EP0057 in Combination With Olaparib in Advanced Ovarian Cancer

Completed · Phase 2

Conditions studied: Ovarian Cancer

In brief

EP0057-201 is a Phase 2A/B adaptive design study. Phase 2A will test EP0057 in combination with Olaparib and Phase 2B, the randomised part of the study, will test EP0057 in combination with Olaparib against SOC chemotherapy. When EP0057 is combined with Olaparib, it is envisaged that the combination should improve therapeutic responses in the recurrent ovarian cancer disease setting. EP0057 is an investigational nanoparticle-drug conjugate administered intravenously. The rationale for developing EP0057 is to enable selective entry of EP0057 into tumour tissue and as a result create preferential accumulation of EP0057, and therefore of the payload Camptothecin, to translate into maximum tumour cell killing.

Key facts

Study ID

NCT04669002

Run by

Ellipses Pharma

People needed

34

Starts

2020-12-14

Expected to finish

2023-05-05

Last updated by the study team

2023-08-02

Who can join

Age: 18 and older. Sex: female. Healthy volunteers: not accepted.

You may qualify if…

• Patients aged ≥ 18 years of age at the time of Informed Consent
• Ability to understand and provide written informed consent prior to undergoing any study procedures
• Life expectancy of > 3 months, as estimated by the investigator
• 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
• BRCA mutational status is known (germline and somatic). (For Patients in Phase 2A, status does not need to be known prior to enrolment)
• HRD status is known. (For Patients in Phase 2A, status does not need to be known prior to enrolment)
• At least 1 measurable lesion to assess response by RECIST v1.1 criteria
• 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
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 at screening
• 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
• 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
• Willing and able to participate in all required evaluations and procedures in this study protocol
• 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:
• Received no more than 1 prior line of therapy which must be platinum-based chemotherapy
• Primary Platinum Resistant after completion of first line platinum-based chemotherapy

You may not qualify if…

• Non-epithelial tumour of the ovary, the fallopian tube or the peritoneum
• Ovarian tumours of low malignant potential or low grade
• Prior treatment with a topoisomerase I inhibitor
• Potent inhibitors or inducers of CYP3A4
• Concurrent treatment with Coumadin (Warfarin)
• History of stroke, transient ischemic attack, or myocardial infarction, within 6 months prior to C1D1
• 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
• 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
• 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
• Patients considered by the Investigator to be at a higher baseline risk for new onset cystitis
• Patients with a history, or features suggestive, of bone marrow dysplasia or myelodysplastic syndrome (MDS) or acute myeloid leukaemia (AML)
• Confirmed QTcF > 470 msec on screening ECG or congenital long QT syndrome
• 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
• 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
• Hypersensitivity to EP0057 or any of its excipients
• 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
• 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
• 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
• Any major surgical procedure (in the investigator's judgement) within 2 weeks of the first dose of study drug
• 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)
• 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

Where it is running

• University of California Irvine — Irvine, California, United States
• Florida Cancer Specialists and Research Institute — Lady Lake, Florida, United States
• Augusta University — Augusta, Georgia, United States
• Massachusetts General Hospital — Boston, Massachusetts, United States
• North Shore Hematology Oncology Associates PC DBA New York Cancer and Blood Specialists — East Setauket, New York, United States
• University of Rochester Medical Center — Rochester, New York, United States
• Duke Cancer Center — Durham, North Carolina, United States
• Magee Women's Hospital of UPMC — Pittsburgh, Pennsylvania, United States
• Prisma Health Cancer Institute — Greenville, South Carolina, United States
• Sarah Cannon — Nashville, Tennessee, United States
• Emily Couric Clinical Cancer Center — Charlottesville, Virginia, United States
• St. Margit Hospital — Budapest, Hungary
• National Institute of Oncology — Budapest, Hungary
• University of Debrecen Clinical Center — Debrecen, Hungary
• Petz Aladár County Teaching Hospital — Győr, Hungary
• Royal Shrewsbury Hospital — Shrewsbury, Shropshire, United Kingdom
• Addenbrooke's Hospital — Cambridge, United Kingdom
• University College Hospital — London, United Kingdom
• Guy's Hospital — London, United Kingdom
• Hammersmith Hospital — London, United Kingdom
• Royal Stoke Hospital — Stoke-on-Trent, United Kingdom

Full record on ClinicalTrials.gov

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