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Triple Negative Breast NeoplasmsPhase 3A-BraveNCT02926196

Adjuvant Treatment for High-risk Triple Negative Breast Cancer Patients With the Anti-PD-l1 Antibody Avelumab

A Phase 3 study testing MSB0010718C in people with Triple Negative Breast Neoplasms, run by Istituto Oncologico Veneto IRCCS at 70 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Phase III randomized trial of the anti-PD-L1 antibody avelumab as adjuvant or post-neoadjuvant treatment for high-risk triple negative breast cancer patients. The overall protocol-defined patient population will include the following two strata of patients: Stratum A - Patients who have completed treatment with… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Triple Negative Breast Neoplasms
What is being tested?
MSB0010718C
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
474 participants
Where
70 sitesin 2 countries
Study dates
17 Jun 2016to 9 Oct 2025
Phase
Phase 3
Are there results?
None posted in the registry

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

  • Non-metastatic, histologically confirmed primary invasive breast carcinoma
  • Triple negative breast cancer: hormone receptor negative (ER < 10% and PgR < 10%) and HER2 negative (IHC 0/1+ or ISH non-amplified), as defined by the local pathology laboratory. In case of discordance between pre-operative core-biopsy and the surgical sample, the receptor assessment performed on the surgical sample has to be considered for inclusion criteria evaluation.
  • Availability of a formalin-fixed, paraffin-embedded block containing tumor tissue or at least 7 unstained tumor slides.
  • Adequately excised: patients must have undergone either breast-conserving surgery or mastectomy/nipple- or skin-sparing mastectomy. The margins of the resected specimen should be free of invasive tumor and ductal carcinoma in situ (no ink on tumor). In the case of breast-conserving surgery patients with margins positive for lobular carcinoma in situ (LCIS) are eligible without additional resection. For patients who undergo mastectomy, patients with a microscopic positive deep margin are eligible, provided they will receive radiotherapy on chest wall.
  • Patients must have had axillary lymph node dissection for evaluation of pathologic nodal status. Only patients in one of the following stage categories will be eligible:
  • if 4 or more metastatic lymph nodes, any pT
Show all 53Show fewer
  • if 1 to 3 metastatic lymph nodes, pT >2 cm
  • if no metastatic lymph nodes, pT >5 cm
  • Stratum B (Post-neoadjuvant patients)
  • Non-metastatic histologically confirmed invasive breast carcinoma.
  • Triple negative breast cancer: hormone receptor negative (ER < 10% and PgR < 10%) and HER2 negative (IHC 0/1+ or ISH non-amplified), as defined by the local pathology laboratory. In case of discordance between the pre-treatment diagnostic core-biopsy and the surgical sample, the receptor assessment performed on the surgical sample has to be considered for inclusion criteria evaluation.
  • Adequately excised: patients should have undergone adequate tumor excision after preoperative chemotherapy, which means surgical removal of all clinically evident disease in the breast and lymph nodes.
  • Breast surgery: patients must have undergone either breast-conserving surgery or mastectomy/nipple- or skin-sparing mastectomy. The margins of the resected specimen should be free of invasive tumor and ductal carcinoma in situ (no ink on tumor). In the case of breast-conserving surgery patients with margins positive for lobular carcinoma in situ (LCIS) are eligible without additional resection. For patients who undergo mastectomy, patients with a microscopic positive deep margin are eligible, provided they will receive radiotherapy on chest wall.
  • Lymph node surgery:
  • Axillary dissection without sentinel node evaluation is permitted after preoperative therapy.
  • In case of positive results from a fine-needle aspiration, core biopsy, or sentinel node biopsy performed prior to preoperative therapy, additional surgical evaluation of the axilla following preoperative therapy is required.
  • If sentinel node biopsy performed before preoperative therapy was negative, no additional surgical evaluation of the axilla is required after preoperative therapy.
  • Sentinel node after preoperative therapy is allowed if no evidence of axillary node involvement was documented by ultrasonography at diagnosis. If sentinel node biopsy after preoperative therapy is negative, no further additional surgical evaluation of the axilla is required. If sentinel node biopsy performed after preoperative therapy is positive, additional surgical evaluation of the axilla is recommended.
  • Pathologic evidence of residual invasive carcinoma in the breast and/or axillary lymph nodes on the surgical specimen obtained after preoperative therapy (ypT1micN0, ypT1micN0i+, ypT0N0i+ will be excluded).
  • Clinical stage at presentation: T1-4, N0-3, M0 (Exception: Patients with T1a/bN0 tumors at presentation will not be eligible).
