Brief Title
ZEN003694 Combined With Talazoparib in Patients With Recurrent Ovarian Cancer
Official Title
Phase ll Study of a BET Inhibitor, ZEN003694, Combined With a PARP Inhibitor, Talazoparib, in Patients With Recurrent Ovarian Cancer
Brief Summary
This Phase 2, open label, study with safety lead in of oral talazoparib in combination with
ZEN003694 given daily in 28-day cycles will enroll patients with recurrent ovarian, fallopian
tube or primary peritoneal carcinoma.
Detailed Description
This study aims to determine how effective the combination of ZEN003694 and talazoparib is
based on how patients respond. ZEN003694 (and developed by Zenith Epigenetics Ltd.) has shown
promising activity in the treatment of solid tumors and hematologic (blood) cancers by
reducing the multiplication of cancer cells. Talazoparib is an extremely effective drug being
developed for the treatment of a variety of human cancers. Talazoparib kills cancer cells by
inhibiting and trapping the enzyme PARP, which is known to be involved in the development of
many types of cancers. These two drugs are not FDA approved in the treatment of ovarian
cancer.
Study Phase
Phase 2
Study Type
Interventional
Primary Outcome
Objective Response
Secondary Outcome
Adverse events at least possibly related to treatment
Condition
Ovarian Cancer
Intervention
ZEN003694
Study Arms / Comparison Groups
ZEN003694 + Talazoparib
Description: ZEN003694: 48.0 mg daily (oral) in 28-day cycles Talazoparib: 0.75 mg daily (oral) at the same time as ZEN003694
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
33
Start Date
April 27, 2022
Completion Date
November 2027
Primary Completion Date
November 2025
Eligibility Criteria
Inclusion Criteria:
1. Females age ≥ 18 years (at time of signing informed consent)
2. ECOG status 0 or 1
3. Pathologically documented ovarian, fallopian tube, or primary peritoneal carcinoma.
4. Progression on prior PARPi (progressed while on PARPi or within 6 months of completing
PARPi therapy) either as maintenance or therapeutic settings.
5. Platinum-sensitive disease: progressed after > 6 months of completing prior platinum
therapy.
6. Have had no more than 5 prior cancer therapy treatment regimens, of which a maximum of
4 were cytotoxic chemotherapy or DNA-damage response agents (likel PARPi) containing
regimens
7. Measurable disease per RECIST 1.1
8. Known BRCA1/2 status
9. Adequate laboratory parameters at Screening including:
1. Hemoglobin ≥ 9.0 gm/dL without transfusions during the 4 weeks prior to Screening
2. Absolute neutrophil count (ANC) ≥ 1.5 × 109/L
3. Platelet count ≥ 150,000/mm3
4. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤ 2.0 x ULN or
if liver function abnormalities due to liver metastases AST and ALT ≤ 5.0 x ULN
5. Total bilirubin ≤ 1.5 x ULN (≤ 3.0 x ULN for subjects with known Gilbert's
syndrome)
6. Calculated (Cockcroft-Gault formula) or measured creatinine clearance ≥ 60 mL/min
7. Prothrombin time (PT), international normalized ratio (INR) and partial
thromboplastin time (PTT) < 1.5 x ULN
10. Female subjects may be enrolled if they are not of childbearing potential, permanently
sterile or who are post-menopausal, defined as no menses for at least 1 year without
an alternative medical cause and FSH levels in the post-menopausal range. Female
subjects of childbearing potential may be enrolled if they consistently and correctly
use a highly effective form of contraception. Highly effective forms of contraception
include: combined (estrogen and progestogen hormonal contraceptives (oral,
intravaginal, transdermal) associated with inhibition of ovulation; progestogen-only
hormonal contraception (oral, injectable, implantable) associated with inhibition of
ovulation; intrauterine device (IUD); intrauterine hormone-releasing system (IUS);
bilateral tubal occlusion; vasectomized partner; sexual abstinence. Female subjects
should not donate eggs from the time point of study drug administration until at least
7 months thereafter
11. Females of childbearing potential must have a negative serum pregnancy test before the
first dose of study drug and must agree to serum pregnancy tests during the study.
12. Females may not be breast-feeding at the first dose of study drug, during study
participation or through 7 months after the last dose of study drug.
13. Ability to swallow capsules and comply with study procedures.
14. Ability to understand and willingness to sign informed consent form prior to
initiation of any study procedures.
