CB-103 Plus NSAI In Luminal Advanced Breast Cancer

Inclusion Criteria

• •1. Signed the informed consent form (ICF) prior to any study-related activities.
• •2. Female patients ≥ 18 years of age at time of ICF signature.
• •3. Pre- or peri-menopausal women being treated with a LHRH analogue for at least 28 days prior to study entry (if shorter, post-menopausal levels of serum estradiol/Follicle-stimulating hormone \[FSH\] must be confirmed analytically), or post-menopausal women as defined by any of the following criteria:
• •1. Age ≥60 years;
• •2. Age \<60 years and cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; and serum estradiol and/or FSH level within the laboratory's reference range for postmenopausal females;
• •3. Documented bilateral oophorectomy.
• •4. Eastern Cooperative Oncology Group (ECOG) performance status lower or equal to 1.
• •5. Life expectancy greater or equal to 6 months.
• •6. Locally advanced or metastatic breast cancer not amenable to treatment with curative intend.
• •7. Histologically confirmed ER-positive and/or PgR-positive (with ≥10% positive stained cells according to National Comprehensive Cancer Network and American Society of Clinical Oncology guidelines) and HER2-negative (0-1+ by immunohistochemistry \[IHC\] or 2+ and negative by in situ hybridization \[ISH\] test) breast cancer based on local testing on the most recent analyzed biopsy.
• •8. Patients with radiological evidence (as per RECIST v.1.1) of disease progression on the immediate prior line of treatment containing a non-steroidal aromatase inhibitor (NSAI) (anastrozole-letrozole). Patients must meet at least one of the following conditions:
• •1. On adjuvant endocrine therapy for ≥ 24 months and relapsing within 12 months after CDK4/6 inhibitor treatment completion following the adjuvant setting.
• •2. Progression to an NSAI in the advanced setting (with or without a CDK4/6 inhibitor) after obtaining clinical benefit (stable disease for ≥ 6 months, CR or PR) Note: Last dose of NSAI (anastrozole or letrozole) of the prior ET must have been received within the 28 days before starting study treatment.
• •9. At least 1 and no more than 3 prior lines of endocrine therapy for ABC, including the treatment received at the time of study entry. ET might have been combined with targeted agents such as everolimus, PI3K inhibitors, CDK4/6 inhibitors, etc.
• •5. Receiving any of following concomitant medications that cannot be discontinued during the study treatment duration (see Section 6.9 and 6.10 for more details):
• •1. Drugs which prolong QT interval, either with a known or a conditional/ possible risk to induce Torsades de Pointes (listed in Appendix 3).
• •2. Coumarin-type anticoagulants (such as warfarin) within one week prior first CB 103 dose. Low molecular weight heparin and direct oral anticoagulants are permitted.
• •6. Current or prior malignancy within 5 years prior to study enrolment, except non-melanoma skin cancer, or carcinoma in situ of the uterine cervix. Patients with other cancers considered to have a low risk of recurrence might be included after approval by the Medical Monitor.
• •7. Radiotherapy or limited-field palliative radiotherapy within 7 days prior to enrolment or patients not having recovered from radiotherapy-related toxicities to baseline or Grade ≤ 1 and/or from whom ≥ 25% of the bone marrow has been previously irradiated.
• •8. Inability to swallow capsules or tablets.
• •9. Impairment of gastrointestinal function or presence of gastrointestinal disease that may significantly alter the absorption of CB-103.
• •10. Impaired cardiac function or clinically significant cardiac disease, including any of the following:
• •1. Clinically significant cardiac disease including congestive heart failure (New York Heart Association \[NYHA\] class III or IV), arrhythmia or conduction abnormality requiring medication, or cardiomyopathy
• •2. Clinically uncontrolled hypertension (systolic blood pressure \> 160 or diastolic blood pressure \>110 mmHg).
• •3. Complete left bundle branch block.
• •4. Right bundle branch block and left anterior hemiblock
• •5. Mandatory use of a cardiac pacemaker.
• •6. Congenital long QT syndrome.
• •7. History or presence of sustained or symptomatic ventricular tachyarrhythmia.
• •8. Presence of atrial fibrillation.
• •9. Clinically significant resting bradycardia (\< 50 bpm).
• •10. Corrected QT interval using Fridericia formula (QTcF) \> 470 ms at the Screening ECG.
• •11. QRS ≥ 110 ms.
• •12. History of symptomatic congestive heart failure.
• •13. Left ventricular ejection fraction (LVEF) \< 50%. History of absolute decrease in LVEF of ≥ 15 absolute percentage points, or ≥ 10 absolute percentage points and crossing from \> lower limits of normal (LLN) to \< LLN on anticancer therapy, even if asymptomatic.
• •14. Angina pectoris ≤ 6 months prior to first CB 103 dose.
• •15. Acute myocardial infarction (MI) ≤ 6 months prior to starting study drug.
• •11. General conditions or other clinically significant diseases, including any one of the following:
• •1. Hemorrhagic, embolic, or thrombotic stroke within 6 months prior to the first CB-103 dose
• •2. Prior allogeneic bone marrow/hematopoietic stem cell transplant
• •3. Prior autologous hematopoietic stem cell transplant for breast cancer (for other indications within ≤ 6 months prior first CB 103 dose.
• •4. Known infection with human immunodeficiency virus (HIV) or hepatitis B or C requiring treatment.
• •5. Any active infection requiring the use of parenteral anti-microbial agents or that is \> Grade 2.
• •6. Non-malignant interstitial lung disease or pneumonitis.
• •7. Dyspnea of any cause requiring supplemental oxygen therapy and dyspnea at rest due to complications of advanced malignancy and co-morbidities.
• •8. Significant traumatic injury or major surgery (i.e., opening of a body cavity, e.g., thoracotomy, laparotomy, laparoscopic organ resection) or major orthopedic procedures (e.g. joint replacement, open reduction and internal fixation) within 14 days prior first CB-103 dose.
• •9. Other concurrent severe and/or uncontrolled medical conditions (e.g. uncontrolled diabetes, active or uncontrolled infection) that could cause unacceptable safety risks or compromise compliance with the protocol.
• •12. Hypersensitivity to CB-103 or any of its excipients.
• •13. Pregnant or breast-feeding patients.