A Study of Debio 1347 Plus Fulvestrant in Patients With Metastatic Breast Cancer

Inclusion Criteria

• Males and Females Age > 18 years
• Written informed consent and authorization obtained from the subject/HIPAAappointed legal representative prior to performing any protocol-related procedures including screening evaluations
• Patients with metastatic histologically or cytologically confirmed invasive breast cancer
• Female patients of postmenopausal status. with metastatic histologically or cytologically confirmed invasive breast cancer.
• Postmenopausal status will be defined as following:
• Age ≥ 60 years
• Age 3000/ul
• Absolute neutrophil count (ANC) > 1000/ul
• Platelets > 100, 000/ul, hemoglobin > 9.0 g/dl
• Non-hematologic parameters:
• Corrected calcium value /= 2.5 g/dL
• Phosphat 4 weeks may be enrolled.
• Female subjects of childbearing potential should have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication and agree to use effective contraception. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.

Exclusion Criteria

• Prior Fulvestrant for metastatic breast cancer will be allowed for phase 1 portion but not for the phase 2 portion
• History of hypersensitivity to any of the excipients in the Debio 1347 formulation (lactose hydrate, microcrystalline cellulose, croscarmellose sodium, hydroxypropyl cellulose, sodium lauryl sulfate, and magnesium stearate).
• Other malignancies requiring active treatment in the last 6 months.
• Brain tumors and/or brain metastases unless they are asymptomatic, stable on recent imaging (not dated more than 30 days from the inclusion date), and have not required active treatment in the last 6 months.
• History and/or current evidence of endocrine alteration of calcium-phosphate homeostasis.
• History of myocardial infarction or stroke within 6 months, congestive heart failure greater than NYHA class II, unstable angina pectoris, unexplained recurrent syncope, cardiac arrhythmia requiring treatment or family history of sudden death from cardiacrelated causes.
• Baseline Frederica"s corrected QT (QTcF) interval greater than 470 msec (female) or greater than 450 msec (male), history of congenital long QT syndrome, the presence in the screening ECG of a conduction abnormality that in the opinion of the Investigator would preclude safe participation in this study.
• Concomitant use of a drug with a known risk of QTc prolongation
• Current anticoagulation therapy with therapeutic doses of warfarin (low-dose warfarin ≤ 1mg/day or low molecular-weight heparin are permitted).
• History and or current evidence of ectopic mineralisation/calcification including but not limited to the soft tissue, kidneys, intestine, myocardium and lung with the exception of calcified lymph nodes and asymptomatic coronary calcification.
• Concomitant use of high dose systemic steroids and other drugs such as calcitonin preparations, active Vitamin D3 preparations, estrogen preparations, selective estrogen receptor modulators, Vitamin K2 preparations, parathyroid hormones, phosphorus absorbers. Note, inhaled, topical steroids and low tapering doses of steroid especially in patients treated recently for brain metastases will be included.
• Corneal disease, such as bullous or band keratopathy, corneal desquamation, keratitis, corneal ulcer, or keratoconjunctivitis.
• Known infection requiring the systemic use of, for example, an antibiotic or antiviral agent.
• Known HIV, HBV or HCV infection.
• Known untreated or uncontrolled acute infection, including urinary tract infection, within 7 days of study entry.
• History of organ, bone marrow, or stem cell transplantation.
• Pregnant or lactating woman (any woman of childbearing potential who has menstruated within the year prior to enrolment will undergo pregnancy testing within 72 hours prior to receiving the first dose of st