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    Summary
    EudraCT Number:2018-001364-27
    Sponsor's Protocol Code Number:ZN-c5-001
    National Competent Authority:Bulgarian Drug Agency
    Clinical Trial Type:EEA CTA
    Trial Status:Prematurely Ended
    Date on which this record was first entered in the EudraCT database:2020-08-05
    Trial results View results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedBulgarian Drug Agency
    A.2EudraCT number2018-001364-27
    A.3Full title of the trial
    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
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Clinical trial for patients with advanced breast cancer
    A.4.1Sponsor's protocol code numberZN-c5-001
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorZeno Alpha, Inc.,
    B.1.3.4CountryUnited States
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportZeno Alpha, Inc.,
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationZeno Alpha, Inc.,
    B.5.2Functional name of contact pointVP Regulatory & Quality
    B.5.3 Address:
    B.5.3.1Street Address530 7th Ave, Suite 2201
    B.5.3.2Town/ cityNew York
    B.5.3.3Post code10018
    B.5.3.4CountryUnited States
    B.5.4Telephone number+1609619 9909
    B.5.6E-mailmrao@zentalis.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.2Product code ZN-c5
    D.3.4Pharmaceutical form Capsule
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNpending
    D.3.9.1CAS number 2136606-87-4
    D.3.9.2Current sponsor codeZN-c5
    D.3.9.3Other descriptive nameKP-868
    D.3.9.4EV Substance CodeSUB196425
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number25
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 2
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.2Product code ZN-c5
    D.3.4Pharmaceutical form Capsule
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNpending
    D.3.9.1CAS number 2136606-87-4
    D.3.9.2Current sponsor codeZN-c5
    D.3.9.3Other descriptive nameKP-868
    D.3.9.4EV Substance CodeSUB196425
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number100
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 3
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name IBRANCE
    D.2.1.1.2Name of the Marketing Authorisation holderPfizer Europe MA EEIG
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameIbrance
    D.3.4Pharmaceutical form Capsule, hard
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNPALBOCICLIB
    D.3.9.1CAS number 571190-30-2
    D.3.9.4EV Substance CodeSUB177204
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number125
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 4
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name IBRANCE
    D.2.1.1.2Name of the Marketing Authorisation holderPfizer Europe MA EEIG
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameIbrance
    D.3.4Pharmaceutical form Capsule, hard
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNPALBOCICLIB
    D.3.9.1CAS number 571190-30-2
    D.3.9.4EV Substance CodeSUB177204
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number100
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 5
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name IBRANCE
    D.2.1.1.2Name of the Marketing Authorisation holderPfizer Europe MA EEIG
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameIbrance
    D.3.4Pharmaceutical form Capsule, hard
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNPALBOCICLIB
    D.3.9.1CAS number 571190-30-2
    D.3.9.4EV Substance CodeSUB177204
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number75
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Estrogen-receptor positive, human epidermal growth factor receptor-2 negative advanced breast cancer
    E.1.1.1Medical condition in easily understood language
    Advanced breast cancer
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level LLT
    E.1.2Classification code 10072737
    E.1.2Term Advanced breast cancer
    E.1.2System Organ Class 100000004864
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    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
    E.2.2Secondary objectives of the trial
    • 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
    E.2.3Trial contains a sub-study No
    E.3Principal 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 < 60 years and cessation of regular menses for at least 12
    consecutive months with no alternative pathological or physiological
    cause; and serum estradiol and FSH level within the laboratory's
    reference range for postmenopausal females;
    c) Documented bilateral oophorectomy;
    or
    Pre- or peri-menopausal, who must receive a gonadotropin-releasing
    hormone agonist beginning at least 4 weeks prior to first dose of study
    medication.
    4) Histologically or cytologically confirmed diagnosis of advanced
    adenocarcinoma of the breast, not amenable to any potential curative
    intervention
    5) Estrogen Receptor (ER) positive disease defined as follows
    documented by a local laboratory:
    a) [Monotherapy Escalation and Combination Dose Escalation Cohorts]:
    > 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 < 2, or for single probe assessment a HER2 copy
    number < 4
    7) [Monotherapy Escalation and Combination Dose Escalation Cohorts]:
    Refractory to or intolerant of established therapy(ies) known to provide
    clinical benefit for their malignancy
    8) Prior Hormonal Therapy:
    a) [Monotherapy Expansion Cohort]: up to 2 prior lines of endocrine
    therapy for advanced or metastatic breast cancer
    b) [Monotherapy Phase 2]: 1 or 2 prior lines of endocrine therapy for
    advanced or metastatic breast cancer
    c) [Combination Phase 2]: up to 1 prior line of endocrine therapy for
    advanced or metastatic breast cancer
    d) Subjects who will undergo a FES-PET must have discontinued all prior
    ER blocking therapy (e.g., tamoxifen or fulvestrant) for ≥ 60 days before
    the day of the examination at baseline.
    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.
    9) Documented prior response to endocrine therapy for advanced or
    metastatic disease (SD, PR, or CR) lasting > 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
    XML File Identifier: kv+yFHz2HyuQxZcdB7WA72ZBtxA=
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    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 inhibitor is allowed
    12) Evaluable or measurable disease per RECIST v1.1.
