| Eligibility |
Inclusion Criteria:
1. Patients aged = 18 years of age at the time of Informed Consent
2. Ability to understand and provide written informed consent prior to undergoing any
study procedures
3. Life expectancy of > 3 months, as estimated by the investigator
4. Histologically confirmed diagnosis (cytology alone excluded) with high-grade serous
ovarian cancer or high-grade endometrioid ovarian cancer, including primary peritoneal
or fallopian tube cancer
5. BRCA mutational status is known (germline and somatic). (For Patients in Phase 2A,
status does not need to be known prior to enrolment)
6. HRD status is known. (For Patients in Phase 2A, status does not need to be known prior
to enrolment)
7. At least 1 measurable lesion to assess response by RECIST v1.1 criteria
8. Archival tumour sample must be available. In the absence of an archival tumour biopsy,
a tumour tissue biopsy will need to be collected prior to enrolment
9. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 at screening
10. Normal organ and bone marrow function:
Haemoglobin = 9.0 g/dL
Absolute neutrophil count (ANC) = 1.5 x 109
Lymphocyte count = 0.5 x 109
Platelet count = 100 x 109
Total bilirubin = 1.5 institutional upper limit normal (ULN)
Serum albumin = 2.5 g/dL
AST and ALT = 2.5 x ULN, unless liver metastases are present in which case they must
be = 5 x ULN
Serum creatinine = 1.5 x ULN or calculated creatinine clearance > 50 mL/min
(calculated using the Cockroft-Gault formula) for patients with creatinine levels
above institutional normal
Patients not receiving anti-coagulant medication must have an INR of = 1.5 and an aPTT
= 1.5 x ULN
11. In the opinion of the Investigator, all other relevant medical conditions must be
well-managed and stable for at least 28 days prior to first administration of study
drug
12. Willing and able to participate in all required evaluations and procedures in this
study protocol
13. Contraception: Each female subject of childbearing potential must agree to use a
highly effective method of contraception (i.e., a method with less than 1% failure
rate per year [e.g., sterilization, hormone implants, hormone injections, some
intrauterine devices, vasectomized partner, or combined birth control pills]) from
screening until 6 months after the last dose of EP0057 or Olaparib, whichever was
taken last. Females of childbearing potential must have a negative serum pregnancy
test at Screening and a negative serum or urine pregnancy test within 24 hours prior
to EP0057 dosing on Day 1 of each Cycle (and must not be lactating). Each female
subject will be considered to be of childbearing potential unless she has been
surgically sterilised by hysterectomy or bilateral tubal ligation/salpingectomy or has
been postmenopausal for at least 1 year.
Cohort 1 patients (Phase 2A and 2B) must be/have:
14. Received no more than 1 prior line of therapy which must be platinum-based
chemotherapy
15. Primary Platinum Resistant after completion of first line platinum-based chemotherapy
Cohort 2 patients (Phase 2A and 2B) must have:
16. Received at least 1 prior line of treatment, 1 of which must be platinum-based
chemotherapy
17. Received a PARP inhibitor in the maintenance setting as their most recent treatment
following a confirmed response by RECIST1.1 (CR or PR) to the last regimen which must
be a platinum-based chemotherapy, with maintenance of response by PARP inhibitor
lasting = 6 months, with subsequent confirmed disease progression as defined by RECIST
v1.1 criteria
Exclusion Criteria:
1. Non-epithelial tumour of the ovary, the fallopian tube or the peritoneum
2. Ovarian tumours of low malignant potential or low grade
3. Prior treatment with a topoisomerase I inhibitor
4. Potent inhibitors or inducers of CYP3A4
5. Concurrent treatment with Coumadin (Warfarin)
6. History of stroke, transient ischemic attack, or myocardial infarction, within 6
months prior to C1D1
7. Brain and/or leptomeningeal metastases that are symptomatic or untreated or that
require current therapy. Brain imaging must not be older than 12 weeks (at the start
of screening). Results with abnormal/unexpected findings of brain MRI should be
discussed with the Medical Monitor as part of the screening process
8. Systemic anti-cancer therapy for the disease under study within 3 weeks or 5
half-lives, whichever is longer, of the first dose of study drug
9. Ongoing toxic manifestations of previous treatments. Exceptions to this are alopecia
or certain Grade 2 toxicities, which in the opinion of the Investigator should not
exclude the patient
10. Patients considered by the Investigator to be at a higher baseline risk for new onset
cystitis
11. Patients with a history, or features suggestive, of bone marrow dysplasia or
myelodysplastic syndrome (MDS) or acute myeloid leukaemia (AML)
12. Confirmed QTcF > 470 msec on screening ECG or congenital long QT syndrome
13. Receiving an investigational anti-cancer treatment concurrently or within 3 weeks or 5
half-lives of either the parent drug or any active metabolite, whichever is longer,
prior to the first dose of study drug
14. Any evidence of severe or uncontrolled systemic conditions (e.g., severe hepatic
impairment) or current unstable or uncompensated respiratory or cardiac conditions
which makes it undesirable for the patient to participate in the study or which could
jeopardize compliance with the protocol
15. Hypersensitivity to EP0057 or any of its excipients
16. Known history of Human Immunodeficiency Virus infection (HIV) (testing is not
required), active infection with SARS-CoV-2, hepatitis B virus (HBV) or hepatitis C
virus (HCV) per institutional protocol. Testing for HBV or HCV status is not necessary
unless clinically indicated or the patient has a history of HBV or HCV infection. All
patients should be tested for an active SARS-CoV-2 infection with an approved
diagnostic test kit
17. Malignant disease other than that being treated in this study, with the following
exceptions:
Malignancies that were treated curatively and have not recurred within 2 years prior
to study treatment
Completely resected basal cell and squamous cell skin cancers
Any malignancy considered to be indolent and that has never required therapy
Completely resected carcinoma in situ of any type
18. Any medical condition that would, in the investigator's judgment, prevent the
patient's participation in the clinical study due to safety concerns, compliance with
clinical study procedures, or interpretation of study results
19. Any major surgical procedure (in the investigator's judgement) within 2 weeks of the
first dose of study drug
20. Pregnant, likely to become pregnant, or lactating women (where pregnancy is defined as
the state of a female after conception and until the termination of gestation)
21. Palliative radiotherapy (e.g., for pain or bleeding) within 6 weeks prior to
randomisation or patients who have not completely recovered previous radiotherapy
(Grade = 2) from the effects of previous radiotherapy
22. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent
drainage procedures (once monthly or more frequently) Note: Patients with indwelling
catheters (e.g.,PleurX) are allowed
23. Hypersensitivity or intolerance (due to safety or other reasons) to PARP inhibitors
Cohort 1 patients (Phase 2A and 2B) who:
24. Have primary platinum refractory disease defined as progression during first line
treatment with 4-6 cycles of platinum based chemotherapy
Cohort 2 patients (Phase 2A and 2B) who:
25. Progress within 6 months during PARP inhibitor maintenance treatment
26. Progress after completion of PARP inhibitor maintenance treatment
|
