A Study of ZN-c5 and Abemaciclib in Participants With Breast Cancer

Study Overview
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Brief Summary
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This is a Phase 1b, open-label, multicenter, dose-escalation study to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary efficacy of ZN-c5 administered orally in combination with abemaciclib (VERZENIO®) in participants with advanced estrogen-receptor positive, human epidermal growth factor receptor-2 negative (ER+/HER2-) breast cancer.

Official Title
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A Phase 1b Study of ZN-c5 in Combination With Abemaciclib in Patients With Estrogen-Receptor Positive, Human Epidermal Growth Factor Receptor-2 Negative Advanced Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: ZN-c5
* Drug: Abemaciclib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years of age Women can be peri- or 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 (FSH) level within the laboratory's reference range for postmenopausal females; Documented bilateral oophorectomy; 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 adenocarcinoma of the breast Estrogen receptor positive disease Human Epidermal Growth Factor Receptor 2 negative disease Measurable disease per Response Evaluation Criteria in Solid Tumors v1.1 Exclusion Criteria: Prior therapy within the following windows: Tamoxifen, aromatase inhibitor, fulvestrant, or other anti-cancer endocrine therapy < 14 days; Any investigational drug therapy < 28 days or 5 half-lives (whichever is shorter) Any prior systemic chemotherapy regardless of the stop date, but the subject must have recovered to eligibility levels from prior toxicity Prior treatment with CDK4/6 inhibitors Unexplained symptomatic endometrial disorders (including, but not limited to, endometrial hyperplasia, dysfunctional uterine bleeding, or cysts)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: All participants will receive the same treatment but ZN-c5 will be given at different doses in this dose escalation study.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ZN-c5 + abemaciclib combination therapy<br>Participants will take abemaciclib (150mg) orally twice a day and ZN-c5 (dose escalation) orally once or twice a day to determine the safety, tolerability, and maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D). | Drug: ZN-c5<br>* ZN-c5 is the study drug.<br>Drug: Abemaciclib<br>* Abemaciclib (VERZENIO®) is an approved drug.<br>* Other names: VERZENIO®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and severity of adverse events from ZN-c5 in combination with abemaciclib | Measured by the number of treatment-emergent adverse events and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0 | Through study completion, anticipated to be 21 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine tumor responses to combination treatment | Measured by radiographic responses as defined by revised Response Evaluation Criteria in Solid Tumor (RECIST) v1.1. | Through study completion, anticipated to be 21 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hormone sensitive, Estrogen receptor, Hormone receptor, Dose escalation, Phase 1 combination, Selective estrogen receptor degrader