicante

  • Institut Català d' Oncologia Badalona (ICO)

    Badalona

  • Hospital Universitari Dexeus - Grupo Quirónsalud

    Barcelona

  • VHIO Vall d'Hebron Institute of Oncology

    Barcelona

  • Hospital Universitario de Basurto

    Bilbao, 48013

  • Consorcio Hospitalario Provincial De Castelló

    Castellon, 12002

  • Hospital Universitario Reina Sofia

    Córdoba, Cordoba, 14004

  • Hospital Universitario Clínico San Cecilio de Granada

    Granada

  • Complejo Hospitalario de Jaen

    Jaén

  • ICO L'Hospitalet - Instituto Catalán de Oncología

    L'Hospitalet de Llobregat, Barcelona, 08007

  • Complejo Asistencial Universitario de León

    León

  • Hospital Universitari Arnau de Vilanova de Lleida

    Lleida

  • Hospital Clínico San Carlos

    Madrid, 28040

  • Hospital Quirón San Camilo- Ruber Juan Bravo

    Madrid

  • Hospital Ramón y Cajal

    Madrid

  • Hospital Universitari San Joan de Reus

    Reus, Tarragona

  • Hospital Universitario Virgen del Rocio

    Seville

  • Hospital Universitario de Torrejón

    Torrejón

  • Instituto Valenciano de Oncología (IVO)

    Valencia, 46009

  • Hospital La Fe

    Valencia, 46026

  • Consorcio Hospital General de Valencia

    Valencia

  • Hospital Arnau de Vilanova de Valencia

    Valencia

  • Hospital Clinico Universitario de Valencia

    Valencia

Other trials in Spain

Italy7 sites

  • Azienda Ospedaliero Universitaria Di Bologna - Policlinico S.Orsola-Malpighi

    Bologna

  • AO Ospedale Civile Legnano

    Milan

  • Istituto Europeo di Oncologia - NC

    Milan

  • Ospedale San Gerardo

    Monza

  • Azienda Ospedaliero-Universitaria di Parma

    Parma

  • Ospedale Guglielmo da Saliceto

    Piacenza

  • Fondazione Policlinico Universitario Agostino Gemelli

    Roma

Other trials in Italy

Germany6 sites

  • Praxisnetzwerk Hämatologie und intern. Onkologie

    Cologne

  • Evangelisches Krankenhaus Bethesda

    Duisburg

  • Kliniken Essen Mitte

    Essen

  • Universitätsklinikum Essen Frauenklinik

    Essen

  • Universitätsklinikum Mannheim GmbH

    Manheim

  • Klinikum Ernst von Bergmann

    Potsdam

Other trials in Germany

Hungary2 sites

  • Békés county hospital

    Békés

  • Tolna County Balassa János Hospital

    Szekszárd

Other trials in Hungary

Bulgaria1 site

  • UMHAT Sveti Ivan Rilski EAD Department of Medical Oncology

    Sofia

Other trials in Bulgaria

About this study

Official title: Chemotherapy-Free pCR-Guided Strategy With Subcutaneous Trastuzumab-pertuzumab and T-DM1 in HER2-positive Early Breast Cancer (PHERGAIN-2)

This is a multicenter, open-label, single-arm, one-stage, phase II study to assess the efficacy of a chemotherapy-free pathological complete response (pCR)-guided strategy with trastuzumab and pertuzumab (given as a subcutaneous fixed-dose combination) and T-DM1, for patients with previously untreated HER2-positive early breast cancer.

Read the detailed description

Patients ≥ 18 years of age with previously untreated HER2 IHC 3+ invasive carcinoma according to ASCO/CAP 2018 guidelines.

Tumor size between >5 to 30 mm by breast MRI and node-negative status by clinical exam, MRI, and ultrasound. In patients with suspected axillary node involvement, a negative fine needle aspiration biopsy (FNAB) will be mandatory.

Central review for:

Breast MRI. HER2 status. Neoadjuvant treatment will consist In 8 cycles of fixed-dose subcutaneous (SC FDC) HP combination (± ET according to HR status).

urgery will be performed within 4 weeks from the last cycle of HP (sentinel node biopsy will be mandatory; subsequent axillary dissection will be performed according to local guidelines). Surgery will require free margins for any infiltrating or DCIS lesion.

Radiotherapy will be mandatory for patients with breast preservation.

