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

Ellipses Pharma

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Advanced Solid Tumor

Treatments: Drug: EP0031

Study type: Interventional

Funder types: Industry

Identifiers

NCT05443126

EP0031-101

Details and patient eligibility

About

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

Full 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 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. Phase I (dose escalation and optimization) has completed and a RP2D has been selected for Phase II.

Enrollment: 265 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

Applicable to all patients:

1. Must be ≥18 years of age, with documented RET-altered cancers
2. Patients 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. Additional cohort specific criteria apply

Exclusion criteria

Patients 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. Patients with active hepatitis B infection or active hepatitis C
7. 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
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 II-IV according to the New York Heart Association, myocardial infarction, or unstable angina within the previous 6 months
11. Uncontrolled hypertension
12. Corneal ulceration at screening

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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265 participants in 6 patient groups

RET fusion-positive NSCLC (prior 1st gen SRI)

Experimental group

Description:

EP0031 capsules at the recommended phII dose, taken once daily until progressive disease (PD), unacceptable toxicity or patient withdrawal

Treatment:

Drug: EP0031

RET mutation-positive MTC (prior 1st gen SRI)

Experimental group

Description:

EP0031 capsules at the recommended phII dose, taken once daily until progressive disease (PD), unacceptable toxicity or patient withdrawal

Treatment:

Drug: EP0031

Other RET-altered solid tumours (prior 1st gen SRI)

Experimental group

Description:

EP0031 capsules at the recommended phII dose, taken once daily until progressive disease (PD), unacceptable toxicity or patient withdrawal

Treatment:

Drug: EP0031

RET fusion-positive NSCLC (no prior SRI therapy)

Experimental group

Description:

EP0031 capsules at the recommended phII dose, taken once daily until progressive disease (PD), unacceptable toxicity or patient withdrawal

Treatment:

Drug: EP0031

RET mutation-positive MTC (no prior SRI therapy)

Experimental group

Description:

EP0031 capsules at the recommended phII dose, taken once daily until progressive disease (PD), unacceptable toxicity or patient withdrawal

Treatment:

Drug: EP0031

Other RET-altered solid tumours (no prior SRI therapy)

Experimental group

Description:

EP0031 capsules at the recommended phII dose, taken once daily until progressive disease (PD), unacceptable toxicity or patient withdrawal

Treatment:

Drug: EP0031