A Study of EP0031-101 in Patients With Advanced RET-altered Malignancies

Study Overview
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Brief Summary
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The aim of this study is to assess the safety, side effects and effectiveness of EP0031 in patients with advanced RET-altered malignancies

Detailed Description
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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.

Official Title
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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

Conditions
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Advanced Solid Tumor

Intervention / Treatment
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* Drug: EP0031


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Applicable to all patients: Must be ≥18 years of age at the time of informed consent, with documented RET-altered malignancy Patients should be well informed and consented about alternative treatment options including approved RET-targeted therapies ECOG performance status of 0 or 1 at screening Ability to understand and provide written informed consent and able to participate in all required evaluations and procedures Exclusion Criteria: Patients 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 Patients with active hepatitis B infection or active hepatitis C 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 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 II-IV according to the New York Heart Association, myocardial infarction, or unstable angina within the previous 6 months Uncontrolled hypertension Corneal ulceration at screening

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RET fusion-positive NSCLC<br>EP0031 capsules at the recommended phII dose, taken once daily until progressive disease (PD), unacceptable toxicity or patient withdrawal | Drug: EP0031<br>* EP0031 is a potent next-generation selective RET-inhibitor (SRI)<br>|
| Experimental: RET mutation-positive MTC<br>EP0031 capsules at the recommended phII dose, taken once daily until progressive disease (PD), unacceptable toxicity or patient withdrawal | Drug: EP0031<br>* EP0031 is a potent next-generation selective RET-inhibitor (SRI)<br>|
| Experimental: Other RET-altered solid tumours<br>EP0031 capsules at the recommended phII dose, taken once daily until progressive disease (PD), unacceptable toxicity or patient withdrawal | Drug: EP0031<br>* EP0031 is a potent next-generation selective RET-inhibitor (SRI)<br>|
| Experimental: RET fusion-positive NSCLC (no prior SRI therapy)<br>EP0031 capsules at the recommended phII dose, taken once daily until progressive disease (PD), unacceptable toxicity or patient withdrawal | Drug: EP0031<br>* EP0031 is a potent next-generation selective RET-inhibitor (SRI)<br>|
| Experimental: RET mutation-positive MTC (no prior SRI therapy)<br>EP0031 capsules at the recommended phII dose, taken once daily until progressive disease (PD), unacceptable toxicity or patient withdrawal | Drug: EP0031<br>* EP0031 is a potent next-generation selective RET-inhibitor (SRI)<br>|
| Experimental: Other RET-altered solid tumours (no prior SRI therapy)<br>EP0031 capsules at the recommended phII dose, taken once daily until progressive disease (PD), unacceptable toxicity or patient withdrawal | Drug: EP0031<br>* EP0031 is a potent next-generation selective RET-inhibitor (SRI)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Module A: Incidence of Dose-limiting Toxicity (DLTs ) during the first 28 days of EP0031 treatment |  | First 28 days of treatment | 
| Modules B and C: Overall Response Rate (ORR) as measured using RECIST v1.1 |  | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the plasma concentration versus time curve (AUC) | To characterise the pharmacokinetics (PK) of EP0031 | First 48 hours after drug administered | 
| Maximum Plasma Concentration (Cmax) | To characterise the pharmacokinetics (PK) of EP0031 | 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 | First 72 hours after drug administered | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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selective RET-inhibitor