A phase 3, single arm, open-label study evaluating ovarian suppression following 3-month leuprolide acetate for injectable suspension in combination with endocrine therapy in premenopausal subjects with HR+, HER2-negative breast cancer (OVELIA).

Abstract

TPS608 Background: In US clinical practice, GnRH agonists are widely used to suppress ovarian function in pre/perimenopausal patients with breast cancer that is moderate-to high-risk for recurrence. Despite extensive use of leuprolide acetate (LA) for ovarian suppression, regulatory approval for this indication has not been established in the US. Additionally, existing three month formulations may not reliably provide ovarian suppression, as demonstrated by escapes in estradiol (E2). An extended-release LA product with a 3-month dosing period specifically developed for ovarian suppression in patients with breast cancer could fill this unmet need. TOL2506 is a 3-month, extended-release formulation of 30 mg of LA. This combination of active drug and in situ polymeric extended release technology is expected to deliver higher exposure to drug than the currently available 3-month (22.5 mg) formulations of LA marketed for advanced prostate cancer and potentially reduce escapes in E2 over the dosing period. Methods: TOL2506A (OVELIA) is a phase 3, single arm, open-label study evaluating the effectiveness of TOL2506 to suppress ovarian function in premenopausal women with HR+, HER2-negative breast cancer. Approximately 250 subjects will be enrolled, with 30% aged 40 years or younger. Subjects must be premenopausal women, age 18-49, with a diagnosis of Stage I, II, or III HR+, HER2-negative breast cancer (ER > 1% and/or, PR > 1%, HER2-negative per ASCO CAP guidelines), who are candidates for ovarian suppression with endocrine therapy. For subjects receiving chemotherapy, premenopausal status will be determined, and confirmed by central lab hormone testing, prior to initiating chemotherapy. Male subjects with HR+, HER2-negative breast cancer may also be eligible, but will be evaluated for safety analyses only. Eligible subjects will enter the 48 week treatment period in 2 groups: those receiving tamoxifen concurrently with TOL2506 or those who initiate therapy with an aromatase inhibitor (AI; letrozole, anastrozole, or exemestane) beginning 6 weeks after the first administration of TOL2506, if E2 < 20 pg/mL has been achieved. After Week 12, subjects will be allowed to switch from receiving an AI to receiving tamoxifen or from tamoxifen to AI at the Investigator’s discretion. Subjects will receive 4 doses of TOL2506 every 12 weeks over the 48 week study duration. Achievement of ovarian suppression will be defined as ≥ 90% of subjects with luteinizing hormone (LH) levels < 4 IU/L at Week 6. Secondary endpoints include suppression of LH, E2 (< 20 pg/mL for tamoxifen cohort and < 2.72 pg/mL for AI cohort) and absence of menses at weeks 6, 12, 24, 36, and 48. Clinical trial information: NCT04906395.