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A study investigating the use of EP0031 in patients with cancers having an abnormal RET gene.
EU CTIS ID: 2022-501636-42-00
What this study is testing
Module A: To investigate the safety and tolerability of EP0031 given as monotherapy. Modules B & C: To assess the efficacy of EP0031 given as monotherapy in patients with RET-altered tumours who have received one first generation SRI therapy and in patients with RET-altered tumours with no prior SRI therapy (by RECIST v1.1) Module B: To assess the safety and tolerability in RET fusion positive NSCLC patients who have received a first-generation SRI therapy or who have received no prior SRI therapy.
- Phase I and Phase II (Integrated)- Other
A plain-language read of the study's public EU CTIS listing. The study team confirms the details.
Who can take part
You may be able to join if
- Inclusion criteria applicable to all patients: Male or female patients ≥ 18 years of age with a diagnosis of advanced solid tumour
- Cohort 3: Patients with locally advanced or metastatic MTC with RET mutation who have received one prior first -generation SRI (one prior multi-kinase inhibitor is permitted)
- Cohort 4: Patients with locally advanced or metastatic MTC with RET mutation with no prior SRI (one prior multi-kinase inhibitor is permitted)
- Ability to understand and provide written informed consent before any study-specific procedures
- Inclusion criteria for Module B, Cohorts 5 and 6 (other solid tumours): Solid tumour measurable by RECIST v1.1
- Willing to participate in all required evaluations and procedures
You likely can't join if
- Any known major driver gene alterations other than RET. If a patient has any other significant molecular alterations besides RET, the Investigator should discuss with the Medical Monitor whether the patient can be enrolled
- Any clinically important abnormalities in rhythm, conduction, or morphology on resting ECG (eg, complete left bundle branch block, third-degree heart block, confirmed QTcF > 470 msec on screening ECG). Controlled AF is permitted
- Any factor that increases the risk of QTc prolongation or of arrhythmic events (eg, congenital long QT syndrome, immediate family history of long QT syndrome, or sudden cardiac death under 40 years of age, or requirement for concomitant medications that are known to prolong the QTc interval and cause Torsade de Pointes within < 5 half-lives before the first dose of EP0031
- Active bleeding diatheses; patients on anticoagulation medication should be on a stable dose
- 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 (ie, sustained systolic BP > 150 mmHg or diastolic BP > 90 mmHg)
See the full eligibility criteria
Who can join
- Inclusion criteria applicable to all patients: Male or female patients ≥ 18 years of age with a diagnosis of advanced solid tumour
- Cohort 3: Patients with locally advanced or metastatic MTC with RET mutation who have received one prior first -generation SRI (one prior multi-kinase inhibitor is permitted)
- Cohort 4: Patients with locally advanced or metastatic MTC with RET mutation with no prior SRI (one prior multi-kinase inhibitor is permitted)
- Ability to understand and provide written informed consent before any study-specific procedures
- Inclusion criteria for Module B, Cohorts 5 and 6 (other solid tumours): Solid tumour measurable by RECIST v1.1
- Willing to participate in all required evaluations and procedures
- Inclusion criteria for Module A: Measurable or non-measurable disease as per RECIST v1.1
- Cohort 1b (monotherapy): Patients with locally advanced or metastatic NSCLC with RET fusion who have received one prior first-generation SRI in the first-line setting
- Inclusion criteria 14 as described in the Protocol.
- Cohort 2a (monotherapy, first-line): Patients with locally advanced or metastatic NSCLC with RET fusion
- Inclusion criteria 16 as described in the Protocol.
- Inclusion criteria for Modules B and C, Cohorts 1 and 2 (NSCLC): Measurable disease as defined by RECIST v1.1
- Patients in the paired biopsy cohort must have progressed on prior SRI and have a tumour that is accessible (provided that the Investigator judges the biopsy is technically feasible with minimal risk to the patient and with patient consent)
- Cohort 5: Patients with other locally advanced or metastatic solid tumours with RET fusions (tumour agnostic) who have received one prior first-generation SRI. Up to three prior lines of standard therapies are permitted
- Cohort 6: Patients with other locally advanced or metastatic solid tumours with RET fusions (tumour agnostic) with no prior SRI and no satisfactory alternative treatment option. Up to three prior lines of standard therapies are permitted
- Inclusion criterion for paired biopsy cohort (relevant to Module B, Cohorts 1a, 1b, 3, and 5, only): Patients who have a tumour that is accessible, and this will not interfere with RECIST assessments
- Cohort 1a (monotherapy): Patients with locally advanced or metastatic NSCLC with RET fusion who have received one prior first-generation SRI and one line of platinum-based doublet chemotherapy ± immunotherapy (in any order)
- Ability to swallow and retain oral medication
- Documented RET‐altered cancers as determined by DNA‐ or RNA‐based assay of tumour tissue and/or liquid biopsy
- Patients with RET‐altered cancers that may be eligible for the study, who have not received a prior SRI should be well informed and consented about alternative treatment options including approved RET‐targeted therapies.
