NSCLCPhase 1/2NCT05443126

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

A Phase 1/2 study testing EP0031, Platinum chemotherapy and Pemetrexed in people with NSCLC, run by Ellipses Pharma at 52 sites in 8 countries.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts

Official record

Search all trials

Trial 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. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: NSCLC
What is being tested?: EP0031, Platinum chemotherapy and Pemetrexed
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 265 participants
Where: 52 sitesin 8 countries
Study dates: 30 Sep 2022to Mar 2028
Phase: Phase 1/2
Are there results?: Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Who cannot join

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

Show all 13Show fewer

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

Trial locations and contacts

52 sites in 8 countries. Contact the study team or a site near you to ask about taking part.

Clinical Trials Team contact

+44 20 3743 0992

Enquires@ellipses.life

Country

City, postcode or hospital

Sites recruiting now only

52 sites in 8 countries

United States21 sites, 15 recruiting

Massachusetts General Hospital
Boston, Massachusetts, 02114
Recruiting
RUSH University Medical Center
Chicago, Illinois, 60612
Terminated
The Ohio State University - Comprehensive Cancer Center
Columbus, Ohio, 43210
Recruiting
Karmanos
Detroit, Michigan, 48201
Terminated
Northwestern University
Evanston, Illinois, 60208
Recruiting
Virginia Cancer Specialists
Fairfax, Virginia, 22031
Recruiting
Florida Cancer Specialist
Fort Myers, Florida, 33908
Terminated
MD Anderson Cancer Center
Houston, Texas, 77030
Recruiting
University of Kentucky
Lexington, Kentucky, 40506
Terminated
David Geffen School of Medicine at UCLA
Los Angeles, California, 90095
Recruiting
University of Miami - Sylvester Comprehensive Cancer Center
Miami, Florida, 33136
Recruiting
Sarah Cannon Research Institute
Nashville, Tennessee, 37203
Terminated
Memorial Sloan Kettering Cancer Center
New York, New York, 07920
Recruiting
NYU Langone Health
New York, New York, 10016
Recruiting
Thomas Jefferson University
Philadelphia, Pennsylvania, 19107
Withdrawn
Providence Portland Medical Centre
Portland, Oregon, 97213
Recruiting
Washington University - School of Medicine
Seattle, Washington, 63130
Recruiting
University of Washington - Fred Hutchinson Cancer Center
Seattle, Washington, 98109
Recruiting
Stanford University
Stanford, California, 94305
Recruiting
Georgetown University
Washington D.C., District of Columbia, 20057
Recruiting
Florida Cancer Specialists & Research Institute
West Palm Beach, Florida, 33401
Recruiting

Other trials in United States

Spain7 sites, 7 recruiting

Hospital Universitario de A Coruña
A Coruña
Recruiting
Hospital Universitario Vall d'Hebron
Barcelona, 08035
Recruiting
Hospital Universitario Insular de Gran Canaria
Las Palmas de Gran Canaria
Recruiting
Hospital Universitario Ramon y Cajal
Madrid, 28034
Recruiting
Hospital Universitario 12 de Octubre
Madrid, 28041
Recruiting
Hospital Madrid Sanchinarro
Madrid, 28050
Recruiting
Hospital Virgen de la Victoria de Malaga
Málaga, 29010
Recruiting

Other trials in Spain

Italy6 sites, 6 recruiting

Centro di Riferimento Oncologico IRCCS
Aviano
Recruiting
IRCCSS AOU Bologna
Bologna
Recruiting
Fondazione IRCCS Istituto Nazionale dei Tumori
Milan
Not yet recruiting
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Roma
Recruiting
Istituto Nazionale Tumori Regina Elena
Roma
Recruiting
Azienda Ospedaliero-Universitaria San Luigi Gonzaga
Torino
Recruiting

Other trials in Italy

France5 sites, 5 recruiting

Institut Bergonié
Bordeaux
Recruiting
Centre François Baclesse
Caen
Recruiting
Centre Léon Bérard
Lyon
Recruiting
Assistance Publique - Hôpitaux de Marseille
Marseille
Recruiting
Institut Gustave Roussy
Paris
Recruiting

Other trials in France

United Kingdom5 sites, 4 recruiting

University College London Hospital (UCLH)
London, NW1 2BU
Recruiting
Guy's and St Thomas' Hospital NHSFT
London, SE1 9RT
Recruiting
The Royal Marsden NHSFT
London, SW36JJ
Recruiting
The Christie Hospital NHSFT
Manchester, M20 4BX
Recruiting
Sheffield Teaching Hospitals NHSFT
Sheffield, S10 2JF
Withdrawn

Other trials in United Kingdom

Germany3 sites, 3 recruiting

Charité Comprehensive Cancer Center
Berlin
Recruiting
Universitätsklinikum Köln
Cologne
Recruiting
Ludwig-Maximilians-Universität München (LMU)
München
Not yet recruiting

Other trials in Germany

United Arab Emirates3 sites, 3 recruiting

Sheik Shakhbout Medical City (SSMC)
Abu Dhabi, 11001
Recruiting
Cleveland Clinic Abu Dhabi (CCAD)
Abu Dhabi, 112412
Recruiting
Tawam Hospital
Al Ain City, Abu Dhabi Emirate
Recruiting

Other trials in United Arab Emirates

Poland2 sites, 2 recruiting

Uniwersyteckie Centrum Kliniczne
Gdansk
Recruiting
Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie
Warsaw
Not yet recruiting

Other trials in Poland

About this study

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

Read the 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.

