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Breast CancerPhase 2GeparNuevoNCT02685059

Addition of PD-L1 Antibody MEDI4736 to a Taxane-anthracycline Chemotherapy in Triple Negative Breast Cancer

A Phase 2 study testing MEDI4736 (Anti PD-L1), nab-Paclitaxel and Epirubicin in people with Breast Cancer, run by GBG Forschungs GmbH at 1 site in Germany.

Completed

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

Official record
Search all trials

Trial summary

To date no targeted agents are available to treat TNBC. Therefore chemotherapy is the only treatment option. TNBC often has a high amount of tumour infiltrating lymphocytes. Stimulating the immune cells of TNBC might therefore be an option for these patients to increase the pathological complete response. Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Breast Cancer
What is being tested?
MEDI4736 (Anti PD-L1), nab-Paclitaxel and Epirubicin
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
174 participants
Where
1 siteGermany
Study dates
Jun 2016to Mar 2018
Phase
Phase 2
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
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Written informed consent for all study according to local regulatory requirements prior to beginning specific protocol procedures.
  • Complete baseline documentation must be sent to GBG Forschungs GmbH.
  • Unilateral or bilateral primary carcinoma of the breast, confirmed histologically by core biopsy. Fine-needle aspiration alone is not sufficient. Incisional biopsy is not allowed. In case of bilateral cancer, the investigator has to decide prospectively which side will be evaluated for the primary endpoint.
  • Tumor lesion in the breast or the nodes must be measurable in two dimensions, preferably by sonography. In case of inflammatory disease, the extent of inflammation can be used as measurable lesion.
  • Patients must be in the following stages of disease: cT1b - cT4a-d irrespective of nodal involvement.
  • In patients with multifocal or multicentric breast cancer, the largest lesion should be measured.
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  • Triple negative disease with centrally confirmed ER negative/PR negative/HER-2 negative, and centrally confirmed Ki-67 value. ER negative is defined as <1% stained cells, PR negative is defined as <10% stained and HER2-negative is defined as either IHC 0/1+ or IHC 2+ and in-situ hybridisation (ISH) of either ratio <2.0 or less than 6 copies of HER2 per tumor cell. Stromal TILs will be evaluated in three groups: low immune infiltrate (0-10% stromal TILs) intermediate immune infiltrate (11-59% stromal TILs), LPBC 60-100% stromal TILs. PD-L1 status and other predefined markers will be prospectively assessed during the study. Formalin-fixed, paraffin-embedded (FFPE) breast tissue from core biopsy has therefore to be sent to the GBG central pathology laboratory prior to randomization.
  • Age >=18 years.
  • ECOG Performance status 0-1.
  • Normal cardiac function must be confirmed by ECG and cardiac ultrasound (LVEF or shortening fraction) within 3 months prior to randomization. Results must be above the normal limit of the institution.
  • Negative pregnancy test (urine or serum) within 14 days prior to randomization for all women of childbearing potential. Female subjects must either be of non-reproductive potential (ie, post-menopausal by history: >=60 years old and no menses for >=1 year without an alternative medical cause; OR history of hysterectomy, OR history of bilateral tubal ligation, OR history of bilateral oophorectomy) or must have a negative serum pregnancy test upon study entry.
  • Complete staging work-up within 3 months prior to randomization. All patients must have had breast imaging by breast ultrasound plus either bilateral mammography or breast MRI (one of those <= 21 days). All patients must have had chest X-ray (PA and lateral), abdominal ultrasound or CT scan or MRI, and bone scan (according to guidelines). In case of positive bone scan, bone X-ray is mandatory. Other tests may be performed as clinically indicated.
  • Patients must be available and compliant for central diagnostics, treatment and follow-up.
  • Laboratory requirements: Hematology, Hepatic function, Renal Function, Thyroid function

