Ovarian Suppression Evaluating Subcutaneous Leuprolide Acetate in Breast Cancer

Inclusion Criteria:

Female

1. Able to understand the investigational nature of this study and provide writteninformed consent prior to the participation in the trial

2. Age 18 to 49, inclusive

3. Diagnosis of Stage I, II, or III HR+, HER2-negative breast cancer (ER>1% and/or,PR>1%, HER2-negative per ASCO CAP guidelines)

4. Is a candidate for endocrine therapy + ovarian suppression LH > 4 IU/L within 28days prior to Day 1

5. 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 inpatients for which it is planned or prior to Day 1 in patients who did not haveprior chemotherapy. If premenopausal status was not determined prior tochemotherapy, E2 and FSH must meet the above criteria when measured 2 weeks ormore after the end of the final cycle of chemotherapy.

Exclusion Criteria:

1. Body mass index (BMI) < 18.00 kg/m2 or > 35.00 kg/m2

2. Breastfeeding

3. Life expectancy < 12 months

4. Eastern Cooperative Oncology Group (ECOG) performance status ≥ 3

5. Unacceptable hepatic function as determined by any of the following:

6. Alanine aminotransferase (ALT) ≥ 2X upper limit of normal (ULN)

7. Aspartate aminotransferase (AST) ≥ 2X ULN

8. Bilirubin ≥ 2X ULN

9. Alkaline phosphatase ≥ 2X ULN

10. Severe hepatic impairment (Child-Pugh Class C)

11. Unacceptable renal function as determined by any of the following:

12. Creatinine ≥ 3X ULN

13. Creatinine clearance ≤ 30 mL/minute

14. Creatinine clearance ≤ 60 mL/minute in subjects with bone density 1.5 standarddeviations below the young adult normal mean

15. History of significantly abnormal ECG or screening 12-lead ECG demonstrating any ofthe following:

16. HR > 100 BPM

17. QRS > 120 msec

18. QTc > 450 msec

19. PR > 220 msec

20. Prior (within 28 days prior to Day 1) and/or concomitant use of medications known toprolong the QT/QTc interval

21. 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

22. Concomitant use of anticancer mediations other than those specified for use by theprotocol

23. Prior neoadjuvant or adjuvant endocrine therapy since diagnosis of breast cancer

24. History of treatment for osteopenia/osteoporosis or baseline bone mineral densityZ-score ≤ -2.0

25. Prior (within 6 months prior to Day 1) or current use of drugs known to increasebone 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

26. 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)

27. Conditions that preclude bone mineral density measurement (lumbar spine/bilateralhip surgery with hardware in place, abdominal clips, umbilical ring [not willing toremove] or weight that exceeds the DEXA machine limitation)

28. Any other medical condition or serious illness, presence of a second malignancyunder current treatment or follow-up, or the presence of clinically significantfindings on the physical exam, laboratory testing, medical history (includingconditions that may be associated with low bone mass), that in the opinion of theInvestigator may interfere with trial conduct, subject safety, or interpretation ofstudy results

29. Already receiving and/or previously received GnRH analogs within 1 year beforebreast cancer diagnosis

30. Psychiatric, addictive, or other disorders that would preclude study compliance

31. Use of medications that may impact subject safety and/or affect the PK of the drugand hormonal assessments including but not limited to:

32. Oral or transdermal hormonal therapy within 30 days prior to subject's firstvisit

33. Estrogen, progesterone, or androgens within 30 days prior to subject's firstvisit

34. Hormonal contraceptives within 30 days prior to subject's first visit

35. Medications known to result in clinically important decreases in bone masstaken within 6 months prior to subject's first visit

36. Known hypersensitivity, idiosyncratic, or allergic reactions to GnRH, GnRHagonist/analogs or to any of the components of the IP

37. Sexually active with a male partner and not willing to use non-hormonalcontraceptive methods throughout the study

38. Is of childbearing potential with a positive serum pregnancy test at Screening orurine pregnancy test at Day 1

39. Exposure to any investigational agent within 30 days prior to the first dose ofTOL2506

See contact information to obtain inclusion/exclusion criteria for males