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

• Sponsor: Ellipses Pharma (Industry)
• Overall Status: Not yet recruiting
• CT.gov ID: NCT05443126
• Collaborator: (none)
• Enrollment: 265
• Location: 1
• Arms: 6
• Anticipated Duration (Months): 57
• Patients Per Site Per Month: 4.7

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Advanced Solid Tumor	Drug: EP0031	Phase 1/Phase 2

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 Design

• Study Type: Interventional
• Anticipated Enrollment: 265 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Anticipated Study Start Date: Sep 1, 2022
• Anticipated Primary Completion Date: Dec 1, 2026
• Anticipated Study Completion Date: Jun 1, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: RET fusion-positive NSCLC EP0031 capsules at the recommended phII dose, taken once daily until progressive disease (PD), unacceptable toxicity or patient withdrawal	Drug: EP0031; EP0031 is a potent next-generation selective RET-inhibitor (SRI)
Experimental: RET mutation-positive MTC EP0031 capsules at the recommended phII dose, taken once daily until progressive disease (PD), unacceptable toxicity or patient withdrawal	Drug: EP0031; EP0031 is a potent next-generation selective RET-inhibitor (SRI)
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	Drug: EP0031; EP0031 is a potent next-generation selective RET-inhibitor (SRI)
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	Drug: EP0031; EP0031 is a potent next-generation selective RET-inhibitor (SRI)
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	Drug: EP0031; EP0031 is a potent next-generation selective RET-inhibitor (SRI)
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	Drug: EP0031; EP0031 is a potent next-generation selective RET-inhibitor (SRI)

Outcome Measures

Primary Outcome Measures

1. Module A: Incidence of Dose-limiting Toxicity (DLTs ) during the first 28 days of EP0031 treatment [First 28 days of treatment]

2. Modules B and C: Overall Response Rate (ORR) as measured using RECIST v1.1 [12 months]

Secondary Outcome Measures

1. Area under the plasma concentration versus time curve (AUC) [First 48 hours after drug administered]

   To characterise the pharmacokinetics (PK) of EP0031

2. Maximum Plasma Concentration (Cmax) [First 24 hours after drug administered]

   To characterise the pharmacokinetics (PK) of EP0031

3. 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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	David Geffen School of Medicine at UCLA	Los Angeles	California	United States	90095

Sponsors and Collaborators

• Ellipses Pharma

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Ellipses Pharma
• ClinicalTrials.gov Identifier: NCT05443126
• Other Study ID Numbers: EP0031-101
• First Posted: Jul 5, 2022
• Last Update Posted: Jul 5, 2022
• Last Verified: Jul 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Ellipses Pharma: selective RET-inhibitor
• Additional relevant MeSH terms: Neoplasms

Study Results

No Results Posted as of Jul 5, 2022