    13) Eastern Cooperative Oncology Group (ECOG) Performance Status of
    ≤ 2
    14) All acute toxic effects of any prior anti-tumor therapy resolved to
    Grade ≤ 1 or baseline (with the exception of alopecia [any grade
    permitted])
    15) Adequate organ function defined as follows:
    a) Hematologic: Platelets ≥ 100 × 109/L; Hemoglobin ≥ 9.0 g/dL;
    Absolute Neutrophil Count (ANC) ≥ 1.5 × 109/L (without platelet
    transfusion or any growth factors within previous 7 days of the
    hematologic laboratory values obtained at Screening visit).
    b) Hepatic: Aspartate transaminase (AST) and Alanine transaminase
    (ALT) ≤ 2.5 × upper limit of normal (ULN) or ≤ 5 × ULN in case of liver
    metastases; Total or conjugated bilirubin ≤ 1.5 × ULN.
    c) Renal: Creatinine clearance (CrCl) ≥ 30 mL/min as calculated by the
    Cockcroft Gault method or serum creatinine ≤ 1.5 × ULN
    16) [Premenopausal and perimenopausal female subjects]: Negative
    serum pregnancy test
    17) Male and female subjects of childbearing potential or partners of
    subjects who engage in intercourse must agree to use protocol specified
    method(s) of contraception.
    E.4Principal 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 <
    14 days
    b) Any chemotherapy < 28 days (or 5 half-lives, whichever is shorter)
    c) Any investigational drug therapy < 28 days or 5 half-lives (whichever
    is shorter)
    d) Prior radiotherapy < 14 days (except for palliative radiotherapy to
    peripheral sites without residual toxicity)
    e) Major surgery < 28 days
    f) Minor surgery < 7 days (placement of central venous catheter, fine
    needle aspiration, or endoscopic biliary stent < 1 day is acceptable)
    2) Prior hematopoietic stem cell or bone marrow transplantation
    3) Prior radiotherapy to > 25% of bone marrow
    4) Brain metastases that require immediate treatment or are clinically or
    radiologically unstable (i.e., have been stable for < 1 month). If
    receiving steroids, subjects must be receiving a stable to decreasing
    corticosteroid dose during at least 1 week before enrollment.
    5) Leptomeningeal disease that requires or is anticipated to require
    immediate treatment.
    6) Presence of life-threatening metastatic visceral disease or
    symptomatic pulmonary lymphangitic spread
    7) Other known active cancer(s) likely to require treatment in the next
    year that would impact the assessment of any study endpoints
    8) [Female subjects]: Pregnant or breast-feeding
    9) Unexplained symptomatic endometrial disorders ( Including but not limited to endometrial hyperplasia, dysfunctional uterine bleeding, or
    cysts)
    10) Uncontrolled symptomatic thyroid dysfunction
    11) Impairment of gastrointestinal (GI) absorption for oral medications
    12) Nausea, vomiting, or diarrhea > 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
    E.5 End points
    E.5.1Primary 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
    abnormalities
    • Monotherapy Phase 2 and Combination Phase 2: CBR (CR [+ PR] + SD
    ≥ 24 weeks). PR will only
    be included for patients with measurable disease.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Monotherapy Dose Escalation and Monotherapy Expansion: Single agent
    ZN-c5 will be evaluated at sequentially escalating doses starting with 50 mg
    and up to 1200 mg administered orally, once daily (alternatively, this total
    daily dose may be divided by 2 and administered BID [every 12 hours]),
    using a 28-day cycle (Dose Escalation). During or on completion of the Dose
    Escalation, additional patients may be enrolled onto one or more dose
    levels for the Monotherapy Expansion portion of the study. The decision to
    expand will be based on the PK, safety and available biomarker data.
    E.5.2Secondary 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)
    E.5.2.1Timepoint(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.
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence No
    E.6.9Dose response Yes
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) Yes
    E.7.1.1First administration to humans Yes
    E.7.1.2Bioequivalence study No
    E.7.1.3Other Yes
    E.7.1.3.1Other trial type description
    safety and tolerability
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) Yes
    E.8.2.2Placebo No
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial2
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned4
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA10
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Belarus
    Bosnia and Herzegovina
    Georgia
    Lebanon
    Moldova, Republic of
    Russian Federation
    Serbia
    Turkey
    Ukraine
    Belgium
    Bulgaria
    Croatia
    Hungary
    Lithuania
    United Kingdom
    Czechia
    E.8.7Trial has a data monitoring committee No
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years5
    E.8.9.1In the Member State concerned months0
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years5
    E.8.9.2In all countries concerned by the trial months0
    E.8.9.2In all countries concerned by the trial days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 458
    F.1.3Elderly (>=65 years) Yes
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state30
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 90
    F.4.2.2In the whole clinical trial 458
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    Subject will be treated as per local standard of care
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2020-08-11
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2020-05-21
    P. End of Trial
    P.End of Trial StatusPrematurely Ended
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