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

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

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.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 1

Contacts and Locations

Study Locations

• Poland
  • Grudziądz, Poland, 86-300
    • Site 6
  • Kraków, Poland, 30-348
    • Site 4
  • Łódź, Poland, 93-513
    • Site 5
• United States
  • Arizona
    • Gilbert, Arizona, United States, 85234
      • Site 2
  • South Carolina
    • Charleston, South Carolina, United States, 29414
      • Site 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ZN-c5 + abemaciclib combination therapy; 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; ZN-c5 is the study drug.; Drug: Abemaciclib; Abemaciclib (VERZENIO®) is an approved drug.; Other Names: VERZENIO®

What is the study measuring?

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

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): November 12, 2020
• Primary Completion (Actual): October 24, 2022
• Study Completion (Actual): October 24, 2022

Study Registration Dates

• First Submitted: August 11, 2020
• First Submitted That Met QC Criteria: August 11, 2020
• First Posted (Actual): August 14, 2020

Study Record Updates

• Last Update Posted (Actual): November 4, 2022
• Last Update Submitted That Met QC Criteria: November 2, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: Dose escalation; Hormone sensitive; Estrogen receptor; Phase 1 combination; Selective estrogen receptor degrader; Hormone receptor
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: ZN-c5-003

Drug and device information, study documents

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