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

Phase 1

Recruiting

• Conditions: Advanced Solid Tumor
• Interventions: Drug: EP0031

• Registration Number: NCT05443126
• Lead Sponsor: Ellipses Pharma

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2022-06-24
• Study First Submitted QC: 2022-07-01
• Study First Posted: 2022-07-05
• Study Start: 2022-09-30
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-17
• Last Update Posted: 2024-12-18
• Primary Completion: 2026-12
• Study Completion: 2027-06

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 265

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
RET mutation-positive MTC (prior 1st gen SRI)	EP0031	EP0031 capsules at the recommended phII dose, taken once daily until progressive disease (PD), unacceptable toxicity or patient withdrawal
Other RET-altered solid tumours (prior 1st gen SRI)	EP0031	EP0031 capsules at the recommended phII dose, taken once daily until progressive disease (PD), unacceptable toxicity or patient withdrawal
RET fusion-positive NSCLC (no prior SRI therapy)	EP0031	EP0031 capsules at the recommended phII dose, taken once daily until progressive disease (PD), unacceptable toxicity or patient withdrawal
Other RET-altered solid tumours (no prior SRI therapy)	EP0031	EP0031 capsules at the recommended phII dose, taken once daily until progressive disease (PD), unacceptable toxicity or patient withdrawal
RET fusion-positive NSCLC (prior 1st gen SRI)	EP0031	EP0031 capsules at the recommended phII dose, taken once daily until progressive disease (PD), unacceptable toxicity or patient withdrawal
RET mutation-positive MTC (no prior SRI therapy)	EP0031	EP0031 capsules at the recommended phII dose, taken once daily until progressive disease (PD), unacceptable toxicity or patient withdrawal

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
Area under the plasma concentration versus time curve (AUC)	First 48 hours after drug administered	To characterise the pharmacokinetics (PK) of EP0031
Maximum Plasma Concentration (Cmax)	First 24 hours after drug administered	To characterise the pharmacokinetics (PK) of EP0031
Time taken for drug concentration to fall from half its original value (Half-life)	First 72 hours after drug administered	To characterise the pharmacokinetics (PK) of EP0031

Trial Locations

Locations (34)

David Geffen School of Medicine at UCLA; 🇺🇸 Los Angeles, California, United States

Stanford University; 🇺🇸 Stanford, California, United States

Georgetown University; 🇺🇸 Washington, District of Columbia, United States

Florida Cancer Specialist; 🇺🇸 Fort Myers, Florida, United States

RUSH University Medical Center; 🇺🇸 Chicago, Illinois, United States

Northwestern University; 🇺🇸 Evanston, Illinois, United States

University of Kentucky; 🇺🇸 Lexington, Kentucky, United States

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

Karmanos; 🇺🇸 Detroit, Michigan, United States

Memorial Sloan Kettering Cancer Center; 🇺🇸 New York, New York, United States

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