Who cannot join

  • Prior chemotherapy for any malignancy.
  • Prior radiation therapy for breast cancer.
  • Pregnant or lactating patients. Patients of childbearing potential must implement adequate non-hormonal contraceptive measures (barrier methods, intrauterine contraceptive devices, sterilization) during study treatment.
  • Inadequate general condition (not fit for dose-dense, dose-intensified anthracycline-taxane-targeted agents-based chemotherapy).
  • Previous malignant disease being disease-free for less than 5 years (except CIS of the cervix and non-melanomatous skin cancer).
  • 6. Known or suspected congestive heart failure (>NYHA I) and / or coronary heart disease, angina pectoris requiring antianginal medication, previous history of myocardial infarction, evidence of transmural infarction on ECG, uncontrolled or poorly controlled arterial hypertension (i.e. BP >140 / 90 mm Hg under treatment with at maximum two antihypertensive drugs), rhythm abnormalities requiring permanent treatment, clinically significant valvular heart disease.
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  • Mean QT interval corrected for heart rate (QTc) ≥470 ms calculated from 3 electrocardiograms (ECGs) using Bazett's Correction
  • Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis)
  • History of primary immunodeficiency
  • History of allogeneic organ transplant
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, active peptic ulcer disease or gastritis, active bleeding diatheses including any subject known to have evidence of acute or chronic hepatitis B, hepatitis C or human immunodeficiency virus (HIV).
  • Known history of previous clinical diagnosis of tuberculosis
  • Receipt of live attenuated vaccination within 30 days prior to study entry or within 30 days of receiving MEDI4736
  • Autoimmune disease and conditions (i.e. inflammatory bowel disease)
  • History of significant neurological or psychiatric disorders including psychotic disorders, dementia or seizures that would prohibit the understanding and giving of informed consent
  • Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results
  • Pre-existing motor or sensory neuropathy of a severity >= grade 2 by NCI-CTC criteria v 4.0.
  • Currently active infection.
  • Incomplete wound healing or unhealed bone fracture.
  • Definite contraindications for the use of corticosteroids
  • Known hypersensitivity reaction to one of the compounds or incorporated substances used in this protocol;
  • Concurrent treatment with:
  • chronic corticosteroids prior to study entry with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or equivalent corticosteroid.
  • other immunosuppressive medication (e.g. low dose MTX)
  • sex hormones (including hormonal contraception) prior treatment must be stopped before study entry.
  • other experimental drugs or any other anti-cancer therapy.
  • Participation in another clinical trial with any investigational, not marketed drug within 30 days prior to study entry.
  • Any previous treatment with a PD1 or PD-L1 inhibitor, including MEDI4736
  • Male patients.

Trial locations and contacts

1 site in 1 country.

Germany1 site

  • Centrum für Hämatologie und Onkologie am Bethanien-Krankenhaus

    Frankfurt am Main, Hesse, 60389

Other trials in Germany

About this study

Official title: A Randomized Phase II Study to Investigate the Addition of PD-L1 Antibody MEDI4736 to a Taxane-anthracycline Containing Chemotherapy in Triple Negative Breast Cancer (GeparNuevo)

To date no targeted agents are available to treat TNBC. Therefore chemotherapy is the only treatment option. TNBC often has a high amount of tumour infiltrating lymphocytes. Stimulating the immune cells of TNBC might therefore be an option for these patients to increase the pathological complete response. pCR is highly correlated with outcome in TNBC.

Therefore the addition of a checkpoint inhibitor in addition to chemotherapy might be an additional option for these patients.

Read the detailed description

To date no targeted agents are available to treat TNBC. Therefore chemotherapy is the only treatment option. TNBC often has a high amount of tumour infiltrating lymphocytes. Stimulating the immune cells of TNBC might therefore be an option for these patients to increase the pathological complete response. pCR is highly correlated with outcome in TNBC.

Therefore the addition of a checkpoint inhibitor in addition to chemotherapy might be an additional option for these patients.

The primary objective therefore is to compare the pathological complete response (pCR= ypT0 ypN0) rates of neoadjuvant treatment of sequential, nab-Paclitaxel followed by EC +/- the PD-L1 antibody MEDI4736 in patients with early triple negative breast cancer.

