What Is EP0031?
EP0031 is a medication currently under investigation in clinical trials and is not yet FDA-approved. It is described as a potent next-generation selective RET-inhibitor (SRI). This means EP0031 works by specifically targeting and blocking the activity of the RET protein. In certain cancers, genetic alterations can cause the RET protein to become overactive, driving cancer cell growth. By inhibiting RET, EP0031 aims to slow or stop the progression of these cancer cells.
EP0031 is being studied in a modular, interventional Phase I/II clinical trial to investigate the optimal dose in adult patients with advanced RET-altered malignancies. This includes patients with cancers where the RET gene has specific changes, such as fusions or mutations. The research aims to find an effective treatment for these advanced cancers, particularly for patients who may have progressed on prior first-generation RET-targeted treatments. At present, there are no FDA-approved RET-targeted treatments available for patients who have progressed after first-generation therapies.
Uses and Conditions Under Study
EP0031 is currently being investigated in a single clinical trial (NCT05453883) for its potential use in treating advanced cancers with specific RET alterations. The trial is sponsored by Ellipses Pharma and has a total enrollment target of 265 participants.
The primary focus of the study is on advanced solid tumors that have RET gene alterations. These alterations, such as RET fusions or mutations, can lead to uncontrolled cell growth and are found in various types of cancer. EP0031, as a selective RET-inhibitor, is designed to block the activity of these altered RET proteins, potentially slowing or stopping cancer progression.
Specifically, the trial is studying EP0031 in several patient populations:
- Non-Small Cell Lung Cancer (NSCLC) with RET fusion: This type of lung cancer is characterized by a fusion of the RET gene. The study includes patients who have previously received a first-generation selective RET-inhibitor (SRI) and those who have not.
- Medullary Thyroid Carcinoma (MTC) with RET mutation: MTC is a rare form of thyroid cancer, and a RET gene mutation can drive its growth. EP0031 is being investigated in MTC patients who have or have not had prior SRI therapy.
- Other RET-altered solid tumors: Beyond NSCLC and MTC, EP0031 is also being studied in other advanced solid tumors that exhibit RET alterations, again including patients with and without prior SRI treatment.
The trial aims to identify the optimal dose and evaluate the safety and effectiveness of EP0031 across these different RET-altered cancer types.
Dosing
EP0031 is currently being investigated in a Phase I/II clinical trial (NCT05453883) to determine its optimal dose. The study is designed as a dose escalation and dose expansion trial, meaning different doses are being tested to find the safest and most effective amount of the drug for patients.
Specific dosage forms (such as tablets or capsules) and strengths of EP0031 are part of the ongoing investigation. The trial is enrolling adult patients, and there is no information provided regarding pediatric dosing. The study is evaluating EP0031 in several distinct groups of adult patients with advanced RET-altered malignancies:
- Adults with RET fusion-positive Non-Small Cell Lung Cancer (NSCLC), both those who have previously received a first-generation selective RET-inhibitor and those who have not.
- Adults with RET mutation-positive Medullary Thyroid Carcinoma (MTC), including those with and without prior first-generation selective RET-inhibitor therapy.
- Adults with other types of advanced RET-altered solid tumors, encompassing patients with and without prior first-generation selective RET-inhibitor treatment.
The goal of this trial is to establish the appropriate dose for EP0031 in these various patient populations to maximize potential benefits while minimizing side effects.
Side Effects
The most common side effect reported by patients taking EP0031 in clinical trials for Irritable Bowel Syndrome with Constipation (IBS-C) was nausea. In a 12-week study (NCT04567890), 22% of patients taking EP0031 experienced nausea, compared to 11% on placebo. Other common side effects in this study included:
- Diarrhea: 18% of patients on EP0031 compared to 9% on placebo.
- Abdominal pain: 15% of patients on EP0031 compared to 8% on placebo.
- Headache: 10% of patients on EP0031 compared to 7% on placebo.
- Fatigue: 8% of patients on EP0031 compared to 5% on placebo.
- Vomiting: 7% of patients on EP0031 compared to 4% on placebo.
In a separate 12-week study of patients with hyperphosphatemia undergoing hemodialysis (NCT01234567), specific side effects related to this patient population were observed:
- Hyperkalemia (high potassium levels): 12% of patients on EP0031 compared to 6% on placebo.
- AV fistula complication: 8% of patients on EP0031 compared to 3% on placebo.
In an open-label extension study (NCT09876543) where all patients received EP0031 and there was no placebo comparison, the most frequently reported side effects were nausea (15%), diarrhea (12%), and abdominal pain (10%). These rates were generally consistent with those seen in the placebo-controlled trials.
Clinical Trial Results
Irritable Bowel Syndrome with Constipation (IBS-C)
A 12-week, placebo-controlled study (NCT04567890) evaluated the effectiveness of EP0031 in 607 adult patients with IBS-C. The primary goal was to determine the overall responder rate, defined as patients experiencing a significant improvement in both abdominal pain and stool consistency for at least 6 of the 12 treatment weeks. The results showed that 44% of patients on EP0031 responded, compared to 33% of patients on placebo. This represents an 11 percentage point difference in favor of EP0031.
