Safety Extension Study for Subjects With HR+, HER2- Breast Cancer for Subjects Who Have Completed the OVELIA Study

Open-label, Safety Extension Study for Subjects With HR+, HER2-Negative Breast Cancer Who Have Completed the OVarian Suppression Evaluating Subcutaneous LeuprolIde Acetate in Breast Cancer OVELIA Study

TOL2506A (OVELIA) is a Phase 3, single arm, open-label study evaluating the effectiveness of TOL2506 in suppressing ovarian function in premenopausal women with HR+, HER2-negative breast cancer and men with HR+ breast cancer. The TOL2506A-EXT study described here is a safety extension study to assess and collect long-term data on the ongoing safety and tolerability of TOL2506 in combination with tamoxifen or an AI for up to 4 years.

Inclusion Criteria:

Females:

1. Completed Visit 9, Week 48 visit of TOL2506A study and is a candidate for continued endocrine therapy + ovarian suppression
2. Able to understand the investigational nature of this study and provide written informed consent prior to the participation in the trial
3. Age 18 to 51 inclusive

Exclusion Criteria:

• Females:

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

  2. Life expectancy < 12 months

  3. ECOG performance status ≥ 3

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

     1. Alanine aminotransferase (ALT) ≥ 2X upper limit of normal (ULN)
     2. Aspartate aminotransferase (AST) ≥ 2X ULN
     3. Bilirubin ≥ 2X ULN
     4. Alkaline phosphatase ≥ 2X ULN
     5. Severe hepatic impairment (Child-Pugh Class C)

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

     1. Creatinine ≥ 3X ULN
     2. Creatinine clearance ≤ 30 mL/minute
     3. Creatinine clearance ≤ 60 mL/minute in subjects with bone density 1.5 standard deviations below the young adult normal mean

  6. Screening 12-lead ECG demonstrating any of the following:

     1. Heart rate > 100 beats per minute (BPM)
     2. QRS > 120 msec
     3. Corrected QT (QTc) > 450 msec
     4. PR > 220 msec

  7. Use of any new medications known to prolong the QT/QTc interval

  8. Any new medical condition or psychiatric, addictive or other disorder that, in the opinion of the Investigator, may interfere with trial conduct or result in the subject being ineligible to continue treatment with TOL2506

  9. Concomitant use of medications that may impact subject safety including but not limited to:

     1. Oral or transdermal hormonal therapy
     2. Estrogen, progesterone, or androgens
     3. Hormonal contraceptives

  10. Change in tolerability to TOL2506 that precludes continued treatment

  11. Sexually active with a male partner and not willing to use at least 2 non-hormonal contraceptive methods throughout the study

  12. Is of childbearing potential with a positive urine pregnancy test at Screening

Males:

Inclusion Criteria:

1. Completed Visit 9, Week 48 visit of TOL2506A study and is a candidate for continued endocrine + GnRH agonist therapy
2. Able to understand the investigational nature of this study and provide written informed consent prior to participation in the trial

Males:

Exclusion Criteria:

1. BMI < 18.00 kg/m2

2. Life expectancy < 12 months

3. ECOG performance status ≥ 3

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

   1. ALT ≥ 2X ULN
   2. AST ≥ 2X ULN
   3. Bilirubin ≥ 2X ULN
   4. Alkaline phosphatase ≥ 2X ULN
   5. Severe hepatic impairment (Child-Pugh Class C)

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

   1. Creatinine ≥ 3X ULN
   2. Creatinine clearance ≤ 30 mL/minute
   3. Creatinine clearance ≤ 60 mL/minute in subjects with bone density 1.5 standard deviations below the young adult normal mean

6. Screening 12-lead ECG demonstrating any of the following:

   1. HR > 100 BPM
   2. QRS > 120 msec
   3. QTc > 450 msec
   4. PR > 220 msec

7. Use of any new medications known to prolong the QT/QTc interval

8. Any new medical condition or psychiatric, addictive or other disorder that, in the opinion of the Investigator, may interfere with trial conduct or result in the subject being ineligible to continue treatment with TOL2506

9. Concomitant use of medications that may impact subject safety including but not limited to oral or transdermal hormonal therapy

10. Change in tolerability to TOL2506 that precludes continued treatment.