A Study of ZN-c5 in Subjects With Breast Cancer

Study Overview
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Brief Summary
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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®).

Official Title
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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

Conditions
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Breast Cancer

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


Participation Criteria
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Eligibility Criteria
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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 FSH level within the laboratory's reference range for postmenopausal females; Documented bilateral oophorectomy; 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 (SD, PR, or CR 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)

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
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Dose escalation cohorts are planned in monotherapy and combination as well as monotherapy dose expansion, and monotherapy and combination Phase 2.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ZN-c5 monotherapy<br>Dose escalation cohorts are planned to determine maximum tolerated dose(MTD) or recommended phase 2 dose (RP2D) of ZN-c5 as well as expansion cohorts and a Phase 2 cohort. | Drug: ZN-c5<br>* ZN-c5 is a study drug<br>|
| Experimental: ZN-c5 + palbociclib combination therapy<br>Dose escalation cohorts are planned to determine maximum tolerated dose(MTD) or recommended phase 2 dose (RP2D) of ZN-c5 in combination with palbociclib as well as a Phase 2 cohort. | Drug: ZN-c5<br>* ZN-c5 is a study drug<br>Drug: Palbociclib<br>* Palbociclib (IBRANCE®) is an approved drug<br>* Other names: IBRANCE®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 1 ESC: Determine a maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) for ZN-c5 as a monotherapy |  | 9 months | 
| Phase 1 ESC: Determine a maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) for ZN-c5 when administered in combination with palbociclib |  | 9 months | 
| Phase 1 EXP: Safety and tolerability of ZN-c5 as a monotherapy as measured by number of treatment-emergent adverse events | Measured by the number of treatment-emergent adverse events | 9 months | 
| Phase 2: Determine preliminary anti-tumor efficacy (Clinical Benefit Rate [CBR]) for ZN-c5 as a monotherapy |  | Through study completion (approximately 2 years) | 
| Phase 2: Determine preliminary anti-tumor efficacy (CBR) for ZN-c5 when administered in combination with palbociclib |  | Through study completion (approximately 2 years) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability of ZN-c5 as a monotherapy as measured by number of treatment-emergent adverse events | Measured by the number of treatment-emergent adverse events | Through study completion (approximately 2 years) | 
| Safety and tolerability of ZN-c5 in combination with palbociclib as measured by number of treatment emergent adverse events | Measured by the number of treatment-emergent adverse events | Through study completion (approximately 2 years) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Estrogen receptor, Hormone receptor, Selective estrogen receptor degrader, Hormone sensitive, Phase 1 Dose Escalation, Phase 2 Combination, Phase 1 Dose Expansion, Phase 2 Monotherapy