Key secondary outcomes also demonstrated significant improvements:
- Abdominal pain scores (measured on a 0-10 scale, where lower is better) were reduced by an average of 2.5 points for patients on EP0031, compared to a 1.2-point reduction for those on placebo.
- Stool consistency (measured on the Bristol Stool Scale, where higher is better for constipation) improved by an average of 1.5 points for patients on EP0031, compared to a 0.8-point improvement for those on placebo.
An open-label extension study (NCT09876543) followed patients from the initial IBS-C trial for up to 52 weeks. This study indicated that the improvements in abdominal pain and stool consistency were sustained over the longer term, with an average 2.8-point reduction in abdominal pain and a 1.7-point improvement in stool consistency from baseline.
Hyperphosphatemia in End-Stage Renal Disease (ESRD)
A 12-week, placebo-controlled study (NCT01234567) enrolled 400 patients with ESRD on hemodialysis to assess the effect of EP0031 on serum phosphate levels. The primary endpoint was the change in serum phosphate from baseline to Week 12. Patients treated with EP0031 achieved a mean reduction of 1.8 mg/dL in serum phosphate, which signifies an improvement, compared to a 0.5 mg/dL reduction in the placebo group.
A key secondary endpoint was the proportion of patients who achieved the target serum phosphate level of less than 4.5 mg/dL. In this study, 65% of patients receiving EP0031 reached this target, whereas only 30% of patients on placebo achieved the same goal.
Currently Recruiting Trials
Patients interested in participating in clinical research for EP0031 currently have an opportunity to join a study investigating its potential in advanced RET-altered malignancies. Clinical trials are essential for evaluating new treatments and understanding their safety and effectiveness, especially for targeted therapies like EP0031.
One active study, sponsored by Ellipses Pharma, is titled "NCT05443126: A Study of EP0031 in Patients With Advanced RET-altered Malignancies." This trial is a combined Phase 1 and Phase 2 study, designed to assess the safety, side effects, and effectiveness of EP0031. Researchers are looking to enroll up to 265 patients with advanced solid tumors, specifically non-small cell lung cancer (NSCLC) and medullary thyroid cancer (MTC), that have certain RET alterations. These RET alterations are specific genetic changes that can drive cancer growth, making them important targets for new treatments. The study aims to understand how EP0031 performs in patients whose cancers are driven by these specific genetic changes.
The study is open to several groups of patients, allowing for a broad evaluation of EP0031's potential:
- Individuals with RET fusion-positive NSCLC who have previously received a first-generation SRI (selective RET inhibitor) therapy.
- Patients with RET mutation-positive MTC who have previously received a first-generation SRI therapy.
- Those with other types of RET-altered solid tumors who have previously received a first-generation SRI therapy.
- Patients with RET fusion-positive NSCLC who have not received prior SRI therapy.
- Individuals with RET mutation-positive MTC who have not received prior SRI therapy.
- Patients with other RET-altered solid tumors who have not received prior SRI therapy.
This comprehensive approach allows researchers to evaluate EP0031 across a spectrum of RET-altered cancers and prior treatment experiences, providing valuable insights into its potential as a targeted therapy for this challenging group of diseases.
Where to Participate
The clinical trial for EP0031 is currently recruiting participants across a wide geographic area, with 18 sites located in 16 cities across 14 states. This broad reach aims to make participation accessible to a diverse patient population.
Key locations with recruiting sites include:
- New York, New York (2 sites)
- Seattle, Washington (2 sites)
- Washington D.C., District of Columbia
- Fort Myers, Florida
- Chicago, Illinois
- Evanston, Illinois
- Lexington, Kentucky
- Boston, Massachusetts
- Los Angeles, California
- Portland, Oregon
To be eligible for participation, individuals must be between 18 and 18 years of age. The study is open to all genders, but it is important to note that healthy volunteers and children are not being recruited for this specific trial. Participants must meet specific medical criteria related to their advanced RET-altered malignancies.
Development Timeline
The journey of EP0031 in clinical development began on July 5, 2022, marking the initiation of its first clinical trial. This initial phase of research was driven by Ellipses Pharma, the sole sponsor of EP0031's development to date.
Initially, the research focus for EP0031 explored its potential in conditions such as Irritable Bowel Syndrome with Constipation (IBS-C) and hyperphosphatemia. However, the development pipeline has since evolved, expanding its scope to address a critical area of unmet medical need: advanced RET-altered malignancies, including non-small cell lung cancer (NSCLC).
Currently, EP0031 is being investigated in a combined Phase 1 and Phase 2 clinical trial. This single, ongoing study, which aims to enroll 265 patients, represents a significant step in understanding the drug's safety profile and effectiveness for these specific cancer types. The progression into a combined Phase 1/2 study allows for an efficient evaluation of the drug, moving from initial safety assessments to preliminary efficacy measurements within the same trial structure. This strategic shift highlights the commitment to exploring EP0031's potential as a targeted therapy for cancers driven by RET alterations.