A Study of ZN-c5 in Subjects With Breast Cancer

Inclusion Criteria:

- Age ≥ 18 years of age who are 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
FSH level within the laboratory's reference range for postmenopausal females;

- Documented bilateral oophorectomy;

- Medically confirmed ovarian failure.

- 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

- Radiographic documentation of disease progression on the last (most recent) treatment
administered prior to enrolling in the study.

- Documented prior response to endocrine therapy for metastatic disease (SD, PR, or CR
by RECIST v1.1 criteria) lasting > 6 months

- Measurable disease meeting the criteria specified 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.

(Note: subjects with bone-only metastatic cancer may be enrolled in the dose escalation
portion of the study but must have a lytic or mixed lytic-blastic lesion that can be
accurately assessed by CT or MRI.)

Exclusion Criteria:

- Subjects who have received only neoadjuvant or adjuvant therapy for breast
adenocarcinoma

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

- Tamoxifen, aromatase inhibitor, or other anti-cancer endocrine therapy < 14 days
before first dose of study treatment

- Any chemotherapy < 28 days before first dose of study

- Any investigational drug therapy < 28 days or 3 half-lives (whichever is longer)
prior to first dose of study treatment

- Combination Therapy: Any prior treatment with any CDK4/6 inhibitor (combination
cohorts only)

- Any prior treatment with immunotherapy (e.g. ipilimumab, nivolumab, pembrolizumab,
atezolizumab)

- Patients with bone-only disease (Dose Expansion cohorts only) Note: Patients with
bone-only disease may be enrolled in the Dose Escalation portion of the study, but
must have a lytic or mixed lytic-blastic lesion that can be accurately assessed by CT
or MRI

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