- Patients with RET‐altered cancers that may be eligible for the study having progressed on a prior SRI should be well informed and consented about alternative approved therapies, as applicable.
- ECOG performance status of 0 or 1 and life expectancy > 3 months
- Inclusion criteria for Modules B and C, Cohorts 3 and 4 (MTC): Measurable disease as defined by RECIST v1.1
What rules you out
- Any known major driver gene alterations other than RET. If a patient has any other significant molecular alterations besides RET, the Investigator should discuss with the Medical Monitor whether the patient can be enrolled
- Any clinically important abnormalities in rhythm, conduction, or morphology on resting ECG (eg, complete left bundle branch block, third-degree heart block, confirmed QTcF > 470 msec on screening ECG). Controlled AF is permitted
- Any factor that increases the risk of QTc prolongation or of arrhythmic events (eg, congenital long QT syndrome, immediate family history of long QT syndrome, or sudden cardiac death under 40 years of age, or requirement for concomitant medications that are known to prolong the QTc interval and cause Torsade de Pointes within < 5 half-lives before the first dose of EP0031
- Active bleeding diatheses; patients on anticoagulation medication should be on a stable dose
- 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 (ie, sustained systolic BP > 150 mmHg or diastolic BP > 90 mmHg)
- Corneal ulceration or untreated keratitis at the screening ophthalmic assessment
- For MTC patients: involvement of the trachea or oesophagus, or complete encasement of great vessels (eg, aorta or pulmonary artery) that could result in -life-threatening complications due to rapid tumour regression
- Any major surgical procedure within 4 weeks of the first dose of study treatment or planned or anticipated during study treatment
- Chronic glomerulonephritis or renal transplant
- Known active hepatitis B or C infection
- Breastfeeding or pregnancy
- Receipt of any systemic anti-cancer therapy (with the exception of immunotherapy or antibody therapy) and radiotherapy within 2 weeks or < 5 half-lives, whichever is shorter, before the first dose of EP0031. Exceptions: GnRH or LHRH agonists, aromatase inhibitors, or SERMs that the patient has been on for the previous 28 days for the primary cancer are allowed, provided they are not on the list of prohibited concomitant medications
- Receipt of any strong inhibitor or inducer of CYP3A4 within 2 weeks or < 5 half-lives, whichever is shorter, before the first dose of EP0031
- Impaired hepatic or renal function as demonstrated by any of the following laboratory values: a. AST or ALT ≥ 3 × ULN b. Patients with liver metastases: AST or ALT ≥ 5 x ULN c. Total bilirubin ≥ 1.5 × ULN d. CrCl ≤ 50 mL/min (based on Cockcroft Gault)
- Serum calcium, magnesium, or potassium below institutional LLN (can be corrected prior to enrolment)
- Patients with active HIV infection. Patients living with HIV will be eligible if they have CD4+ T-cell count ≥ 350 cells/μL, no history of AIDS-defining opportunistic infections in the past 12 months, and can be managed on a regimen consistent with the permitted concomitant medications defined in this protocol
- Known hypersensitivity to other SRIs or to the excipients of EP0031
- Receipt of any immunotherapy or antibody therapy within 21 days before the first dose of EP0031
- Any other invasive malignancy that has been active or treated within the past 2 years, with the exception of cervical intraepithelial neoplasia and non-melanoma skin cancer
- Any unresolved toxicities from prior systemic therapy greater than CTCAE Grade 1 at the time of starting study drug, with the exception of alopecia and Grade 2 chemotherapy-induced neuropathy
- Spinal cord compression or brain metastases. Patients with stable brain metastases who have completed definitive therapy, and have a stable neurological status for at least 4 weeks after completion of definitive therapy can be enrolled. Patients with asymptomatic brain metastases may be eligible for inclusion if, in the opinion of the Investigator, immediate definitive treatment is not indicated
- Active infection requiring systemic antibiotic, antifungal, or antiviral medication within 7 days prior to first dose of EP0031
- Severe or uncontrolled medical condition (eg, severe Parkinson’s disease, active inflammatory bowel disease, severe chronic obstructive pulmonary disease, or ILD/pneumonitis – patients with a history of ILD/pneumonitis that has recovered to ≤ Grade 1 can be enrolled after discussion with the Medical Monitor)
- Inadequate bone marrow reserve or organ function as demonstrated by any of the following laboratory values: a. ANC < 1.5 × 109/L b. Platelet count < 100 × 109/L c. Haemoglobin < 90 g/L
The study team makes the final eligibility decision.
Where it's taking place
- United Kingdom
- United States
- United Arab Emirates
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 65+ years, 18-64 years. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include United Kingdom; United States; United Arab Emirates. Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.