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®).

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: ZN-c5; Drug: Palbociclib

• Study Type: Interventional
• Enrollment (Actual): 181
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Belarus
  • Minsk, Belarus, 223040
    • Site 46
  • Vitebsk, Belarus, 210603
    • Site 45
• Bosnia and Herzegovina
  • Banja Luka, Bosnia and Herzegovina, 78000
    • Site 10
  • Sarajevo, Bosnia and Herzegovina, 71000
    • Site 9
  • Tuzla, Bosnia and Herzegovina, 75000
    • Site 11
• Czechia
  • Brno, Czechia, 65653
    • Site 29
  • Olomouc, Czechia, 77900
    • Site 28
  • Praha 5, Czechia, 15006
    • Site 30
• Hungary
  • Budapest, Hungary, H-1062
    • Site 51
  • Kecskemét, Hungary, H-6000
    • Site 35
  • Pécs, Hungary, H-7624
    • Site 37
• Lithuania
  • Kaunas, Lithuania, 50161
    • Site 17
  • Vilnius, Lithuania, 08660
    • Site 16
• Russian Federation
  • Ekaterinburg, Russian Federation, 620036
    • Site 42
  • Nizhniy Novgorod, Russian Federation, 603089
    • Site 40
  • Omsk, Russian Federation, 644013
    • Site 52
  • Pyatigorsk, Russian Federation, 357502
    • Site 41
  • Saint Petersburg, Russian Federation, 197022
    • Site 39
• Serbia
  • Belgrade, Serbia, 11000
    • Site 18
  • Belgrade, Serbia, 11080
    • Site 19
  • Niš, Serbia, 18000
    • Site 21
  • Novi Sad, Serbia, 21204
    • Site 20
• Ukraine
  • Cherkasy, Ukraine, 18009
    • Site 25
  • Kharkiv, Ukraine, 61070
    • Site 27
  • Kropyvnytskyi, Ukraine, 25006
    • Site 24
  • Kryvyi Rih, Ukraine, 50048
    • Site 26
  • Kyiv, Ukraine, 03115
    • Site 23
• United States
  • Arizona
    • Tucson, Arizona, United States, 85719
      • Site 3
  • California
    • Los Angeles, California, United States, 91010
      • Site 5
  • Maryland
    • Bethesda, Maryland, United States, 20817
      • Site 48
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Site 47
  • New York
    • New York, New York, United States, 10029
      • Site 7
    • New York, New York, United States, 10032
      • Site 2
  • South Carolina
    • Charleston, South Carolina, United States, 29414
      • Site 50
  • Tennessee
    • Nashville, Tennessee, United States, 37240
      • Site 4
  • Texas
    • Houston, Texas, United States, 77030
      • Site 1
    • Houston, Texas, United States, 77030
      • Site 8
  • Washington
    • Seattle, Washington, United States, 98195
      • Site 6

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ZN-c5 monotherapy; 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; ZN-c5 is a study drug
Experimental: ZN-c5 + palbociclib combination therapy; 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; ZN-c5 is a study drug; Drug: Palbociclib; Palbociclib (IBRANCE®) is an approved drug; Other Names: IBRANCE®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Benefit Rate (CBR) for ZN-c5 as a Monotherapy	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.	24 weeks
Best Overall Response (BOR) for ZN-c5 as a Monotherapy	Best overall response was summarized categorically based on the four RECIST categories: CR, PR, SD and PD.	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Monotherapy Only: Percentage of Participants With Progression-Free Survival (PFS) at 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.	2 months
Monotherapy Only: Percentage of Participants With Progression-Free Survival at 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.	4 months
Monotherapy Only: Percentage of Participants With Progression-Free Survival at 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.	6 months
Monotherapy Only: Percentage of Participants With Progression-Free Survival at 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.	8 months
Monotherapy Only: Percentage of Participants With Progression-Free Survival at 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.	10 months
Monotherapy Only: Percentage of Participants With Progression-Free Survival at 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.	12 months
Monotherapy Only: Percentage of Participants With Overall Survival (OS) at 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.	2 months
Monotherapy Only: Percentage of Participants With Overall Survival at 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.	4 months
Monotherapy Only: Percentage of Participants With Overall Survival at 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.	6 months
Monotherapy Only: Percentage of Participants With Overall Survival at 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.	8 months
Monotherapy Only: Percentage of Participants With Overall Survival at 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.	10 months
Monotherapy Only: Percentage of Participants With Overall Survival at 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.	12 months
Objective Response Rate (ORR) for ZN-c5 as a Monotherapy	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).	24 weeks

Collaborators and Investigators

• Sponsor: Zeno Alpha Inc.
• Investigators: Study Director: Zeno Alpha, Inc., Zeno Alpha Inc.

Study record dates

Study Major Dates

• Study Start (Actual): November 30, 2018
• Primary Completion (Actual): April 26, 2022
• Study Completion (Actual): December 22, 2022

Study Registration Dates

• First Submitted: June 5, 2018
• First Submitted That Met QC Criteria: June 15, 2018
• First Posted (Actual): June 18, 2018

Study Record Updates

• Last Update Posted (Actual): August 9, 2024
• Last Update Submitted That Met QC Criteria: July 10, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: Hormone sensitive; Estrogen receptor; Selective estrogen receptor degrader; Hormone receptor; Phase 1 Dose Escalation; Phase 2 Combination; Phase 1 Dose Expansion; Phase 2 Monotherapy
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Palbociclib
• Other Study ID Numbers: ZN-c5-001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No