Conditions
Breast Cancer
Being tested
MEDI4736 (Anti PD-L1), Placebo, nab-Paclitaxel, Epirubicin, Cyclophosphamide
Keywords
breast cancer, Medi4736, Anti PD-L1, Nab-Paclitaxel, Placebo, triple negative
Medical subject headings
Breast Neoplasms

What participants receive

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

  • MEDI4736 (Anti PD-L1)Drug

    Also called Antibody against cell death ligand 1 (PD-L1)

    MEDI4736 1.5g total i.v. every 4 weeks

    As monotherapy for the first two weeks (0.75g absolute) (part 1) followed by:

    MEDI4736 in combination with nab-paclitaxel 125 mg/m² every week for 12 weeks (part 2) followed by

    MEDI4736 in combination with epirubicin 90mg/m² plus cyclophosphamide 600 mg/m² every 2 weeks for 4 cycles (part 3).

  • PlaceboDrug

    Placebo i.v. every 4 weeks

    As monotherapy for the first two weeks (0.75g absolute) (part 1) followed by:

    Placebo in combination with nab-paclitaxel 125 mg/m² every week for 12 weeks (part 2) followed by

    MEDI4736/Placebo in combination with epirubicin 90mg/m² plus cyclophosphamide 600 mg/m² every 2 weeks for 4 cycles (part 3).

  • nab-PaclitaxelDrug

    Also called non-solvent based taxane

    nab-Paclitaxel 125 mg/m² weekly for 12 weeks

  • EpirubicinDrug

    Also called Farmorubicin

    Epirubicin 90 mg/m² 2-weekly for 8 weeks

  • CyclophosphamideDrug

    Also called Endoxan

    Cyclophosphamide 600 mg/m² 2-weekly for 8 weeks

Study groups in NCT02685059
Study groupRoleWhat they receive
MEDI4736Experimentalpart 1: MEDI4736 (with half dose as monotherapy for the first two weeks) part 2: MEDI4736 1.5 g total for 20 weeks
Receives: Drug: MEDI4736 (Anti PD-L1)
PlaceboPlacebo comparatorpart 1: Placebo (for the first two weeks) part 2: Placebo for 20 weeks
Receives: Drug: Placebo
TaxaneActive comparatorNab-Paclitaxel 125 mg/m² weekly for 12 weeks
Receives: Drug: nab-Paclitaxel
EpirubicinActive comparatorEpirubicin 90 mg/m² 2-weekly for 8 weeks
Receives: Drug: Epirubicin
CyclophosphamideActive comparatorCyclophosphamide 600 mg/m² 2-weekly for 8 weeks
Receives: Drug: Cyclophosphamide

What is being measured

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

  1. pathological complete response (pCR= ypT0 ypN0)

    To compare the pathological complete response (pCR= ypT0 ypN0) rates of neoadjuvant treatment of sequential, nab-Paclitaxel followed by EC +/- the PD-L1 antibody MEDI4736 in patients with early triple negative breast cancer.

    Measured: 22 weeks

Secondary outcomes (10)

  1. pCR rates per arm

    To assess the pCR rates per arm separately for the stratified subpopulations.

    Measured: 22 weeks

  2. Rates of ypT0/is ypN0

    To determine the response rates of the breast tumor and axillary nodes based on physical examination and imaging tests (sonography, mammography, or MRI) after treatment in different arms.

    Measured: 22 weeks

  3. Rates of ypT0/is ypN0/+

    To determine the response rates of the breast tumor and axillary nodes based on physical examination and imaging tests (sonography, mammography, or MRI) after treatment in different arms.

    Measured: 22 weeks

  4. Rates of ypT(any) ypN0

    To determine the response rates of the breast tumor and axillary nodes based on physical examination and imaging tests (sonography, mammography, or MRI) after treatment in different arms.

    Measured: 22 weeks

  5. Rates of ypT0 ypN0/+

    To determine the response rates of the breast tumor and axillary nodes based on physical examination and imaging tests (sonography, mammography, or MRI) after treatment in different arms.

    Measured: 22 weeks

  6. Clinical response

    To assess clinical response rate after taxane in both groups.

    Measured: 22 weeks

  7. Breast conservation rate

    To determine the breast conservation rate after each treatment.