  • No more than 10 weeks may elapse between the date of last treatment (surgery or post-surgery chemotherapy if indicated) and the date of randomization. In case of positive margins after the first intervention requiring additional resection.
  • Availability of a formalin-fixed, paraffin-embedded block containing tumor tissue or at least 7 unstained tumor slides (tumor sample from the diagnostic core-biopsy obtained before neoadjuvant chemotherapy). In case only 7 unstained slides from the bioptic sample will be available, the investigator must ensure that the sample contains tumor tissue by performing an hematoxylin and eosin staining.
  • Exclusion criteria: Stratum A (Adjuvant patients) \& B (Post-neoadjuvant patients)
  • Stage IV breast cancer.
  • History of any prior (ipsi- and/or contralateral) invasive breast carcinoma diagnosed within 10 years.
  • Synchronous bilateral breast cancer, unless both tumors confirmed as triple negative disease.
  • History of non-breast malignancies within the 5 years prior to study entry, except for the following: Carcinoma in situ (CIS) of the cervix, CIS of the colon, Basal cell and squamous cell carcinomas of the skin.
  • Prior organ transplantation, including allogeneic stem-cell transplantation.
  • Prior or concomitant treatment with any other investigational agents.
  • Prior therapy with any antibody / drug targeting T-cell coregulatory proteins (immune-checkpoints) such as PD-1, PD-L1, or cytotoxic T-lymphocyte antigen-4 (CTLA-4).
  • Concurrent anticancer treatment (for example, cytoreductive therapy, immune therapy, or cytokine therapy except for erythropoietin)
  • Major surgery for any reason, within 4 weeks of randomization and / or if the subject has not fully recovered from the surgery within 4 weeks of randomization.
  • Concomitant treatment with all herbal (alternative) remedies with immunostimulating properties (for example, mistletoe extract) or known to potentially interfere with major organ function (for example, hypericin).
  • Subjects receiving immunosuppressive agents (such as steroids) for any reason should be tapered off these drugs before initiation of the trial treatment (with the exception of subjects with adrenal insufficiency, who may continue corticosteroids at physiologic replacement dose, equivalent to ≤ 10 mg prednisone daily).
  • Significant acute or chronic infections including, among others:
  • Known history of testing positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome.
  • Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening (positive HBV surface antigen or HCV RNA if anti-HCV antibody screening test positive).
  • Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent:
  • Subjects with diabetes type I, vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible.
  • Subjects requiring hormone replacement with corticosteroids are eligible if the steroids are administered only for the purpose of hormonal replacement and at doses ≤ 10 mg or equivalent prednisone per day.
  • Administration of steroids through a route known to result in a minimal systemic exposure (topical, intranasal, intro-ocular, or inhalation) are acceptable.
  • Administration of steroids through a route known to result in a minimal systemic exposure (topical, intranasal, intro-ocular, or inhalation) are acceptable.
  • Previous or ongoing administration of systemic steroids for the management of an acute allergic phenomenon is acceptable as long as it is anticipated that the administration of steroids will be completed in 14 days, or that the daily dose after 14 days will be ≤ 10 mg per day of equivalent prednisone.
  • Known severe hypersensitivity reactions to monoclonal antibodies (Grade ≥ 3 NCI-CTCAE v 4.03), any history of anaphylaxis, or uncontrolled asthma (that is, 3 or more features of partially controlled asthma).
  • Clinically significant (that is, active) cardiovascular disease: cerebral vascular accident /stroke (< 6 months prior to enrollment), myocardial infarction (< 6 months prior to enrollment), unstable angina, congestive heart failure (New York Heart Association Classification Class ≥ II), or serious uncontrolled cardiac arrhythmia requiring medication.
  • All other significant diseases (for example, inflammatory bowel disease), which, in the opinion of the Investigator, might impair the subject's tolerance of trial treatment.
  • Any psychiatric condition that would prohibit the understanding or rendering of informed consent.
  • Vaccination within 4 weeks of the first dose of avelumab and while on trial is prohibited except for administration of inactivated vaccines (for example, inactivated influenza vaccines).
  • Known alcohol or drug abuse.
  • Persisting toxicity related to prior therapy of Grade > 1 NCI-CTCAE v 4.03 (except for grade 2 radiodermatitis and grade 2 neuropathy).
  • Current pregnancy and/or lactation. Refusal to adopt adequate contraception methods.
  • Stratum B (Postneoadjuvant patients)
  • 1. No invasive residual disease in the breast and axilla at pathological examination after neoadjuvant chemotherapy. ypT1micN0, ypT1micN0i+, ypT0N0i+ will also be excluded.

Who cannot join

None listed.

Trial locations and contacts

70 sites in 2 countries.

