Purpose

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

Conditions

Eligibility

Eligible Ages
Over 18 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

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

Study Design

Phase
Phase 1/Phase 2
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
RET fusion-positive NSCLC (prior 1st gen SRI)
EP0031 capsules at the recommended phII dose, taken once daily until progressive disease (PD), unacceptable toxicity or patient withdrawal
  • Drug: EP0031
    EP0031 is a potent next-generation selective RET-inhibitor (SRI)
Experimental
RET mutation-positive MTC (prior 1st gen SRI)
EP0031 capsules at the recommended phII dose, taken once daily until progressive disease (PD), unacceptable toxicity or patient withdrawal
  • Drug: EP0031
    EP0031 is a potent next-generation selective RET-inhibitor (SRI)
Experimental
Other RET-altered solid tumours (prior 1st gen SRI)
EP0031 capsules at the recommended phII dose, taken once daily until progressive disease (PD), unacceptable toxicity or patient withdrawal
  • Drug: EP0031
    EP0031 is a potent next-generation selective RET-inhibitor (SRI)
Experimental
RET fusion-positive NSCLC (no prior SRI therapy)
EP0031 capsules at the recommended phII dose, taken once daily until progressive disease (PD), unacceptable toxicity or patient withdrawal
  • Drug: EP0031
    EP0031 is a potent next-generation selective RET-inhibitor (SRI)
Experimental
RET mutation-positive MTC (no prior SRI therapy)
EP0031 capsules at the recommended phII dose, taken once daily until progressive disease (PD), unacceptable toxicity or patient withdrawal
  • Drug: EP0031
    EP0031 is a potent next-generation selective RET-inhibitor (SRI)
Experimental
Other RET-altered solid tumours (no prior SRI therapy)
EP0031 capsules at the recommended phII dose, taken once daily until progressive disease (PD), unacceptable toxicity or patient withdrawal
  • Drug: EP0031
    EP0031 is a potent next-generation selective RET-inhibitor (SRI)

Recruiting Locations

David Geffen School of Medicine at UCLA
Los Angeles 5368361, California 5332921 90095
Contact:
Andrew Gianoukakis, MD
agianoukakis@lundquist.org

Stanford University
Stanford 5398563, California 5332921 94305
Contact:
Emmanuel Ugwu
eugwu@stanford.edu

Georgetown University
Washington D.C. 4140963, District of Columbia 4138106 20057
Contact:
Stephen Liu, MD
Stephen.Liu@gunet.georgetown.edu

Florida Cancer Specialist
Fort Myers 4155995, Florida 4155751 33908
Contact:
Judy Wang, MD
jswang@flcancer.com

Northwestern University
Evanston 4891382, Illinois 4896861 60208
Contact:
Jyoti Patel
jd-patel@northwestern.edu

University of Kentucky
Lexington 4297983, Kentucky 6254925 40506
Contact:
Susanne Arnold
susanne.arnold@uky.edu

Massachusetts General Hospital
Boston 4930956, Massachusetts 6254926 02114
Contact:
Lori Wirth, MD
LWIRTH@mgh.harvard.edu

Memorial Sloan Kettering Cancer Center
New York 5128581, New York 5128638 07920
Contact:
Alex Drilon, MD
drilona@mskcc.org

NYU Langone Health
New York 5128581, New York 5128638 10016
Contact:
Salman Punekar, MD
salman.punekar@nyulangone.org

Providence Portland Medical Centre
Portland 5746545, Oregon 5744337 97213
Contact:
Matthew H Taylor, MD
matthew.taylor@providence.org

Thomas Jefferson University
Philadelphia 4560349, Pennsylvania 6254927 19107
Contact:
Marcia Brose, M.D
marcia.brose@jefferson.edu

Sarah Cannon
Nashville 4644585, Tennessee 4662168 37203
Contact:
Nurse Navigator Hotline
(844) 482-4812

MD Anderson Cancer Center
Houston 4699066, Texas 4736286 77030
Contact:
Yasir Elamin, MD
YYElamin@mdanderson.org

Virginia Cancer Specialists
Fairfax 4758023, Virginia 6254928 22031
Contact:
Alexander Spira, MD
alexander.spira@usoncology.com

Washington University
Seattle 5809844, Washington 5815135 63130
Contact:
Daniel Morgensztern, MD
danielmorgensztern@wustl.edu

Seattle Cancer Care / Fred Hutchinson Cancer Research Center
Seattle 5809844, Washington 5815135 98109
Contact:
Rebecca Wood
206-606-6970
rwood1@fredhutch.org

More Details

Status
Recruiting
Sponsor
Ellipses Pharma

Study Contact

Clinical Trials Team
+44 20 3743 0992
Enquires@ellipses.life

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.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.