Estrogen-receptor positive, human epidermal growth factor receptor-2 negative advanced breast cancer MedDRA version: 21.1 Level: LLT Classification code 10072737 Term: Advanced breast cancer System Organ Class: 100000004864
Conditions
Interventions
Product Code: ZN-c5
Pharmaceutical Form: Capsule
INN or Proposed INN: pending
CAS Number: 2136606-87-4
Current Sponsor code: ZN-c5
Other descriptive name: KP-868
Concentration unit: mg milligram(s)
Co
Sponsors
Zeno Alpha, Inc.,
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Male or female 2) Age = 18 years 3) Menopausal Status [Female subjects]: Postmenopausal, as defined by at least one of the following a) Age = 60 years; b) Age 1% positive stained cells based on medical record, archival tumor biopsy, or de novo tumor biopsy b) [Monotherapy Expansion/Monotherapy Phase 2/Combination Phase 2 Cohorts]: > 10% positive stained cells 6) Human Epidermal Growth Factor Receptor 2 (HER2) negative disease as documented by a local laboratory a) [Monotherapy Escalation and Combination Dose Escalation Cohorts]: Documentation by medical record or archival tumor tissue allowed b) [Monotherapy Expansion/Monotherapy Phase 2/Combination Phase 2 Cohorts]: Based on analysis of archival tumor biopsy or de novo biopsy with HER2-negativity defined as: 1) Immunohistochemistry score 0/1+ or 2) Negative by in situ hybridization (FISH/CISH/SISH) defined as a HER2/CEP17 ratio 6 months or disease recurrence after at least 24 months of adjuvant endocrine treatment. (not required for treatment naïve patients) 10) Prior Chemotherapy: a) [Monotherapy Dose Escalation Cohort]: Up to 2 prior lines of chemotherapy for the treatment of advanced breast cancer b) [Monotherapy Phase 2]: No prior chemotherapeutic regimens for the treatment of advanced breast cancer c) [Monotherapy Expansion, Combination Dose Escalation and Combination Phase 2 Cohorts]: Up to 1 prior line of chemotherapy for the treatment of advanced breast cancer In counting lines of treatment for advanced/metastatic disease, any change in regimen due to PD or toxicity will be counted as a separate line of treatment. 11) Prior treatment with a CDK4/6 i
Exclusion criteria
Exclusion criteria: 1) Any of the following within the specified window prior to the first dose of study drug: a) Tamoxifen, AI, fulvestrant or other anti-cancer endocrine therapy 25% of bone marrow 4) Brain metastases that require immediate treatment or are clinically or radiologically unstable (i.e., have been stable for Grade 1 13) Myocardial infarction, symptomatic congestive heart failure (NYHA > Class II), unstable angina, or serious uncontrolled cardiac arrhythmia within the last 6 months 14) QTc interval > 480 msec (based on the mean value of the triplicate ECGs), family or personal history of long or short QT syndrome, Brugada syndrome or history of Torsade de Pointes 15) Concurrent use of food or drugs known to be moderate or strong CYP3A or CYP2C9 inducers and moderate or strong CYP3A4 or CYP2C9 inhibitors. In addition, for moderate or strong CYP3A or CYP2C9 inducers, there should be a wash-out of 14 days (or 5 half-lives, whichever is shorter) before the first administration of study drug 16) Any clinically significant disorder, condition, or disease that, in the opinion of the Investigator or Medical Monitor would pose a risk to subject safety.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Phase 1 • Monotherapy Dose Escalation: Determine a maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D) for ZN-c5 as a monotherapy • Monotherapy Expansion: Investigate the safety and tolerability of ZN-c5 as a monotherapy in subjects with Estrogen Receptor (ER) positive, Human Epidermal Growth Factor Receptor-2 (HER2) negative advanced breast cancer • Combination Dose Escalation: Determine an MTD or RP2D for ZN-c5 when administered in combination with palbociclib Phase 2 • Monotherapy Phase 2: Determine preliminary anti-tumor efficacy (Clinical Benefit Rate [CBR]) for ZN-c5 as a monotherapy • Combination Phase 2: Determine preliminary anti-tumor efficacy (Clinical Benefit Rate [CBR]) for ZN-c5 when administered in combination with palbociclib ;Secondary Objective: • Monotherapy Dose Escalation and Monotherapy Phase 2: Investigate the safety and tolerability of ZN-c5 as a monotherapy in subjects with ER positive, HER2 negative advanced breast cancer • Combination Dose Escalation and Combination Phase 2: Investigate the safety and tolerability of ZN-c5 in combination with palbociclib in subjects with ER positive, HER2 negative advanced breast cancer • Monotherapy Expansion Phase 1: Investigate the preliminary antitumor efficacy (CBR) for ZN-c5 as a monotherapy • All Cohorts: Assess preliminary efficacy of ZN-c5 alone and in combination with palbociclib by Objective Response Rate (ORR), CBR, Duration of Response (DOR), Progression-Free Survival (PFS) and Overall Survival (OS) using Response Evaluation Criteria in Solid Tumors (RECIST v.1.1) as assessed by investigators • Monotherapy Dose Escalation and Monotherapy Expansion Phase 1 and Monotherapy Phase 2: Characterize the pharmacokinetics (PK) of ZN-c5;Primary end point(s): Monotherapy Dose Escalation and Combination Dose Escalation: Observed Dose Limiting Toxicities • Monotherapy Expansion: Safety and tolerability as measured by incidence of treatment-emergent adverse events (TEAEs) and lab | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • All Cohorts: Safety and tolerability as measured by incidence of treatment-emergent AEs and lab abnormalities • Monotherapy Expansion: CBR (CR [+ PR] + SD = 24 weeks). PR will only be included for patients with measurable disease. • All Cohorts: Tumor response including ORR, DOR, CBR, PFS using Response Evaluation Criteria in Solid Tumors (RECIST v.1.1) as assessed by Investigators, and OS • All Cohorts: ZN-c5 (and its potential metabolites as applicable) and palbociclib (if applicable) plasma pharmacokinetic (PK) parameters (including Cmax, Tmax, AUClast, t½ and Ctau, as applicable) ;Timepoint(s) of evaluation of this end point: Following the determination of the MTD/RP2D for ZN-c5 in combination with palbociclib, additional subjects will be enrolled to further assess the safety, tolerability, and preliminary efficacy of ZN-c5 in combination with palbociclib. Patients are evaluable for assessment of anti-tumor efficacy (based on CBR) if they were dosed and had at least 1 post baseline disease/tumor assessment. CBR as measured using RECIST v.1.1 will be assessed to provide a preliminary, anti-tumor activity evaluation. | — |
Countries
Belarus, Belgium, Bosnia and Herzegovina, Bulgaria, Croatia, Czechia, Czech Republic, Georgia, Hungary, Lebanon, Lithuania, Moldova, Republic of, Russian Federation, Serbia, Turkey, Ukraine, United Kingdom, United States
Contacts
Public ContactVP Regulatory & Quality
Zeno Alpha, Inc.,
Outcome results
None listed