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

• ClinicalTrials.gov Identifier: NCT05443126
• Recruitment Status: Recruiting
• First Posted: July 5, 2022
• Last Update Posted: April 19, 2024
• Sponsor: Ellipses Pharma
• Information provided by (Responsible Party): Ellipses Pharma

Tracking Information

• First Submitted Date: June 24, 2022
• First Posted Date: July 5, 2022
• Last Update Posted Date: April 19, 2024
• Actual Study Start Date: September 30, 2022
• Estimated Primary Completion Date: December 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 1, 2022)

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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: July 1, 2022)

• Area under the plasma concentration versus time curve (AUC) [ Time Frame: First 48 hours after drug administered ]
  To characterise the pharmacokinetics (PK) of EP0031
• Maximum Plasma Concentration (Cmax) [ Time Frame: 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) [ Time Frame: First 72 hours after drug administered ]
  To characterise the pharmacokinetics (PK) of EP0031

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of EP0031 in Patients With Advanced RET-altered Malignancies
• 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
• 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.
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Advanced Solid Tumor

Intervention

Drug: EP0031

EP0031 is a potent next-generation selective RET-inhibitor (SRI)

Study Arms

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

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: July 1, 2022): 265
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: June 2027
• Estimated Primary Completion Date: December 2026 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

Applicable to all patients:

1. Must be ≥18 years of age at the time of informed consent, with documented RET-altered malignancy
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 at screening
4. 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:

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Sonia Serrano; +44 (0)20 3743 0992; sonia@ellipses.life

Contact: Liz Clark; +44 (0)20 3743 0992; Liz@ellipses.life

• Listed Location Countries: Spain, United Kingdom, United States

Administrative Information

• NCT Number: NCT05443126
• Other Study ID Numbers: EP0031-101
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Ellipses Pharma
• Original Responsible Party: Same as current
• Current Study Sponsor: Ellipses Pharma
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Ellipses Pharma
• Verification Date: April 2024