Clinical Trials /

EP0057 in Combination With Olaparib in Advanced Ovarian Cancer

NCT04669002

Description:

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.

Related Conditions:
  • Fallopian Tube Endometrioid Adenocarcinoma
  • Fallopian Tube Serous Adenocarcinoma
  • High Grade Ovarian Serous Adenocarcinoma
  • Ovarian Endometrioid Adenocarcinoma
  • Primary Peritoneal Endometrioid Adenocarcinoma
  • Primary Peritoneal Serous Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: EP0057 in Combination With Olaparib in Advanced Ovarian Cancer
  • Official Title: Phase 2 Study to Evaluate the Safety & Efficacy of EP0057 in Combination With Olaparib in Advanced Ovarian Cancer Patients Who Have: Cohort 1 - Platinum Resistant Disease & Are PARP Inhibitor naïve; Cohort 2 - Had at Least 2 Prior Lines of Therapy Which Must Include at Least 1 Line of Platinum-based Chemotherapy Followed by PARP Inhibitor Maintenance

Clinical Trial IDs

  • ORG STUDY ID: EP0057-201
  • NCT ID: NCT04669002

Conditions

  • Ovarian Cancer

Interventions

DrugSynonymsArms
EP0057Phase 2A Cohort 1
Olaparib tabletsLynparzaPhase 2A Cohort 1

Purpose

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.

Detailed Description

      EP0057-201 is an adaptive Phase 2A/B study in patients with advanced ovarian cancer.

      Phase 2A

      Phase 2A will be comprised of 2 single-arm treatment cohorts:

      Cohort 1 will explore EP0057 in combination with Olaparib in patients with advanced platinum
      resistant ovarian cancer (see inclusion criteria for definition of platinum resistant) who
      are PARP inhibitor naive and who have received no more than 1 prior line of therapy which
      must be platinum-based chemotherapy (n~=30)

      Cohort 2 will explore EP0057 in combination with Olaparib in patients with advanced ovarian
      cancer who have received at least 2 prior lines 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 (n~=30)

      It is anticipated that up to approximately 60 patients (approximately 30 patients per cohort)
      will be enrolled into Phase 2A. Both treatment cohorts will open in parallel and patients
      will be enrolled into each cohort concurrently.

      At the end of Phase 2A, the Safety Review Committee will guide the decision to initiate 1 or
      both cohorts in Phase 2B, or terminate further recruitment into the study.

      Phase 2B

      Phase 2B will be comprised of 2 treatment cohorts, each randomised versus SOC. One or both
      cohorts may be opened concurrently to recruitment:

      Cohort 1 will explore EP0057 in combination with Olaparib compared with SOC chemotherapy
      (TBC) in patients with advanced platinum resistant ovarian cancer who are PARP inhibitor
      naive and who have received no more than 1 prior line of therapy which must be platinum-based
      chemotherapy (n=~132)

      Cohort 2 will explore EP0057 in combination with Olaparib compared with SOC chemotherapy
      (TBC) in patients with advanced ovarian cancer who have received at least 2 prior lines of
      therapy which must include at least 1 line of platinum-based chemotherapy followed by a PARP
      inhibitor as maintenance treatment as their last therapy (n=~192)

      It is anticipated that ~324 patients will be enrolled into Phase 2B. Both treatment cohorts
      may open in parallel and patients may be enrolled into each cohort concurrently.
    

Trial Arms

NameTypeDescriptionInterventions
Phase 2A Cohort 1ExperimentalPatients with advanced platinum resistant ovarian cancer who are PARP inhibitor naive and who have received no more than 1 prior line of therapy which must be platinum-based chemotherapy
  • EP0057
  • Olaparib tablets
Phase 2A Cohort 2ExperimentalPatients with advanced ovarian cancer who have received at least 2 prior lines 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
  • EP0057
  • Olaparib tablets

Eligibility Criteria

        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. PARP inhibitor naïve

         15. Received no more than 1 prior line of therapy which must be platinum-based
             chemotherapy

         16. Either: Stable disease (SD) following treatment with first line platinum based
             chemotherapy OR Primary Platinum Resistant after completion of first line
             platinum-based chemotherapy

             Cohort 2 patients (Phase 2A and 2B) must have:

         17. Received at least 2 prior lines of treatment, 1 of which must be platinum-based
             chemotherapy

         18. 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 and up to 12 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

         25. Have had prior treatment with Bevacizumab

             Cohort 2 patients (Phase 2A and 2B) who:

         26. Progress with ≥ 1 and less than 6 months during PARP inhibitor maintenance treatment

         27. Progress after treatment with PARP inhibitor maintenance treatment lasting > 12 months
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall Response Rate (ORR)
Time Frame:Approximately 18 months
Safety Issue:
Description:Overall Response Rate as measured using RECIST1.1

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Ellipses Pharma

Trial Keywords

  • EP0057
  • Olaparib

Last Updated

December 17, 2020