A Study of ZN-c5 in Subjects With Breast Cancer

NCT03560531 | Completed Phase 1 Results FDA Drug

• 1 other identifier: ZN-c5-001
• Study Type: interventional
• Target: 181
• Locations: 9 countries
• Sites: 38

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®).

Conditions

Breast Cancer

Keywords

Estrogen receptor; Hormone receptor; Selective estrogen receptor degrader; Hormone sensitive; Phase 1 Dose Escalation; Phase 2 Combination; Phase 1 Dose Expansion; Phase 2 Monotherapy

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (13)

• 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 Progression-Free Survival at 8 Months

  8 months

• Monotherapy Only: Percentage of Participants With Progression-Free Survival at 10 Months

  10 months

Study Arms (2)

ZN-c5 monotherapy

EXPERIMENTAL

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 + palbociclib combination therapy

EXPERIMENTAL

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; Drug: Palbociclib

Interventions

ZN-c5 DRUG

ZN-c5 is a study drug

ZN-c5 + palbociclib combination therapy; ZN-c5 monotherapy

Palbociclib DRUG

Palbociclib (IBRANCE®) is an approved drug

Also known as: IBRANCE®

ZN-c5 + palbociclib combination therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• Zeno Alpha Inc.: lead

Study Sites (38)

Site 3

Tucson, Arizona, 85719, United States

Location

Site 5

Los Angeles, California, 91010, United States

Location

Site 48

Bethesda, Maryland, 20817, United States

Location

Site 47

St Louis, Missouri, 63110, United States

Location

Site 7

New York, New York, 10029, United States

Location

Site 2

New York, New York, 10032, United States

Location

Site 50

Charleston, South Carolina, 29414, United States

Location

Site 4

Nashville, Tennessee, 37240, United States

Location

Site 1

Houston, Texas, 77030, United States

Location

Site 8

Houston, Texas, 77030, United States

Location

Site 6

Seattle, Washington, 98195, United States

Location

Site 46

Minsk, 223040, Belarus

Location

Site 45

Vitebsk, 210603, Belarus

Location

Site 10

Banja Luka, 78000, Bosnia and Herzegovina

Location

Site 9

Sarajevo, 71000, Bosnia and Herzegovina

Location

Site 11

Tuzla, 75000, Bosnia and Herzegovina

Location

Site 29

Brno, 65653, Czechia

Location

Site 28

Olomouc, 77900, Czechia

Location

Site 30

Prague, 15006, Czechia

Location

Site 51

Budapest, H-1062, Hungary

Location

Site 35

Kecskemét, H-6000, Hungary

Location

Site 37

Pécs, H-7624, Hungary

Location

Site 17

Kaunas, 50161, Lithuania

Location

Site 16

Vilnius, 08660, Lithuania

Location

Site 40

Nizhny Novgorod, 603089, Russia

Location

Site 52

Omsk, 644013, Russia

Location

Site 41

Pyatigorsk, 357502, Russia

Location

Site 39

Saint Petersburg, 197022, Russia

Location

Site 42

Yekaterinburg, 620036, Russia

Location

Site 18

Belgrade, 11000, Serbia

Location

Site 19

Belgrade, 11080, Serbia

Location

Site 21

Niš, 18000, Serbia

Location

Site 20

Novi Sad, 21204, Serbia

Location

Site 25

Cherkasy, 18009, Ukraine

Location

Site 27

Kharkiv, 61070, Ukraine

Location

Site 24

Kropyvnytskyi, 25006, Ukraine

Location

Site 26

Kryvyi Rih, 50048, Ukraine

Location

Site 23

Kyiv, 03115, Ukraine

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

palbociclib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Limitations and Caveats

In the Phase 2 Monotherapy efficacy analysis, efficacy was to be determined by the clinical benefit rate, combining results with similar treatment groups. The Phase 1 Monotherapy group was combined with Phase 2 Monotherapy group. The Phase 2 Combination part of the study was not initiated.

Results Point of Contact

• Title: Head of Regulatory Affairs
• Organization: Zeno Alpha Inc.

RegLeads@zentalis.com

(858) 263-4333

Study Officials

• Zeno Alpha, Inc.

  Zeno Alpha Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Dose escalation cohorts are planned in monotherapy and combination as well as monotherapy dose expansion, and monotherapy and combination Phase 2.

Study Record Dates

• First Submitted: June 5, 2018
• First Posted: June 18, 2018
• Study Start: November 30, 2018
• Primary Completion: April 26, 2022
• Study Completion: December 22, 2022
• Last Updated: August 9, 2024
• Results First Posted: August 9, 2024

Record last verified: 2024-07

Locations

RU (5); LI (2); US (11); HU (3); SE (4); UA (5); BO (3); BE (2); CZ (3)