A Study of EP0031 (Lunbotinib) in Patients With Advanced RET-altered Malignancies
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
1 other identifier
interventional
265
8 countries
52
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Sep 2022
Longer than P75 for phase_1
52 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 24, 2022
CompletedFirst Posted
Study publicly available on registry
July 5, 2022
CompletedStudy Start
First participant enrolled
September 30, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 1, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
March 1, 2028
July 1, 2026
June 1, 2026
4.4 years
June 24, 2022
June 29, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Module B: Incidence of Dose-limiting Toxicity (DLTs ) during the first 21 days of EP0031 given in combination with SOC chemotherapy treatment
First 21 days of treatment
Secondary Outcomes (4)
Module B: Overall Response Rate (ORR) as measured using RECIST v1.1
12 months
Area under the plasma concentration versus time curve (AUC)
First 24 hours after drug administered
Maximum Plasma Concentration (Cmax)
First 24 hours after drug administered
Time taken for drug concentration to fall from half its original value (Half-life)
First 24 hours after drug administered
Study Arms (2)
RET fusion-positive NSCLC (treatment naïve i.e. no prior therapy) in combination w/ SOC chemotherapy
EXPERIMENTALCohort for eligible patients with no prior first line treatment with a 1st gen SRI or chemotherapy. EP0031 capsules at the recommended dose, taken once daily, in combination with doublet platinum-based SOC chemotherapy, both administered on Day 1 of 21-day cycles for 4 cycles, followed by EP0031 plus pemetrexed maintenance until progressive disease (PD), unacceptable toxicity or patient withdrawal
RET fusion-positive NSCLC (post-SRI) in combination w/ SOC chemotherapy
EXPERIMENTALCohort for eligible patients treated previously with a 1st gen SRI. COHORT IS NOW CLOSED TO RECRUITMENT. EP0031 capsules at the recommended dose, taken once daily, in combination with doublet platinum-based SOC chemotherapy, both administered on Day 1 of 21-day cycles for 4 cycles, followed by EP0031 plus pemetrexed maintenance until progressive disease (PD), unacceptable toxicity or patient withdrawal
Interventions
EP0031 is a potent next-generation selective RET-inhibitor (SRI)
One of either Cisplatin or Carboplatin. Both agents are potent platinum-based antineoplastic/alkylating agents administered as an IV infusion according to local practice and labels.
Pemetrexed is a chemotherapy medication and antifolate metabolic inhibitor administered as an IV infusion according to local practice and labels.
Eligibility Criteria
You may qualify if:
- Applicable to all participants:
- Must be ≥18 years of age, with documented RET-altered NSCLC
- Participants should be well informed and consented about alternative treatment options including approved RET-targeted therapies
- ECOG performance status of 0 or 1 and life expectancy \>3 months at screening
- Ability to understand and provide written informed consent and able to participate in all required evaluations and procedures
- Measurable disease defined by RECIST v1.1
- Must have locally advanced or metastatic NSCLC with RET fusion who are eligible to receive platinum-based doublet chemotherapy.
- 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.
You may not qualify if:
- Participants with any of the following will not be included in the study:
- Any known major driver gene alterations other than RET.
- Spinal cord compression or brain metastases. Patients with stable brain metastases can be enrolled.
- Active infection requiring systemic antibiotic, antifungal, or antiviral medication
- Severe or uncontrolled medical condition or psychiatric condition
- Chronic glomerulonephritis or renal transplant
- Participants with active hepatitis B infection or active hepatitis C
- 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
- Receipt of any strong inhibitor or inducer of CYP3A4
- Impaired hepatic or renal function, inadequate bone marrow reserve or organ function
- 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
- Uncontrolled hypertension
- Corneal ulceration or untreated keratitis at screening
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Ellipses Pharmalead
Study Sites (52)
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
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 24, 2022
First Posted
July 5, 2022
Study Start
September 30, 2022
Primary Completion (Estimated)
March 1, 2027
Study Completion (Estimated)
March 1, 2028
Last Updated
July 1, 2026
Record last verified: 2026-06