The study has a phase Ib and a phase II part.
- The phase Ib aims to evaluate the safety and tolerability of durvalumab in combination
with a dose- dense EC regimen in a neoadjuvant setting for early breast cancer.
- The phase II aims to explore the efficacy of durvalumab in combination with a dose-dense
EC regimen in a neoadjuvant setting for early breast cancer.
- Written informed consent and any locally-required authorization (EU Data Privacy
Directive in the EU) obtained from the subject prior to performing any
protocol-related procedures, including screening evaluations
- Female and male aged > 18 years at time of study entry.
- Patient has T1-T4 any N, M0, operable breast cancer
- Confirmed invasive ductal, lobular, mixed or medullary breast carcinoma
- TNBC defined as negative oestrogen and progesterone receptors as per local laboratory
testing and negative HER2 defined as negative ISH test or an IHC status of 0 or 1+ as
per local laboratory testing
- Luminal B HER2 negative BC defined as positive oestrogen and/or progesterone
receptors, a negative HER2 defined as negative ISH test or an IHC status of 0 or 1+ as
per local laboratory testing and a Ki67 > 14%.
- World Health Organisation (WHO) performance status of 0 or 1
- Adequate normal organ and marrow function as defined below:
1. Haemoglobin ≥ 9.0 g/dL
2. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L (> 1500 per mm3)
3. Platelet count ≥ 100 x 109/L (>100,000 per mm3)
4. Serum bilirubin ≤ 1.5 x institutional upper limit of normal (ULN).
5. AST (SGOT)/ALT (SGPT) ≤ 2.5 x institutional upper limit
6. Serum creatinine CL>40 mL/min
- Normal cardiac function must be confirmed by ECG and cardiac function assessed by US
imagery, radionucleotide ventriculography or MUGA, 4 weeks prior to randomization.
Results must be above the normal limit of the institution
- Women must either be postmenopausal or must have a negative serum pregnancy test 14
days upon study entry.
- For a woman of childbearing potential, an effective method of birth control must be
- Men must use 2 effective contraceptive measures or male sterilization with female
partners of childbearing potential or pregnant female partners, or they must remain
abstinent during the treatment period and for at least 6 months after the last dose of
the study treatment.
- Subject is willing and able to comply with the protocol for the duration of the study
including undergoing treatment and scheduled visits and examinations including follow
- Subject accepts planned biological samples collection and their use for the trial
- Involvement in the planning and/or conduct of the study
- Previous enrolment in the present study
- Participation in another clinical study with an investigational product during the
last 4 weeks
- Patient has locally recurrent or metastatic invasive BC
- History of another primary malignancy except for:
1. Malignancy treated with curative intent and with no known active disease ≥5 years
before the first dose of study drug
2. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence
3. Adequately treated carcinoma in situ without evidence of disease eg, cervical
cancer in situ or BC in situ.
- Patient has received any systemic therapy (e.g. chemotherapy, targeted therapy,
immunotherapy) or radiotherapy for current breast cancer disease
- Whatever the indication, receipt of a last dose of anti-cancer therapy (chemotherapy,
immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor
embolization, monoclonal antibodies, other investigational agent) ≤ 21 days prior to
the first dose of study drug
- Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab
- Any prior Grade ≥3 immune-related adverse event (irAE) while receiving any previous
immunotherapy agent, or any unresolved irAE >Grade 1
- Current or prior use of immunosuppressive medication within 28 days before the first
dose of durvalumab, 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 an equivalent corticosteroid
- Mean QT interval corrected for heart rate (QTc) ≥470 ms calculated from
electrocardiograms (ECGs) using Fridericia's Correction
- 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 two
antihypertensive drugs), rhythm abnormalities requiring permanent treatment,
clinically significant valvular heart disease.
- Active or prior documented autoimmune disease within the past 2 years NOTE: Subjects
with vitiligo, Grave's disease, or psoriasis not requiring systemic treatment (within
the past 2 years) are not excluded.
- Active or prior documented inflammatory bowel disease (e.g., Crohn's disease,
- History of primary immunodeficiency
- History of allogeneic organ transplant
- History of hypersensitivity to durvalumab or any excipient
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable
angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active
bleeding diatheses, any subject known to have evidence of acute or chronic hepatitis
B, hepatitis C or human immunodeficiency virus (HIV), or psychiatric illness/social
situations that would limit compliance with study requirements or compromise the
ability of the subject to give written informed consent
- Subjects with uncontrolled seizures.
- Known history of active tuberculosis
- Anticipation that a live attenuated vaccine will be required during the period from 30
days prior to the first planned durvalumab administration (e.i. week 18 and week 14
after study entry for the phase Ib and phase II respectively) to 5 months of
durvalumab discontinuation. Influenza vaccination (inactivated forms only but not live
attenuated forms) should be given during influenza season only (approximately October
- Female subjects who are pregnant, breast-feeding or female patients of reproductive
potential who are not employing an effective method of birth control
- Men with female partners of childbearing potential or pregnant female partners who are
not employing an effective method of birth control
- Any condition that, in the opinion of the investigator, would interfere with
evaluation of study treatment or interpretation of patient safety or study results