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
Overview
- Phase
- Phase 1
- Intervention
- Palbociclib
- Conditions
- Breast Cancer
- Sponsor
- Zeno Alpha Inc.
- Enrollment
- 181
- Locations
- 38
- Primary Endpoint
- Clinical Benefit Rate (CBR) for ZN-c5 as a Monotherapy
- Status
- Completed
- Last Updated
- last year
Overview
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®).
Investigators
Eligibility Criteria
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.
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)
Arms & Interventions
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.
Intervention: Palbociclib
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.
Intervention: ZN-c5
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.
Intervention: ZN-c5
Outcomes
Primary Outcomes
Clinical Benefit Rate (CBR) for ZN-c5 as a Monotherapy
Time Frame: 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
Time Frame: 24 weeks
Best overall response was summarized categorically based on the four RECIST categories: CR, PR, SD and PD.
Secondary Outcomes
- Monotherapy Only: Percentage of Participants With Progression-Free Survival at 8 Months(8 months)
- Monotherapy Only: Percentage of Participants With Overall Survival at 4 Months(4 months)
- Monotherapy Only: Percentage of Participants With Overall Survival at 8 Months(8 months)
- Monotherapy Only: Percentage of Participants With Overall Survival at 12 Months(12 months)
- Monotherapy Only: Percentage of Participants With Progression-Free Survival (PFS) at 2 Months(2 months)
- Monotherapy Only: Percentage of Participants With Progression-Free Survival at 4 Months(4 months)
- Monotherapy Only: Percentage of Participants With Progression-Free Survival at 6 Months(6 months)
- Monotherapy Only: Percentage of Participants With Overall Survival (OS) at 2 Months(2 months)
- Monotherapy Only: Percentage of Participants With Overall Survival at 6 Months(6 months)
- Monotherapy Only: Percentage of Participants With Overall Survival at 10 Months(10 months)
- Objective Response Rate (ORR) for ZN-c5 as a Monotherapy(24 weeks)
- Monotherapy Only: Percentage of Participants With Progression-Free Survival at 10 Months(10 months)
- Monotherapy Only: Percentage of Participants With Progression-Free Survival at 12 Months(12 months)