EP0057 in Combination With Olaparib in Advanced Ovarian Cancer

NCT04669002 | Completed Phase 2 DMC FDA Drug

• 1 other identifier: EP0057-201
• Study Type: interventional
• Target: 34
• Locations: 3 countries
• Sites: 21

Brief Summary

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.

Conditions

Ovarian Cancer

Keywords

EP0057; Olaparib

Outcome Measures

Primary Outcomes (4)

• Overall Response Rate (ORR)

  Overall Response Rate as measured using RECIST1.1

  Approximately 18 months

• Number of patients with treatment emergent adverse events as assessed by NCI CTCAE version 5

  Approximately 18 months

• Number of patients with related treatment emergent adverse events as assessed by NCI CTCAE version 5

  Approximately 18 months

• Number of patients with serious adverse events

  Approximately 18 months

Study Arms (2)

Phase 2A Cohort 1

EXPERIMENTAL

Patients with advanced platinum resistant ovarian cancer who have received no more than 1 prior line of therapy which must be platinum-based chemotherapy

Drug: EP0057; Drug: Olaparib tablets

Phase 2A Cohort 2

EXPERIMENTAL

Patients with advanced ovarian cancer who have received at least 1 prior line of therapy which must include at least 1 line of platinum-based chemotherapy followed by a PARP inhibitor as maintenance treatment as their last treatment regimen

Drug: EP0057; Drug: Olaparib tablets

Interventions

EP0057 DRUG

EP0057 is an investigational nanoparticle-drug conjugate with a Camptothecin payload, that is administered intravenously

Phase 2A Cohort 1; Phase 2A Cohort 2

Olaparib tablets DRUG

Olaparib is a PARP inhibitor (poly \[adenosine diphosphate-ribose\] polymerase inhibitor)

Also known as: Lynparza

Phase 2A Cohort 1; Phase 2A Cohort 2

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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)

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

Sponsors & Collaborators

• Ellipses Pharma: lead

Study Sites (21)

University of California Irvine

Irvine, California, 92687, United States

Location

Florida Cancer Specialists and Research Institute

Lady Lake, Florida, 32159, United States

Location

Augusta University

Augusta, Georgia, 30912, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

North Shore Hematology Oncology Associates PC DBA New York Cancer and Blood Specialists

East Setauket, New York, 11733, United States

Location

University of Rochester Medical Center

Rochester, New York, 14642, United States

Location

Duke Cancer Center

Durham, North Carolina, 27710, United States

Location

Magee Women's Hospital of UPMC

Pittsburgh, Pennsylvania, 15213, United States

Location

Prisma Health Cancer Institute

Greenville, South Carolina, 29606, United States

Location

Sarah Cannon

Nashville, Tennessee, 37203, United States

Location

Emily Couric Clinical Cancer Center

Charlottesville, Virginia, 22903, United States

Location

St. Margit Hospital

Budapest, 1032, Hungary

Location

National Institute of Oncology

Budapest, 1122, Hungary

Location

University of Debrecen Clinical Center

Debrecen, 4032, Hungary

Location

Petz Aladár County Teaching Hospital

Győr, 9023, Hungary

Location

Royal Shrewsbury Hospital

Shrewsbury, Shropshire, SY3 8XQ, United Kingdom

Location

Addenbrooke's Hospital

Cambridge, CB2 0QQ, United Kingdom

Location

University College Hospital

London, NW1 2PG, United Kingdom

Location

Guy's Hospital

London, SE1 9RT, United Kingdom

Location

Hammersmith Hospital

London, W12 0HS, United Kingdom

Location

Royal Stoke Hospital

Stoke-on-Trent, ST4 6QG, United Kingdom

Location

MeSH Terms

Conditions

Ovarian Neoplasms

Interventions

olaparib

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 2, 2020
• First Posted: December 16, 2020
• Study Start: December 14, 2020
• Primary Completion: February 17, 2023
• Study Completion: May 5, 2023
• Last Updated: August 2, 2023

Record last verified: 2023-08

Locations

GB (6); US (11); HU (4)