Adjuvant systemic therapy will be started within 4 weeks from surgery depending on pathological report:

Arm A: pCR (breast and axilla): HP SC FDC x 10 cycles. Arm B: Residual invasive breast tumor and/or ypN0(i+), ypN0(mol+), ypN1mi: T-DM1 x 10 cycles Arm C: ypN1 to N3: T-DM1 x 10 cycles, with physician's choice chemotherapy allowed between surgery and T-DM1.

All patients with HR[+] tumors will receive adjuvant ET up to at least 5 years (ET will also be administered in association with adjuvant HP or T-DM1, with the exception of the cycles involving the use of chemotherapy in Arm C).

Being tested
Trastuzumab and Pertuzumab (FDC SC) and T-DM1
Medical subject headings
Breast Neoplasms

What participants receive

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

  • Trastuzumab and Pertuzumab (FDC SC) and T-DM1Drug

    Also called Trastuzumab emtansine, Phesgo, Kadcyla

    Patients will receive Trastuzumab and Pertuzumab as a subcutaneous fixed-dose combination (PH FDC SC) (± ET depending on HR status) for 8 3-week cycles, on day 1 only. ET will consist of letrozole for post-menopausal women or tamoxifen ± ovarian function suppression (OFS) for pre-menopausal women administered continuously. Men will receive tamoxifen.

    After completing neoadjuvant therapy, a final breast MRI will be performed 2 weeks prior to surgery. Surgery will be performed within 4 weeks after completion of the last cycle of PH FDC SC.

    Adjuvant systemic therapy will start within 4 weeks from surgery. There will be three different cohorts depending on pathological report:

    • Cohort A: PH FDC SC ± ET for 10 additional 3-week cycles
    • Cohort B: T-DM1 ± ET for 10 cycles
    • Cohort C: T-DM1 ± ET for 10 cycles, with possibility of physician's choice chemotherapy before adjuvant T-DM1.
Study groups in NCT04733118
Study groupRoleWhat they receive
Patient HER 2+ IHC 3+ExperimentalPatients ≥18 years of age with previously untreated HER2-positive (HER2[+]) (Immunohistochemistry [IHC] 3+) invasive carcinoma according to the 2018 American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) criteria and tumor size between >5 to 25 mm by breast magnetic resonance imaging (MRI) and node-negative status by clinical exam, MRI, and ultrasound. Patients must have not been previously treated with chemotherapy, anti-HER2 therapy, radiation therapy, or endocrine therapy (ET) for invasive breast cancer. Patients with metastatic disease are not eligible. In patients with suspected axillary node involvement, a negative fine needle aspiration biopsy (FNAB) will be mandatory
Receives: Drug: Trastuzumab and Pertuzumab (FDC SC) and T-DM1

What is being measured

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

  1. 3-year recurrence-free interval (3y-RFI)

    3-year recurrence-free interval (3y-RFI) defined as time from start of treatment in adjuvant setting until recurrence, new invasive disease, or death from breast cancer. Recurrence will be defined in accordance with the standardized efficacy endpoints (STEEP) criteria.

    Measured: 3 years

  2. Global health status decline

    Global health status decline rate at 1 year from start of neoadjuvant treatment, defined as the rate of patients with a ≥10% global health status decline at 1 year from start of neoadjuvant treatment as assessed by the Global Health Status/QoL EORTC-QLC-C30 scale and its breast cancer module QLQ-BR23.

    Measured: 1 year

Secondary outcomes (22)

  1. pathological complete response (pCR)

    pCR rates concerning breast and lymph nodes (pCRBREAST+LYMPH NODE) and pCR concerning breast only (pCRBREAST) in the overall population.

    Measured: after neoadjuvant treatment (8 cycles, an average of 6months)

  2. pathological complete response (pCR) according to hormone receptor (HR) status

    pCR rates according to HR status

    Measured: after neoadjuvant treatment (8 cycles, an average of 6months)

  3. Residual cancer burden (RCB)

    RCB -0, -I, -II, -III; (0:best outcome, III: worst outcome)

    Measured: after neoadjuvant treatment (8 cycles, an average of 6months)

  4. Breast-conserving surgery (BCS)

    Evaluate the rate of BCS

    Measured: after neoadjuvant treatment (8 cycles, an average of 6months)

  5. Response rate BCS

    Evaluate the correlation between final MRI-guide response rate results and breast-conserving surgery (BCS)

    Measured: after neoadjuvant treatment (8 cycles, an average of 6months)

