Clinical trial NCT05443126: A Study of EP0031 in Patients With Advanced RET-altered Malignancies
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Advanced Solid Tumor
Keywords: selective RET-inhibitor
Lead sponsor: Ellipses Pharma
Sponsor class: INDUSTRY
First posted: 2022-07-05
Enrollment: 265
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Detailed 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. Phase I (dose escalation and optimization) has completed and a RP2D has been selected for Phase II.

Eligibility criteria: Inclusion Criteria:

Applicable to all patients:

1. Must be ≥18 years of age, with documented RET-altered cancers
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 and life expectancy \>3 months at screening
4. Ability to understand and provide written informed consent and able to participate in all required evaluations and procedures
5. Additional cohort specific criteria apply

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

Primary outcomes:
measure: Module A: Incidence of Dose-limiting Toxicity (DLTs ) during the first 28 days of EP0031 treatment
timeFrame: First 28 days of treatment
measure: Modules B and C: Overall Response Rate (ORR) as measured using RECIST v1.1
timeFrame: 12 months
Secondary outcomes:
measure: Area under the plasma concentration versus time curve (AUC)
timeFrame: First 48 hours after drug administered
measure: Maximum Plasma Concentration (Cmax)
timeFrame: First 24 hours after drug administered
measure: Time taken for drug concentration to fall from half its original value (Half-life)
timeFrame: First 72 hours after drug administered
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: David Geffen School of Medicine at UCLA
state: California
city: Stanford
country: United States
facility: Stanford University
state: California
city: Washington
country: United States
facility: Georgetown University
state: District of Columbia
city: Fort Myers
country: United States
facility: Florida Cancer Specialist
state: Florida
city: Chicago
country: United States
facility: RUSH University Medical Center
state: Illinois
city: Evanston
country: United States
facility: Northwestern University
state: Illinois
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Detroit
country: United States
facility: Karmanos
state: Michigan
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: New York
country: United States
facility: NYU Langone Health
state: New York
city: Portland
country: United States
facility: Providence Portland Medical Centre
state: Oregon
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Nashville
country: United States
facility: Sarah Cannon
state: Tennessee
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Fairfax
country: United States
facility: Viginia cancer specialists
state: Virginia
city: Seattle
country: United States
facility: Washington University
state: Washington
city: Seattle
country: United States
facility: Seattle Cancer Care / Fred Hutchinson Cancer Research Center
state: Washington
city: Marseille
country: France
facility: Assistance publique - Hôpitaux de Marseille
state: Bouches-du-Rhône
city: Bordeaux
country: France
facility: Center Bergonié
state: Gironde
city: Villejuif
country: France
facility: Institut Gustave-Roussy
state: Paris
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Madrid
country: Spain
facility: University Hospital October 12
city: Madrid
country: Spain
facility: Hospital Madrid Sanchinarro
city: Málaga
country: Spain
facility: Hospital Virgen de la Victoria de Malaga
city: Al Ain
country: United Arab Emirates
facility: Tawam Hospital
state: Abu Dhabi
city: Abu Dhabi
country: United Arab Emirates
facility: Sheik Shakhbout Medical City (SSMC)
city: Abu Dhabi
country: United Arab Emirates
facility: Cleveland Clinic Abu Dhabi (CCAD)
city: London
country: United Kingdom
facility: University College London Hospital
city: London
country: United Kingdom
facility: Guy's Hospital
city: London
country: United Kingdom
facility: The Royal Marsden NHS Foundation Trust
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust - Christie Hospital
city: Sheffield
country: United Kingdom
facility: Sheffield Teaching Hospitals NHS Foundation Trust
Study officials:
References: