A Study of EP0031 in Patients With Advanced RET-altered Malignancies

Advanced Solid Tumor Clinical Trial

Official title:

A Modular, Open-label, Phase I/II Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of EP0031 in Patients With Advanced RET-altered Malignancies

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05443126
• Other study ID #: EP0031-101
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: September 30, 2022
• Est. completion date: June 2027

Study information

• Verified date: June 2024
• Source: Ellipses Pharma
• Contact: Sonia Serrano
• Phone: +44 (0)20 3743 0992
• Email: sonia[@]ellipses.life
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The aim of this study is to assess the safety, side effects and effectiveness of EP0031 in patients with advanced RET-altered malignancies

Description:

EP0031 is being investigated in this modular, interventional Phase I/II dose escalation and dose expansion study to investigate the optimal dose in adult patients with advanced RET-altered malignancies. Currently there are no approved RET-targeted treatments for patients who progress on first-generation SRIs. However, it is proposed that EP0031 can overcome resistance mechanisms to first generation SRIs, as EP0031 is a potent and selective RET inhibitor with broad activity against common RET fusions and mutations.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 265
• Est. completion date: June 2027
• Est. primary completion date: December 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

Applicable to all patients:

1. Must be =18 years of age at the time of informed consent, with documented RET-altered malignancy

2. Patients should be well informed and consented about alternative treatment options including approved RET-targeted therapies

3. ECOG performance status of 0 or 1 at screening

4. Ability to understand and provide written informed consent and able to participate in all required evaluations and procedures

Exclusion Criteria:

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

1. Any known major driver gene alterations other than RET.

2. Spinal cord compression or brain metastases. Patients with stable brain metastases can be enrolled.

3. Active infection requiring systemic antibiotic, antifungal, or antiviral medication

4. Severe or uncontrolled medical condition or psychiatric condition

5. Chronic glomerulonephritis or renal transplant

6. Patients with active hepatitis B infection or active hepatitis C

7. Patients with active HIV infection. Patients living with HIV may be eligible if they have adequate CD4+ T-cell count and no history of AIDS-defining opportunistic infections in the past 12 months

8. Receipt of any strong inhibitor or inducer of CYP3A4

9. Impaired hepatic or renal function, inadequate bone marrow reserve or organ function

10. Any clinically important abnormalities in rhythm, conduction, or morphology on resting ECG or any factor that increases the risk of QTc prolongation or of arrhythmic events , or congestive heart failure Grade II-IV according to the New York Heart Association, myocardial infarction, or unstable angina within the previous 6 months

11. Uncontrolled hypertension

12. Corneal ulceration at screening

Related Conditions & MeSH terms

• Advanced Solid Tumor
• Neoplasms

Intervention

Drug:
• EP0031
EP0031 is a potent next-generation selective RET-inhibitor (SRI)

Locations

Country	Name	City	State
Spain	Hospital Universitario Vall d'Hebron	Barcelona
Spain	Hospital Madrid Sanchinarro	Madrid
Spain	Hospital Universitario Ramon y Cajal	Madrid
Spain	University Hospital October 12	Madrid
Spain	Hospital Virgen de la Victoria de Malaga	Málaga
United Kingdom	Guy's Hospital	London
United Kingdom	University College London Hospital	London
United Kingdom	The Christie NHS Foundation Trust - Christie Hospital	Manchester
United Kingdom	Sheffield Teaching Hospitals NHS Foundation Trust	Sheffield
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	RUSH University Medical Center	Chicago	Illinois
United States	Karmanos	Detroit	Michigan
United States	Northwestern University	Evanston	Illinois
United States	Viginia cancer specialists	Fairfax	Virginia
United States	Florida Cancer Specialist	Fort Myers	Florida
United States	MD Anderson Cancer Center	Houston	Texas
United States	University of Kentucky	Lexington	Kentucky
United States	David Geffen School of Medicine at UCLA	Los Angeles	California
United States	Sarah Cannon	Nashville	Tennessee
United States	NYU Langone Health	New York	New York
United States	Providence Portland Medical Centre	Portland	Oregon
United States	Seattle Cancer Care / Fred Hutchinson Cancer Research Center	Seattle	Washington
United States	Washington University	Seattle	Washington
United States	Stanford University	Stanford	California
United States	Georgetown University	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Ellipses Pharma

Countries where clinical trial is conducted

United States,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Module A: Incidence of Dose-limiting Toxicity (DLTs ) during the first 28 days of EP0031 treatment		First 28 days of treatment
Primary	Modules B and C: Overall Response Rate (ORR) as measured using RECIST v1.1		12 months
Secondary	Area under the plasma concentration versus time curve (AUC)	To characterise the pharmacokinetics (PK) of EP0031	First 48 hours after drug administered
Secondary	Maximum Plasma Concentration (Cmax)	To characterise the pharmacokinetics (PK) of EP0031	First 24 hours after drug administered
Secondary	Time taken for drug concentration to fall from half its original value (Half-life)	To characterise the pharmacokinetics (PK) of EP0031	First 72 hours after drug administered