Ovarian Suppression Evaluating Subcutaneous Leuprolide Acetate in Breast Cancer

Prior treatment

• Prior use of tamoxifen, other SERMs (eg, raloxifene) or antagonists (eg, fulvestrant), aromatase inhibitor, mammalian target of rapamycin (mTOR) inhibitors, or hormone replacement therapy within 3 months before breast cancer diagnosis
• Concomitant use of anticancer mediations other than those specified for use by the protocol
• Prior neoadjuvant or adjuvant endocrine therapy since diagnosis of breast cancer
• Prior (within 6 months prior to Day 1) or current use of drugs known to increase bone mineral density (ie, bisphosphonates, denosumab, teriparatide, abaloparatide, romosozumab) or use of supplements known to increase bone mineral density (ie, calcitonin, fluoride, strontium) within 28 days prior to Day 1
• Low trauma fracture(s) occurring within 12 months prior to subject's first visit (defined as a fracture that results from a fall from a standing height or less, excluding fingers, toes, face and skull)
• Already receiving and/or previously received GnRH analogs within 1 year before breast cancer diagnosis
• Use of medications that may impact subject safety and/or affect the PK of the drug and hormonal assessments including but not limited to:
  • Oral or transdermal hormonal therapy within 30 days prior to subject's first visit
  • Estrogen, progesterone, or androgens within 30 days prior to subject's first visit
  • Hormonal contraceptives within 30 days prior to subject's first visit
  • Medications known to result in clinically important decreases in bone mass taken within 6 months prior to subject's first visit
• Exposure to any investigational agent within 30 days prior to the first dose of TOL2506
  • See contact information to obtain inclusion/exclusion criteria for males

Other illness

• History of treatment for osteopenia/osteoporosis or baseline bone mineral density Z-score ≤ -2.0
• Conditions that preclude bone mineral density measurement (lumbar spine/bilateral hip surgery with hardware in place, abdominal clips, umbilical ring \[not willing to remove\] or weight that exceeds the DEXA machine limitation)
• Psychiatric, addictive, or other disorders that would preclude study compliance
• Known hypersensitivity, idiosyncratic, or allergic reactions to GnRH, GnRH agonist/analogs or to any of the components of the IP

Lab values

• Unacceptable hepatic function as determined by any of the following:
  • Alanine aminotransferase (ALT) ≥ 2X upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) ≥ 2X ULN
  • Bilirubin ≥ 2X ULN
  • Alkaline phosphatase ≥ 2X ULN
  • Severe hepatic impairment (Child-Pugh Class C)
• Unacceptable renal function as determined by any of the following:
  • Creatinine ≥ 3X ULN
  • Creatinine clearance ≤ 30 mL/minute
  • Creatinine clearance ≤ 60 mL/minute in subjects with bone density 1.5 standard deviations below the young adult normal mean
• History of significantly abnormal ECG or screening 12-lead ECG demonstrating any of the following:
  • HR \> 100 BPM
  • QRS \> 120 msec
  • QTc \> 450 msec
  • PR \> 220 msec
• Prior (within 28 days prior to Day 1) and/or concomitant use of medications known to prolong the QT/QTc interval
• Any other medical condition or serious illness, presence of a second malignancy under current treatment or follow-up, or the presence of clinically significant findings on the physical exam, laboratory testing, medical history (including conditions that may be associated with low bone mass), that in the opinion of the Investigator may interfere with trial conduct, subject safety, or interpretation of study results
• Is of childbearing potential with a positive serum pregnancy test at Screening or urine pregnancy test at Day 1

Other

• Body mass index (BMI) \< 18.00 kg/m2 or \> 35.00 kg/m2
• Breastfeeding
• Life expectancy \< 12 months
• Eastern Cooperative Oncology Group (ECOG) performance status ≥ 3
• Sexually active with a male partner and not willing to use non-hormonal contraceptive methods throughout the study

• Female
• Able to understand the investigational nature of this study and provide written informed consent prior to the participation in the trial
• Age 18 to 49, inclusive
• Diagnosis of Stage I, II, or III HR+, HER2-negative breast cancer (ER\>1% and/or, PR\>1%, HER2-negative per ASCO CAP guidelines)
• Is a candidate for endocrine therapy + ovarian suppression LH \> 4 IU/L within 28 days prior to Day 1
• Is premenopausal as defined by:
  • E2 \> 30 pg/mL
  • follicle stimulating hormone (FSH) \< 40 IU/L
  • regular menses (eg, menstrual cycle length of 21 to 35 days) Note: premenopausal status must be determined before neo/adjuvant chemotherapy in patients for which it is planned or prior to Day 1 in patients who did not have prior chemotherapy. If premenopausal status was not determined prior to chemotherapy, E2 and FSH must meet the above criteria when measured 2 weeks or more after the end of the final cycle of chemotherapy.