70 sites in 2 countries

Italy62 sites

  • Clinica Oncologica-Ospedali Riuniti Ancona

    Ancona

  • Azienda Sanitaria Locale Di Asti

    Asti

  • Centro di Riferimento Oncologico di Aviano (CRO)

    Aviano, PN

  • Ospedale Dell'Ulss N. 1 Belluno- Ospedale S. Martino Belluno

    Belluno

  • Ospedale di Bergamo

    Bergamo, BG

  • Policlinico Sant'Orsola Malpighi

    Bologna, BO, 40138

  • Ospedale di Bellaria

    Bologna, BO

  • Ospedale Centrale Di Bolzano

    Bolzano

  • Azienda Spedali Civili di Brescia

    Brescia, BS

  • Azienda Sanitaria Locale Brindisi

    Brindisi, BR

  • Ospedale di Camposampiero

    Camposampiero, PD

  • I.R.C.C.S. - Fondazione del Piemonte per l'Oncologia

    Candiolo, TO, 10060

  • Ospedale Ramazzini

    Carpi, MO

  • Ospedale di Castelfranco Veneto

    Castelfranco Veneto, TV

  • AOU Policlinico "Vittorio. Emanuele

    Catania, CT

  • ARNAS Garibaldi,

    Catania, CT

  • P.O. Clinicizz. 'Ss. Annunziata' Chieti

    Chieti

  • Asst Lariana

    Como

  • Arcispedale S. Anna

    Cona, FE

  • A.O. Istituti Ospedalieri - Cremona

    Cremona

  • A.S.O. S.Croce e Carle di Cuneo

    Cuneo, CN, 12100

  • Azienda Unità Sanitaria Locale della Romagna

    Faenza-Ravenna-Lugo

  • AOU San Martino IST Istituto Nazionale per la Ricerca sul Cancro IRCCS

    Genova, GE, 16132

  • Ospedale Misericordia di Grosseto

    Grosseto, GR, 58100

  • Ospedale San Salvatore

    L’Aquila

  • Ospedale Lecce - 'V Fazzi' (San Cesario)- Opedale Lecce - 'V.Fazzi'

    Lecce

  • Ospedale di Livorno

    Livorno

  • ASL Lucca

    Lucca, LU

  • I.R.S.T. Srl Irccs

    Meldola

  • AOR Papardo

    Messina

  • Ospedale dell'Angelo

    Mestre, 30174

  • Istituto Nazionale dei Tumori IRCCS

    Milan, MI, 20133

  • Ospedale di Mirano

    Mirano, VE

  • Azienda Ospedaliero-Universitaria di Modena - Policlinico

    Modena, MO

  • Azienda Ospedaliera Universitaria Federico Ii

    Naples

  • Istituto Nazionale Tumori - Fondazione Pascale,

    Naples

  • Ospedale Sacro Cuore - Don Calabria

    Negrar, VR, 37042

  • AOU Maggiore della Carità - SC Oncologia Novara

    Novara

  • Istituto Oncologico Veneto IRCCS

    Padova, PD

  • AOU Policlinico di Palermo

    Palermo, PA

  • Azienda Ospedaliera Universitaria di Parma

    Parma, PR, 43126

  • .O. Ospedali Riuniti Marche Nord- Ospedale San Salvatore - Pesaro

    Pesaro Fano

  • Ospedale "Guglielmo Da Saliceto" Piacenza

    Piacenza

  • Azienda Ospedaliero-Universitaria Pisana

    Pisa

  • Azienda Ospedaliera Regionale 'S. Carlo'- Ospedale San Carlo Di Potenza

    Potenza

  • AUSL 4

    Prato, PO

  • UOC Oncologia ASUR AV3 Macerata

    Province of Macerata

  • IRCCS - Azienda Ospedaliera S.M. Nuova

    Reggio Emilia, RE, 42123

  • Presidio Ospedaliero Rimini-Santarcangel- Ospedale "Infermi" Rimini

    Rimini

  • CROB-IRCCS di Rionero in Vulture

    Rionero in Vulture, PZ

  • Azienda Ospedaliera Complesso Ospedaliero San Giovanni - Addolorata

    Roma

  • Ifo - Istituto Nazionale Tumori Regina Elena (Ire)

