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NCT05443126PHASE1, PHASE2Recruiting

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

Ellipses Pharma

Start Date

9/30/2022

Completion Date

3/1/2028

Summary

The aim of this study is to assess the safety, side effects and effectiveness of EP0031 (Lunbotinib) in patients with advanced RET-altered non-small cell lung cancer (NSCLC) in monotherapy and in combination with standard of care (SOC) chemotherapy.

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 NSCLC. Currently there are no approved RET-targeted treatments for patients who progress on first-generation Selective RET Inhibitors (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 for this study and determined the Recommended Phase 2 Dose (RP2D). The study is now in Phase 2, assessing the safety, tolerability and efficacy of EP0031 given in combination with SOC chemotherapy in RET fusion positive NSCLC participants.

Eligibility Criteria

Age Range: 18 years to No maximum

Inclusion Criteria: Applicable to all participants: 1. Must be ≥18 years of age, with documented RET-altered NSCLC 2. Participants 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. Measurable disease defined by RECIST v1.1 6. Must have locally advanced or metastatic NSCLC with RET fusion who are eligible to receive platinum-based doublet chemotherapy. 7. First line patients: Must not have received a Selective RET inhibitor or chemotherapy. Prior adjuvant and neo-adjuvant therapies (chemotherapy, radiotherapy, immunotherapy, biologic therapy, investigational agents), or definitive radiation/chemoradiation with or without regimens including immunotherapy, biologic therapy, investigational agents, are permitted as long as treatment was completed at least 12 months prior. Palliative radiotherapy for symptom management (eg, bone metastases) is permitted up to 2 weeks prior to treatment start. Exclusion Criteria: Participants 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. Participants with active hepatitis B infection or active hepatitis C 7. Participants 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 III-IV according to the New York Heart Association, myocardial infarction, or unstable angina within the previous 6 months 11. Uncontrolled hypertension 12. Corneal ulceration or untreated keratitis at screening

Interventions

DRUG

EP0031

DRUG

Platinum chemotherapy

DRUG

Pemetrexed

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Conditions

NSCLC

Locations

David Geffen School of Medicine at UCLA

Los Angeles, California 90095

United States

Stanford University

Stanford, California 94305

United States

Georgetown University

Washington D.C., District of Columbia 20057

United States

Florida Cancer Specialist

Fort Myers, Florida 33908

United States

University of Miami - Sylvester Comprehensive Cancer Center

Miami, Florida 33136

United States

Florida Cancer Specialists & Research Institute

West Palm Beach, Florida 33401

United States

RUSH University Medical Center

Chicago, Illinois 60612

United States

Northwestern University

Evanston, Illinois 60208

United States

University of Kentucky

Lexington, Kentucky 40506

United States

Massachusetts General Hospital

Boston, Massachusetts 02114

United States

Karmanos

Detroit, Michigan 48201

United States

Memorial Sloan Kettering Cancer Center

New York, New York 07920

United States

NYU Langone Health

New York, New York 10016

United States

The Ohio State University - Comprehensive Cancer Center

Columbus, Ohio 43210

United States

Providence Portland Medical Centre

Portland, Oregon 97213

United States

Thomas Jefferson University

Philadelphia, Pennsylvania 19107

United States

Sarah Cannon Research Institute

Nashville, Tennessee 37203

United States

MD Anderson Cancer Center

Houston, Texas 77030

United States

Virginia Cancer Specialists

Fairfax, Virginia 22031

United States

Washington University - School of Medicine

Seattle, Washington 63130

United States

University of Washington - Fred Hutchinson Cancer Center

Seattle, Washington 98109

United States

Institut Bergonié

Bordeaux,

France

Centre François Baclesse

Caen,

France

Centre Léon Bérard

Lyon,

France

Assistance Publique - Hôpitaux de Marseille

Marseille,

France

Institut Gustave Roussy

Paris,

France

Charité Comprehensive Cancer Center

Berlin,

Germany

Universitätsklinikum Köln

Cologne,

Germany

Ludwig-Maximilians-Universität München (LMU)

München,

Germany

Centro di Riferimento Oncologico IRCCS

Aviano,

Italy

IRCCSS AOU Bologna

Bologna,

Italy

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan,

Italy

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Roma,

Italy

Istituto Nazionale Tumori Regina Elena

Roma,

Italy

Azienda Ospedaliero-Universitaria San Luigi Gonzaga

Torino,

Italy

Uniwersyteckie Centrum Kliniczne

Gdansk,

Poland

Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie

Warsaw,

Poland

Hospital Universitario de A Coruña

A Coruña,

Spain

Hospital Universitario Vall d'Hebron

Barcelona, 08035

Spain

Hospital Universitario Insular de Gran Canaria

Las Palmas de Gran Canaria,

Spain

Hospital Universitario Ramon y Cajal

Madrid, 28034

Spain

Hospital Universitario 12 de Octubre

Madrid, 28041

Spain

Hospital Madrid Sanchinarro

Madrid, 28050

Spain

Hospital Virgen de la Victoria de Malaga

Málaga, 29010

Spain

Tawam Hospital

Al Ain City, Abu Dhabi Emirate

United Arab Emirates

Sheik Shakhbout Medical City (SSMC)

Abu Dhabi, 11001

United Arab Emirates

Cleveland Clinic Abu Dhabi (CCAD)

Abu Dhabi, 112412

United Arab Emirates

University College London Hospital (UCLH)

London, NW1 2BU

United Kingdom

Guy's and St Thomas' Hospital NHSFT

London, SE1 9RT

United Kingdom

The Royal Marsden NHSFT

London, SW36JJ

United Kingdom

The Christie Hospital NHSFT

Manchester, M20 4BX

United Kingdom

Sheffield Teaching Hospitals NHSFT

Sheffield, S10 2JF

United Kingdom