Evaluating a new treatment for advanced blood cancers

A Modular, Multipart, Multi-arm, Open-label, Phase I/IIa Study to Evaluate the Safety and Tolerability of EP0042 Alone and in Combination With Anti-cancer Treatments in Patients With Advanced Malignancies

This study is testing a new drug called EP0042 to see if it is safe and effective for people with advanced blood cancers like AML, CMML, and MDS.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 70 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Ellipses Pharma (Industry-sponsored)
• Drugs / interventions: gilteritinib, quizartinib
• Locations: 6 sites (Perth, Western Australia and 5 other locations)
• Trial ID: NCT04581512 on ClinicalTrials.gov

What this trial studies

This study investigates the safety and tolerability of an experimental drug, EP0042, in patients with advanced blood cancers such as Acute Myeloid Leukemia (AML), Chronic Myelomonocytic Leukemia (CMML), and Myelodysplastic Syndromes (MDS). It aims to determine the appropriate dosing that is safe and effective for these patients. Participants will receive the drug over a treatment cycle of 28 days, and their responses will be monitored closely to assess the drug's impact.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with confirmed diagnoses of AML, CMML, or MDS who have relapsed or are refractory to previous therapies.

Not a fit: Patients with early-stage blood cancers or those who are not able to tolerate oral medications may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with advanced blood cancers who have limited treatment choices.

How similar studies have performed: Other studies have shown promise with similar investigational drugs in treating advanced blood cancers, indicating a potential for success with this approach.

Eligibility criteria

General

1. Male or female patients aged ≥ 18 years of age, at the time of informed consent, with histological or cytological confirmation of AML
2. Ability to understand and provide written informed consent before any study-specific procedures, sampling, or analyses, including access to archival tumor tissue
3. Ability to swallow and retain oral medication
4. Sufficient life expectancy to allow the patient to complete at least 1 cycle (28 days) of the treatment period.
5. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2 at screening
6. 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
7. Patients with pathologically confirmed/documented AML or MDS, as defined by the 2022 European LeukaemiaNet (ELN) recommendations, or CMML, as defined by World Health Organization (WHO) criteria, who have relapsed from or are refractory to previous therapy and have failed all (or are not eligible for/intolerant to) available approved therapies for their disease.
8. Patients with relapsed/refractory FLT3 WT AML.
9. Previous exposure to venetoclax, hypomethylating agent and/or FLT3 inhibitors (gilteritinib, midostorin, quizartinib, sorafenib) is allowed for relapsed/refractory AML patients.
10. Mutation status of patients must be known at trial entry.
11. Female patients should either be of non-child-bearing potential or must agree to use highly effective methods of contraception from Screening until 6 months following administration of the last dose of study drug
12. Male patients must use double barrier contraception from enrolment through treatment and for 6 months following administration of the last dose of study drug

5.2 Core Exclusion Criteria

Patients with any of the following will not be included in the study:

Disease Under Study and Prior Anticancer Treatment

1. Suspected brain and/or leptomeningeal metastases that are symptomatic or untreated or that require current therapy
2. Acute promyelocytic leukemia (FAB:M3)
3. Systemic anti-cancer therapy for the disease under study within 2 weeks of the first dose of study treatment. If the previous anti-cancer therapy has a very long half-life and may interact with EP0042, e.g. a strong CYP3A4 inhibitor, the washout period may need to be increased for safety reasons but will be no longer than 3 weeks (Concomitant hydroxyurea is acceptable and will be permitted throughout the screening period and during first 6 cycles of study treatment)
4. Ongoing toxic manifestations of previous treatments that have not reduced to at least CTCAE Grade 1. Exceptions to this are alopecia or certain Grade 2 treatment related toxicities, which in the opinion of the Investigator should not exclude the patient.
5. Transplantation (allogeneic or autologous) within last 90 days, or on active immunosuppressive therapy for graft versus host disease in last 2 weeks

   Laboratory Parameters
6. Patient with any out-of-range laboratory values defined as shown below.

   • Creatinine clearance (calculated using Cockcroft-Gault formula, or measured) \< 50 mL/ min
7. Inadequate liver function as demonstrated by

   * total serum bilirubin ≥ 1.5 times the upper limits of normal range (ULN) or
   * ALT ≥3 times the ULN or
   * AST ≥3 times the ULN or
   * AST or ALT ≥5 times the ULN in the presence of liver involvement by leukemia

Where this trial is running

Perth, Western Australia and 5 other locations

• Royal Perth Hospital — Perth, Western Australia, Australia (Recruiting)
• Amsterdam UMC — Amsterdam, Amsterdam, Netherlands (Recruiting)
• Erasmus MC — Rotterdam, Rotterdam, Netherlands (Recruiting)
• University College London Hospital — London, London, United Kingdom (Recruiting)
• The Royal Marsden — London, UK, United Kingdom (Recruiting)
• The Christie Hospital — Manchester, United Kingdom (Recruiting)

Study contacts

• Principal investigator: David Taussig — The Royal Marsden, UK
• Study coordinator: Clinical Trials Team

Conditions Acute Myeloid Leukemia; Chronic Myelomonocytic Leukemia; Myelodysplastic Syndromes