A Study of ZN-c5 in Subjects With Breast Cancer
- Registration Number
- NCT03560531
- Lead Sponsor
- Zeno Alpha Inc.
- Brief Summary
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®).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 181
-
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.
-
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)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description ZN-c5 + palbociclib combination therapy Palbociclib 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. ZN-c5 monotherapy ZN-c5 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. ZN-c5 + palbociclib combination therapy ZN-c5 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.
- Primary Outcome Measures
Name Time Method Clinical Benefit Rate (CBR) for ZN-c5 as a Monotherapy 24 weeks CBR is defined as the number of participants who have at least 1 confirmed response of complete response (CR) or partial response (PR) (only if participant has measurable disease), or stable disease (SD) \>= 24 weeks (or non-CR/non-progressive disease (PD) \>=24 weeks for participants with non-measurable disease) prior to any evidence of progression.
Best Overall Response (BOR) for ZN-c5 as a Monotherapy 24 weeks Best overall response was summarized categorically based on the four RECIST categories: CR, PR, SD and PD.
- Secondary Outcome Measures
Name Time Method Monotherapy Only: Percentage of Participants With Progression-Free Survival at 8 Months 8 months PFS is defined as the time (in months) from the date of first dosing until the date of objective PD (as defined by RECIST version 1.1) or death (by any cause in the absence of progression), whichever occurs earlier. Kaplan-Meier estimates at 8 months and their confidence intervals are calculated with the log-log transformation methodology of Kalbfleisch and Prentice.
Monotherapy Only: Percentage of Participants With Overall Survival at 4 Months 4 months OS is defined as the time from the date of enrollment to the date of death from any cause. Kaplan-Meier estimates at 4 months and their confidence intervals are calculated with the log-log transformation methodology of Kalbfleisch and Prentice.
Monotherapy Only: Percentage of Participants With Overall Survival at 8 Months 8 months OS is defined as the time from the date of enrollment to the date of death from any cause. Kaplan-Meier estimates at 8 months and their confidence intervals are calculated with the log-log transformation methodology of Kalbfleisch and Prentice.
Monotherapy Only: Percentage of Participants With Overall Survival at 12 Months 12 months OS is defined as the time from the date of enrollment to the date of death from any cause. Kaplan-Meier estimates at 12 months and their confidence intervals are calculated with the log-log transformation methodology of Kalbfleisch and Prentice.
Monotherapy Only: Percentage of Participants With Progression-Free Survival at 6 Months 6 months PFS is defined as the time (in months) from the date of first dosing until the date of objective PD (as defined by RECIST version 1.1) or death (by any cause in the absence of progression), whichever occurs earlier. Kaplan-Meier estimates at 6 months and their confidence intervals are calculated with the log-log transformation methodology of Kalbfleisch and Prentice.
Monotherapy Only: Percentage of Participants With Progression-Free Survival (PFS) at 2 Months 2 months PFS is defined as the time (in months) from the date of first dosing until the date of objective PD (as defined by RECIST version 1.1) or death (by any cause in the absence of progression), whichever occurs earlier. Kaplan-Meier estimates at 2 months and their confidence intervals are calculated with the log-log transformation methodology of Kalbfleisch and Prentice.
Monotherapy Only: Percentage of Participants With Progression-Free Survival at 4 Months 4 months PFS is defined as the time (in months) from the date of first dosing until the date of objective PD (as defined by RECIST version 1.1) or death (by any cause in the absence of progression), whichever occurs earlier. Kaplan-Meier estimates at 4 months and their confidence intervals are calculated with the log-log transformation methodology of Kalbfleisch and Prentice.
Monotherapy Only: Percentage of Participants With Overall Survival (OS) at 2 Months 2 months OS is defined as the time from the date of enrollment to the date of death from any cause. Kaplan-Meier estimates at 2 months and their confidence intervals are calculated with the log-log transformation methodology of Kalbfleisch and Prentice.
