A research study looking at a new treatment for patients with advanced cancer, to investigate different doses of the experimental study drug, EP0042, in order to determine a dose, which is safe, well tolerated and likely to be effective in treating AML (acute myeloid leukaemia).

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Ellipses Pharma Limited

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

27 Sep 2021 → ongoing

Decision date (initial)

2024-08-06

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Ellipses Pharma Limited, United Kingdom

External identifiers

EU CT number

2024-514588-24-00

EudraCT number

2020-000168-53

ClinicalTrials.gov

NCT04581512

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others, Safety, Pharmacodynamic, Pharmacokinetic, Pharmacogenetic, Pharmacogenomic, Therapy, Efficacy

Core Primary Objectives:
1. To investigate the safety and tolerability of EP0042 given alone or in combination with anti-cancer treatments.

Module 1 Primary Objectives:
1. To investigate the safety and tolerability of EP0042 given as a monotherapy in patients with relapsed or refractory (R/R) AML(AML, MDS or CMML).

Module 2 Primary Objectives:
1. Part A: To evaluate the safety, tolerability, of EP0042 + a Bcl-2 inhibitor (venetoclax) in patients with R/R FLT3 wildtype (WT) AML.
2. Part B: To evaluate the safety, tolerability, of EP0042 in combination with a Bcl-2 inhibitor (venetoclax) + a hypomethylating agent(azacitidine) in patients with R/R FLT3 WT or newly diagnosed AML.

Secondary objectives 3

1. Core Secondary Objectives: 1. To characterizse the pharmacokinetics (PK) of EP0042, given alone or in combination with anti-cancer treatments, after a singledose and at steady state after multiple dosing. 2. To assess the biological and anti-tumor activity of EP0042, given alone or in combination with anticancer treatments.
2. Module 1 Secondary Objectives: 1. To characterizse the (PK) of EP0042, given as a monotherapy, after a single dose and at steady state after multiple dosing. 2. To assess the efficacy of EP0042, given as a monotherapy in patients with relapsed or refractory AML (and MDS or CMML).
3. Module 2 Secondary Objectives: 1. To characterize the PK of EP0042 + combination agent(s), after a single dose and at steady state after multiple dosing. 2. To assess the efficacy of EP0042 + combination agent(s) in patients with AML.

Conditions and MedDRA coding

Acute Myeloid Leukaemia (AML)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. Core Inclusion Criteria: 1. Male or female patients aged ≥ 18 years of age, at the time of informed consent, with histological or cytologicalconfirmation of leukemia. 2. Ability to understand and provide written informed consent before any study-specific procedures, sampling, oranalyses, including access to archival tumor tissue. 3. Ability to swallow and retain oral medication.

Exclusion criteria 1

1. Core Exclusion Criteria: 1. Suspected brain and/or leptomeningeal metastases that are symptomatic or untreated or that require current therapy. 2. Ongoing toxic manifestations of previous treatments that have not reduced to at least Common Terminology Criteria for Adverse Events (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. 3. Creatinine clearance (calculated using Cockcroft-Gault formula, or measured) < 50 mL/min. 4. Receiving an investigational anti-cancer treatment concurrently or within 14 days or five half-lives of either the parent drug or any active metabolite prior to the start of treatment with EP0042. Patients with AML may receive hydroxyurea throughout the screening period and during the first 2 cycles of study treatment in the first module(FIH study). 5. Current refractory nausea and vomiting, malabsorption syndrome, disease significantly affecting gastrointestinal(GI) function, resection of the stomach, extensive small bowel resection that is likely to affect absorption, symptomatic inflammatory bowel disease, partial or complete bowel obstruction, or gastric restrictions and bariatric surgery such as gastric bypass. 6. Known active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection 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. 7. Patients with active human immunodeficiency virus infection (HIV) infection (testing is not required). Patients living with HIV will be eligible if they have CD4+ T-cell count ≥ 350 cells/μL, no history of AIDS-defining opportunistic infections in the past 12 months, and can be managed on a regimen consistent with this protocol's permitted concomitant medications. 8. Malignant disease other than that being treated in this study, with the following exceptions: a. Malignancies that were treated curatively and have not recurred within 2 years prior to study treatment. b. Completely resected basal cell and squamous cell skin cancers. c. Any malignancy considered to be indolent and that has never required therapy. d. Completely resected carcinoma in situ of any type. 9. 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. 10. Any major surgical procedure (in the investigator's judgement) within 2 weeks of the first dose of study drug. 11. 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).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Module 1 Primary Endpoints: 1. Incidence of DLT, adverse events (AEs), serious adverse events (SAEs) and changes in laboratory parameters, physicalexamination, vital signs and electrocardiograms (ECGs).
2. Module 2 Primary Endpoints: 1. Incidence of DLTs, AEs, SAEs and changes in laboratory parameters, physical examination, vital signs and electrocardiograms.

Secondary endpoints 2

1. Module 1 Secondary Endpoints: 1. Plasma PK parameters (AUClast, AUCinf, Cmax and/or Cmin, Tmax, t1/2, CL/F, V/F and/or Vz/F) after single and multiple doses 2. Best overall response (BOR) 3. Duration of response (DOR) 4. Overall survival (OS)
2. Module 2 Secondary Endpoints: 1. Plasma PK parameters (AUClast, AUCinf, Cmax and/or Cmin, Tmax, t1/2, CL/F, V/F and/or Vz/F) of EP0042 and combinationagents after single and multiple doses. 2. BOR 3. DOR 4. Event free survival (EFS) 5. RFS 6. OS

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 10

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Ellipses Pharma Limited

Sponsor organisation

Ellipses Pharma Limited

Address

10 Stratton Street

City

London

Postcode

W1J 8LG

Country

United Kingdom

Scientific contact point

Organisation

Ellipses Pharma Limited

Contact name

Katie Stoddart

Public contact point

Organisation

Ellipses Pharma Limited

Contact name

Katie Stoddart

Third parties 5

Locations

1 EU/EEA country · 2 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Temporary halts 1 · Art. 38 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 12 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications