A Study of ZN-c5 in Subjects With Breast Cancer

A Phase 1/2 Open Label, Multicenter Study to Assess the Safety, Tolerability, Pharmacokinetics, and Anti-Tumor Activity of ZN-c5 Alone and in Combination With Palbociclib in Subjects With Estrogen-Receptor Positive, Human Epidermal Growth Factor Receptor-2 Negative Advanced Breast Cancer

This is a Phase 1/2, open-label, multicenter, dose-escalation and expansion study to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of ZN-c5 administered orally in subjects with advanced estrogen receptor positive, human epidermal growth factor receptor 2 negative (ER+/HER2-) breast cancer. ZN-c5 will be evaluated both as monotherapy and in combination with palbociclib (IBRANCE®).

Inclusion Criteria:

• Age ≥ 18 years of age

  • Women can be postmenopausal, as defined by at least one of the following:
  • Age ≥ 60 years;
  • 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 follicle-stimulating hormone level within the laboratory's reference range for postmenopausal females;
  • Documented bilateral oophorectomy; or can be peri- or premenopausal, however, they must receive a gonadotrophin-releasing hormone agonist beginning at least 4 weeks prior to the first dose of study medication.

• Histologically or cytologically confirmed diagnosis of advanced (metastatic or locoregionally recurrent) adenocarcinoma of the breast, not amenable to any potential curative intervention

• Estrogen Receptor (ER) positive disease

• Human Epidermal Growth Factor Receptor 2 (HER2) negative disease

• Documented prior response to endocrine therapy for metastatic disease (stable disease, partial response, or complete response by RECIST v1.1 criteria) lasting > 6 months

• Evaluable or measurable disease by RECIST v1.1. Tumor lesions previously irradiated or subjected to other locoregional therapy will only be deemed measurable if progression at the treated site after completion of therapy is clearly documented.

Exclusion Criteria:

• Prior anticancer or investigational drugs for the treatment of ER+/HER2 negative advanced breast cancer within the following windows:

  • Tamoxifen, aromatase inhibitor, fulvestrant, or other anti-cancer endocrine therapy < 14 days before first dose of study treatment
  • Any chemotherapy < 28 days before first dose of study, except for Phase 2 monotherapy which requires no prior chemotherapy treatment.
  • Any investigational drug therapy < 28 days or 5 half-lives (whichever is shorter) prior to first dose of study treatment

• Unexplained symptomatic endometrial disorders (including, but not limited to endometrial hyperplasia, dysfunctional uterine bleeding, or cysts)