    Roma

  • Ospedale Fatebenefratelli

    Roma

  • Policlinico Universitario Campus Biomedico

    Roma

  • U.O.C. di Oncologia Medica Interpresidio PO S.Pertini-S Eugenio-CTO Roma

    Roma

  • UOC Oncologia Osp. S.Andrea Un. La Sapienza Roma

    Roma

  • Ao Citta' Della Salute E Della Scienza D- Osp.S. Giov.Battista Molinette

    Torino

  • Ospedale Civile Santa Chiara

    Trento, TN

  • Azienda ULSS 9 - Ca Foncello

    Treviso, TV

  • A. O. U. Santa Maria della Misericordia

    Udine, UD

  • Ospedale Di Circolo E Fondazione Macchi - Varese

    Varese

  • Policlinico G.B. Rossi

    Verona, VR

Other trials in Italy

United Kingdom8 sites

  • Royal United Hospitals Bath NHS Foundation Trust

    Bath

  • Blackpool Teaching Hospital

    Blackpool

  • Raigmore Hospital

    Inverness

  • Royal Free Hospital

    London

  • St Bartholomew's Hospital

    London

  • Hillingdon Hospitals NHS Foundation Trust and Mount Vernon Cancer Centre

    Northwood

  • Nottingham City Hospital

    Nottingham

  • Southampton General Hospital

    Southampton

Other trials in United Kingdom

About this study

Official title: Adjuvant Treatment for High-risk Triple Negative Breast Cancer Patients With the Anti-PD-l1 Antibody Avelumab: A Phase III Randomized Trial. Sponsor: Dipartimento di Scienze Chirurgiche, Oncologiche e Gastroenterologiche, Università di Padova

Phase III randomized trial of the anti-PD-L1 antibody avelumab as adjuvant or post-neoadjuvant treatment for high-risk triple negative breast cancer patients. The overall protocol-defined patient population will include the following two strata of patients:

  • Stratum A - Patients who have completed treatment with curative intent including surgery of the primary tumor followed by adjuvant chemotherapy .
  • Stratum B - Patients who have completed treatment with curative intent including neoadjuvant chemotherapy followed by surgery of the primary tumor and (if indicated) further adjuvant chemotherapy.
Read the detailed description
  • to determine whether 1 year of adjuvant Avelumab improves disease-free survival (DFS) compared to observation in patients with high-risk primary triple negative breast cancer who have completed treatment with curative intent including surgery of the primary tumor and neo- or adjuvant chemotherapy (Stratum A [surgery of the primary tumor followed by adjuvant chemotherapy] and Stratum B [neoadjuvant chemotherapy followed by surgery] combined).
  • to determine whether 1 year of adjuvant Avelumab improves disease-free survival (DFS) compared to observation in patients with high-risk primary triple negative breast cancer who have completed treatment with curative intent including neoadjuvant chemotherapy followed by surgery (Stratum B).
  • to determine whether Avelumab improves overall survival (OS) compared to observation in patients with high-risk primary triple negative breast cancer who have completed treatment with curative intent including surgery of the primary tumor and neo- or adjuvant chemotherapy.
  • to determine whether 1 year of adjuvant Avelumab improves disease-free survival (DFS) compared to observation in PD-L1-positive (as determined by a companion diagnostic test under development) patients with high-risk primary triple negative breast cancer who have completed treatment with curative intent including surgery of the primary tumor and neo- or adjuvant chemotherapy.
Being tested
MSB0010718C
Keywords
ER-Negative, PR-Negative, HER2-Negative
Medical subject headings
Triple Negative Breast Neoplasms

What participants receive

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

  • MSB0010718CDrug

    Also called Avelumab

    MSB0010718C-Avelumab is formulated as vials of 200 mg strength for IV administration

Study groups in NCT02926196
Study groupRoleWhat they receive
Arm AvelumabExperimentalAvelumab 10 mg/kg I.V. q2w for 1 year (52 weeks)
Receives: Drug: MSB0010718C
Arm ObservationNo interventionObservation as per guidelines

What is being measured

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

  1. Disease free survival

    DFS is defined as the time from randomization to locoregional invasive recurrence, second primary invasive breast cancer, other second primary cancer (excluding in-situ cancers), distant metastasis or death from any cause.

    Measured: Up to 5 years after randomization

  2. Disease free survival in PD-L1-positive patients

    DFS is defined as the time from randomization to locoregional invasive recurrence, second primary invasive breast cancer, other second primary cancer (excluding in-situ cancers), distant metastasis or death from any cause.

    Measured: Up to 5 years after randomization

Secondary outcomes (2)

  1. Overall survival

    Overall survival is defined as the time from randomization to death from any cause

    Measured: Up to 5 years after randomization

  2. Safety profile

    Toxicity will be assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI -CTCAE), version 4.

    Measured: From Baseline up to 5 years after randomization

Timeline

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

  1. First posted6 Oct 2016 (estimated)
  2. Study start17 Jun 2016
  3. Primary completionJun 2024
  4. Study completion9 Oct 2025

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 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
474 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02926196
Sponsor's protocol ID
A-BRAVE-Trial
Other IDs
2016-000189-45, 2016
Acronym
A-Brave
Status last verified
Mar 2024
First submitted
5 Oct 2016
Last updated
12 Dec 2025
Results posted
No

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing MSB0010718C in people with Triple Negative Breast Neoplasms, run by Istituto Oncologico Veneto IRCCS at 70 sites in 2 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 53 inclusion and 0 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: finished, as of the sponsor's last update on 12 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 70 sites in Italy, United Kingdom. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Disease free survival (time frame: Up to 5 years after randomization). 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 NCT02926196.

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 12 Dec 2025.

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