    Measured: 22 weeks

  8. Toxicity and compliance as measured by number of participants with treatment-related

    Number of participants with treatment-related adverse events CTCAE v4.0

    Measured: 22 weeks

  9. Molecular markers and gene expression

    To examine and compare pre-specified molecular markers and gene expression signatures such as tumor infiltrating lymphocytes, PD-1, PD-L1, Ki-67, etc. on core biopsies before chemotherapy, after the window phase and surgical tissue after end of chemotherapy (in %)

    Measured: 22 weeks

  10. Survival

    To determine loco-regional invasive recurrence free survival (LRRFS), distant-disease-free survival (DDFS), invasive disease-free survival (IDFS), event free survival (EFS per FDA definition) and overall survival (OS) in different arms and according to stratified subpopulations (in months)

    Measured: 22 weeks

Timeline

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

  1. First posted18 Feb 2016 (estimated)
  2. Study startJun 2016
  3. Primary completionMar 2018
  4. Study completionMar 2018

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
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
174 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02685059
Sponsor's protocol ID
GBG89
Acronym
GeparNuevo
Status last verified
Feb 2021
First submitted
14 Jan 2016
Last updated
15 Feb 2021
Results posted
No
Data monitoring committee
Yes
Individual data sharing
No

Publications

  • Loibl S, Untch M, Huober J, Schaser V, Braun M, Denkert C, Hartkopf A, Blohmer JU, Hanusch C, Link T, Reinisch M, Zahm DM, Weide R, Bjelic-Radisic V, Staib P, Tesch H, Rhiem K, Lorenz R, Rey J, Schneeweiss A. Durvalumab in Combination With Neoadjuvant Chemotherapy in Early Triple-Negative Breast Cancer: Long-Term Analysis From the GeparNuevo Trial. J Clin Oncol. 2026 Jun 10;44(17):1580-1586. doi: 10.1200/JCO-25-02311. Epub 2026 Apr 20.

    PubMed 42008768

  • Massa C, Karn T, Denkert C, Schneeweiss A, Hanusch C, Blohmer JU, Zahm DM, Jackisch C, van Mackelenbergh M, Thomalla J, Marme F, Huober J, Muller V, Schem C, Mueller A, Stickeler E, Biehl K, Fasching PA, Untch M, Loibl S, Weber K, Seliger B. Differential effect on different immune subsets of neoadjuvant chemotherapy in patients with TNBC. J Immunother Cancer. 2020 Nov;8(2):e001261. doi: 10.1136/jitc-2020-001261.

    PubMed 33199511

  • Perez-Garcia J, Soberino J, Racca F, Gion M, Stradella A, Cortes J. Atezolizumab in the treatment of metastatic triple-negative breast cancer. Expert Opin Biol Ther. 2020 Sep;20(9):981-989. doi: 10.1080/14712598.2020.1769063. Epub 2020 May 25.

    PubMed 32450725

  • Loibl S, Untch M, Burchardi N, Huober J, Sinn BV, Blohmer JU, Grischke EM, Furlanetto J, Tesch H, Hanusch C, Engels K, Rezai M, Jackisch C, Schmitt WD, von Minckwitz G, Thomalla J, Kummel S, Rautenberg B, Fasching PA, Weber K, Rhiem K, Denkert C, Schneeweiss A. A randomised phase II study investigating durvalumab in addition to an anthracycline taxane-based neoadjuvant therapy in early triple-negative breast cancer: clinical results and biomarker analysis of GeparNuevo study. Ann Oncol. 2019 Aug 1;30(8):1279-1288. doi: 10.1093/annonc/mdz158.

    PubMed 31095287

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing MEDI4736 (Anti PD-L1), nab-Paclitaxel and Epirubicin in people with Breast Cancer, run by GBG Forschungs GmbH at 1 site in Germany.

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 14 inclusion and 29 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 15 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Germany. 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. Some participants in this study may receive a placebo. 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?

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?

pathological complete response (pCR= ypT0 ypN0) (time frame: 22 weeks). 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 NCT02685059, which also lists 4 linked publications.

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 15 Feb 2021.

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