Monotherapy Only: Percentage of Participants With Overall Survival at 6 Months 6 months OS is defined as the time from the date of enrollment to the date of death from any cause. Kaplan-Meier estimates at 6 months and their confidence intervals are calculated with the log-log transformation methodology of Kalbfleisch and Prentice.
Monotherapy Only: Percentage of Participants With Overall Survival at 10 Months 10 months OS is defined as the time from the date of enrollment to the date of death from any cause. Kaplan-Meier estimates at 10 months and their confidence intervals are calculated with the log-log transformation methodology of Kalbfleisch and Prentice.
Objective Response Rate (ORR) for ZN-c5 as a Monotherapy 24 weeks ORR is defined as the number of participants with measurable disease who have at least 1 confirmed response of CR or PR prior to any evidence of progression (as defined by RECIST v1.1).
Monotherapy Only: Percentage of Participants With Progression-Free Survival at 10 Months 10 months PFS is defined as the time (in months) from the date of first dosing until the date of objective PD (as defined by RECIST version 1.1) or death (by any cause in the absence of progression), whichever occurs earlier. Kaplan-Meier estimates at 10 months and their confidence intervals are calculated with the log-log transformation methodology of Kalbfleisch and Prentice.
Monotherapy Only: Percentage of Participants With Progression-Free Survival at 12 Months 12 months PFS is defined as the time (in months) from the date of first dosing until the date of objective PD (as defined by RECIST version 1.1) or death (by any cause in the absence of progression), whichever occurs earlier. Kaplan-Meier estimates at 12 months and their confidence intervals are calculated with the log-log transformation methodology of Kalbfleisch and Prentice.
Trial Locations
- Locations (38)
Site 30
🇨🇿Praha 5, Czechia
Site 3
🇺🇸Tucson, Arizona, United States
Site 5
🇺🇸Los Angeles, California, United States
Site 47
🇺🇸Saint Louis, Missouri, United States
Site 7
🇺🇸New York, New York, United States
Site 50
🇺🇸Charleston, South Carolina, United States
Site 2
🇺🇸New York, New York, United States
Site 8
🇺🇸Houston, Texas, United States
Site 46
🇧🇾Minsk, Belarus
Site 45
🇧🇾Vitebsk, Belarus
Site 10
🇧🇦Banja Luka, Bosnia and Herzegovina
Site 9
🇧🇦Sarajevo, Bosnia and Herzegovina
Site 11
🇧🇦Tuzla, Bosnia and Herzegovina
Site 28
🇨🇿Olomouc, Czechia
Site 29
🇨🇿Brno, Czechia
Site 37
🇭🇺Pécs, Hungary
Site 17
🇱🇹Kaunas, Lithuania
Site 16
🇱🇹Vilnius, Lithuania
Site 40
🇷🇺Nizhniy Novgorod, Russian Federation
Site 42
🇷🇺Ekaterinburg, Russian Federation
Site 41
🇷🇺Pyatigorsk, Russian Federation
Site 52
🇷🇺Omsk, Russian Federation
Site 18
🇷🇸Belgrade, Serbia
Site 19
🇷🇸Belgrade, Serbia
Site 20
🇷🇸Novi Sad, Serbia
Site 27
🇺🇦Kharkiv, Ukraine
Site 25
🇺🇦Cherkasy, Ukraine
Site 23
🇺🇦Kyiv, Ukraine
Site 26
🇺🇦Kryvyi Rih, Ukraine
Site 1
🇺🇸Houston, Texas, United States
Site 6
🇺🇸Seattle, Washington, United States
Site 4
🇺🇸Nashville, Tennessee, United States
Site 24
🇺🇦Kropyvnytskyi, Ukraine
Site 21
🇷🇸Niš, Serbia
Site 39
🇷🇺Saint Petersburg, Russian Federation
Site 51
🇭🇺Budapest, Hungary
Site 35
🇭🇺Kecskemét, Hungary
Site 48
🇺🇸Bethesda, Maryland, United States