  6. Response rate pCR

    Evaluate the correlation between final MRI- guide response rate and pCR

    Measured: after neoadjuvant treatment (8 cycles, an average of 6months)

  7. Response rate RCB

    Evaluate the correlation between final MRI -guide response rate and RCB at surgery

    Measured: after neoadjuvant treatment (8 cycles, an average of 6months)

  8. Survival rates EFS

    Analyze the event-free survival (EFS)

    Measured: 3 years and 5 years

  9. Survival rates relapse-free survival (RFS)

    Analyze RFS

    Measured: 3 years and 5 years

  10. Survival rates invasive disease-free survival (iDFS)

    Analyze iDFS

    Measured: 3 years and 5 years

  11. Survival ratesdistant relapse-free survival (DRFS)

    Analyze DRFS

    Measured: 3 years and 5 years

  12. Survival rates disease-free survival (DFS)

    Analyze DFS

    Measured: 3 years and 5 years

  13. Survival rates overall survival (OS)

    Analyze OS

    Measured: 3 years and 5 years

  14. Survival ratesbreast cancer-specific survival (BCSS).

    Analyze BCSS

    Measured: 3 years and 5 years

  15. Survival rates relapse-free interval (RFI)

    Analyze RFI

    Measured: 5 years

  16. Safety adverse events (AEs)

    Number of patients with treatment-related AEs (Grade 3 and 4 AEs and serious adverse events [SAEs]) by using the National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) v.5.0.

    Measured: Baseline up to 3 years

  17. Safety adverse events (AEs)

    Number of patients with treatment-related AEs (Grade 3 and 4 AEs and serious adverse events [SAEs]) by using the National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) v.5.0.

    Measured: Baseline up to 5 years

  18. Health-Related Quality of Life (HRQoL) - QLQ-C30

    Change from baseline in scores using the European Organisation for Research and Treatment of Cancer QoL Questionnaire Core 30 (QLQ-C30) [with 5 functional and 3 symptom scales, a Global Health Status (GHS)/QoL scale, and 6 single items], at baseline, Day 1 of cycles 2-4, then on Day 1 of each subsequent cycle starting with cycle 6, and at the end-of-treatment. Responses to all items are converted to a 0-100 scale using a standard scoring algorithm. For functional scales, higher score represents a better level of functioning; for symptom scales, a higher score represents a higher severity of symptoms.

    Measured: Baseline up to 5 years

  19. Health-Related Quality of Life (HRQoL) - QLQ-BR23

    Change from baseline in scores using the European Organisation for Research and Treatment of Cancer QLQ-BR23 [with 4 functional and 4 symptom scales], at baseline, Day 1 of cycles 2-4, then on Day 1 of each subsequent cycle starting with cycle 6, and at the end-of-treatment. Responses to all items are converted to a 0-100 scale using a standard scoring algorithm. For functional scales, higher score represents a better level of functioning; for symptom scales, a higher score represents a higher severity of symptoms.

    Measured: Baseline up to 5 years

  20. To assess the cardiac toxicity profile after 1 year of adjuvant treatment

    Adverse events of cardiotoxicity after 1 year of adjuvant treatment according to the NCI-CTCAE v.5.0.

    Measured: after 1 year of adjuvant treatment

  21. To assess the general toxicity profile according to CTCAE v.5.0.

    Toxicity and safety profile at 3 and 5 years as per NCI-CTCAE v.5.0.

    Measured: at 3 and 5 year

  22. To evaluate the ratio of patients who have needed chemotherapy.

    Ratio of patients of cohort C who will receive adjuvant chemotherapy before T-DM1.

    Measured: before T-DM1

Timeline

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

  1. First posted1 Feb 2021
  2. Study start5 Aug 2021
  3. Primary completionMar 2027 (estimated)
  4. Study completionMar 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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
393 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04733118
Sponsor's protocol ID
MedOPP293
Acronym
PHERGAIN-2
Status last verified
Apr 2026
First submitted
4 Dec 2020
Last updated
29 Apr 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 and Pertuzumab (FDC SC) and T-DM1 in people with Early Breast Cancer, run by MedSIR at 41 sites in 5 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 23 inclusion and 27 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: under way, not looking for participants, as of the sponsor's last update on 29 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 41 sites in Spain, Italy, Germany, Hungary, Bulgaria. 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?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

3-year recurrence-free interval (3y-RFI) (time frame: 3 years). 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 NCT04733118.

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 29 Apr 2026.

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