Conditions: NSCLC
Being tested: EP0031, Platinum chemotherapy, Pemetrexed
Keywords: selective RET-inhibitor, NSCLC, RET, EP0031, A400, Chemotherapy, lunbotinib

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

EP0031Drug
EP0031 is a potent next-generation selective RET-inhibitor (SRI)
Platinum chemotherapyDrug
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.
PemetrexedDrug
Pemetrexed is a chemotherapy medication and antifolate metabolic inhibitor administered as an IV infusion according to local practice and labels.

Study groups in NCT05443126
Study group	Role	What they receive
RET fusion-positive NSCLC (treatment naïve i.e. no prior therapy) in combination w/ SOC chemotherapy	Experimental	Cohort 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 Receives: Drug: EP0031; Drug: Platinum chemotherapy; Drug: Pemetrexed
RET fusion-positive NSCLC (post-SRI) in combination w/ SOC chemotherapy	Experimental	Cohort 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 Receives: Drug: EP0031; Drug: Platinum chemotherapy; Drug: Pemetrexed

What is being measured

The primary outcome is the main question the study is designed to answer.

Module B: Incidence of Dose-limiting Toxicity (DLTs ) during the first 21 days of EP0031 given in combination with SOC chemotherapy treatment
Measured: First 21 days of treatment

Secondary outcomes (4)

Module B: Overall Response Rate (ORR) as measured using RECIST v1.1
Measured: 12 months
Area under the plasma concentration versus time curve (AUC)
To characterise the pharmacokinetics (PK) of EP0031
Measured: First 24 hours after drug administered
Maximum Plasma Concentration (Cmax)
To characterise the pharmacokinetics (PK) of EP0031
Measured: First 24 hours after drug administered
Time taken for drug concentration to fall from half its original value (Half-life)
To characterise the pharmacokinetics (PK) of EP0031
Measured: First 24 hours after drug administered

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

30 Sep 2022Mar 2028

First posted5 Jul 2022
Study start30 Sep 2022
Primary completionMar 2027 (estimated)
Study completionMar 2028 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for NSCLCStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 265 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT05443126
Sponsor's protocol ID: EP0031-101
Status last verified: Jun 2026
First submitted: 24 Jun 2022
Last updated: 1 Jul 2026
Results posted: No
FDA-regulated drug: Yes
FDA-regulated device: No

Study at a glance

From the registry record, last updated by the sponsor on 1 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT05443126
Acronym / sponsor ID: EP0031-101
Conditions: NSCLC
Keywords: selective RET-inhibitor, NSCLC, RET, EP0031, A400, Chemotherapy, lunbotinib
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Recruiting
Enrolment: 265 participants (estimated)
Lead sponsor: Ellipses PharmaIndustry (pharma, biotech, devices)
Study start: 30 Sep 2022 (actual)
Primary completion: Mar 2027 (estimated)
Study completion: Mar 2028 (estimated)
First posted: 5 Jul 2022 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
RET fusion-positive NSCLC (treatment naïve i.e. no prior therapy) in combination w/ SOC chemotherapy	Experimental	Drug: EP0031, Drug: Platinum chemotherapy, Drug: PemetrexedCohort 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	Experimental	Drug: EP0031, Drug: Platinum chemotherapy, Drug: PemetrexedCohort 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

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (8 listed)

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

Key exclusion criteria (13 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
EP0031EP0031 is a potent next-generation selective RET-inhibitor (SRI)	Drug	RET fusion-positive NSCLC (post-SRI) in combination w/ SOC chemotherapy, RET fusion-positive NSCLC (treatment naïve i.e. no prior therapy) in combination w/ SOC chemotherapy
Platinum chemotherapyOne 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.	Drug	RET fusion-positive NSCLC (post-SRI) in combination w/ SOC chemotherapy, RET fusion-positive NSCLC (treatment naïve i.e. no prior therapy) in combination w/ SOC chemotherapy
PemetrexedPemetrexed is a chemotherapy medication and antifolate metabolic inhibitor administered as an IV infusion according to local practice and labels.	Drug	RET fusion-positive NSCLC (post-SRI) in combination w/ SOC chemotherapy, RET fusion-positive NSCLC (treatment naïve i.e. no prior therapy) in combination w/ SOC chemotherapy

Primary outcome

Module B: Incidence of Dose-limiting Toxicity (DLTs ) during the first 21 days of EP0031 given in combination with SOC chemotherapy treatment
Time frame: First 21 days of treatment

4 secondary outcomes

Module B: Overall Response Rate (ORR) as measured using RECIST v1.1
Time frame: 12 months
Area under the plasma concentration versus time curve (AUC)
Time frame: First 24 hours after drug administered
Maximum Plasma Concentration (Cmax)
Time frame: First 24 hours after drug administered
Time taken for drug concentration to fall from half its original value (Half-life)
Time frame: First 24 hours after drug administered

Results and safety

This study is still under way. Results are not available in the source record yet.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 1 Jul 2026.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.

Clinical Trials Team contact

+44 20 3743 0992

Enquires@ellipses.life

52 sites in 8 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing EP0031, Platinum chemotherapy and Pemetrexed in people with NSCLC, run by Ellipses Pharma at 52 sites in 8 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 1 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 52 sites in United States, Spain, Italy, France, United Kingdom and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Clinical Trials Team (+44 20 3743 0992, Enquires@ellipses.life), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Module B: Incidence of Dose-limiting Toxicity (DLTs ) during the first 21 days of EP0031 given in combination with SOC chemotherapy treatment (time frame: First 21 days of treatment). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05443126.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Jul 2026.