15. Patients with previously diagnosed brain metastases are eligible if they have
completed their treatment and have recovered from the acute effects of radiation
therapy or surgery prior to study enrollment, have discontinued corticosteroid
treatment for these metastases for at least 4 weeks and are neurologically stable with
evidence of no disease progression for 6 months.
Exclusion Criteria:
1. Patients with platinum-resistant or primary platinum refractory cancer (progressing
during primary platinum therapy or within 3 months of completing primary first line
platinum therapy)
2. Current or anticipated use of medications known to be strong inhibitors or inducers of
CYP3A4 or substrates of CYP1A2 with narrow therapeutic windows. Strong inhibitors,
inducers or substrates must be discontinued at least 7 days prior to the first
administration of study drug.
3. Current or anticipated use within 7 days prior to the first administration of study
drug, or during the study, of strong P-gp inhibitors. For a list of strong P-gp
inhibitors.
4. Use of oral Factor Xa inhibitors (i.e., rivaroxaban, apixaban, betrixaban, edoxaban
otamixaban, letaxaban, eribaxaban) and Factor IIa inhibitors (i.e., dabigatran). Low
molecular weight heparin is allowed
5. Radiation to >25% of the bone marrow
6. Treatment with a bone-targeted radionuclide within 6 weeks of first dose of study drug
7. Prior chemotherapy or radiation within 3 weeks of study enrollment
8. Have previously received an investigational BET inhibitor (including previous
participation in studies with Zenith drug, ZEN003694)
9. QTcF interval > 470 msec
10. Insufficient recovery from prior treatment-related toxicities except for alopecia,
fatigue and uncontrolled Grade 2 neuropathy
11. Non-healing wound, ulcer or bone fracture (not including a pathological bone fracture
caused by a pre-existing pathological bone lesion)
12. Brain metastases not adequately treated and/or clinically stable (at the discretion of
the Investigator) for at least 6 months prior to the start of study treatment
13. Patients with ovarian carcinosarcoma
14. Known impaired cardiac function or clinically significant cardiac disease such as
uncontrolled supraventricular arrhythmia, ventricular arrhythmia requiring therapy, or
congestive heart failure (New York Heart Association functional class III or IV)
15. Myocardial infarction or unstable angina within 6 months prior to the first
administration of study drug
16. Known myelodysplastic syndrome
17. Other clinically significant co-morbidities, such as uncontrolled pulmonary disease,
active central nervous system disease, active, uncontrolled bacterial, viral, or
fungal infection(s) requiring systemic therapy, or any other condition that could
compromise safety or the patient's participation in the study
18. Impairment of gastrointestinal function that may significantly alter the absorption of
ZEN003694 or talazoparib
19. Other known active cancer requiring therapy at time of study entry or that progressed
or required treatment within 3 years prior to starting study drug (except for skin
basal cell carcinoma or squamous cell carcinoma or in situ cervical cancer)
20. History of infection with (screening tests not required): human immunodeficiency
virus; hepatitis B virus with currently active disease defined as hepatitis B surface
antigen (HBsAg) positivity; or hepatitis C virus unless previously treated and viral
load is undetectable except following situations:
1. HIV-infected patients on effective anti-retroviral therapy with undetectable
viral load within 6 months of enrollment are eligible for this trial.
2. Patients with a known history of Hepatitis B (defined as Hepatitis B surface
antigen [HBsAg] reactive) or known active Hepatitis C virus (defined as HCV RNA
[qualitative] is detected) infection are allowed to be included if: participant
on a stable dose of antiviral therapy, HBV viral load below the limit of
quantification. HCV viral load below the limit of quantification.
21. Major surgery other than diagnostic surgery, dental surgery or stenting within 4 weeks
prior to the first administration of study drug
22. Concurrent participation in another clinical investigational treatment trial.
23. Any other reason that in the opinion of the Investigator would prevent the patient
from completing participation or following the study.
Gender
Female
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Haider Mahdi, MD, 412-648-6417, [email protected]
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT05071937
Organization ID
HCC 21-091
Responsible Party
Sponsor-Investigator
Study Sponsor
Haider Mahdi
Collaborators
Pfizer
Study Sponsor
Haider Mahdi, MD, Principal Investigator, UPMC Hillman Cancer Center
Verification Date
April 2022