What Is Pidnarulex?
Pidnarulex is an investigational medication currently being studied for various types of cancer. It is designed to stop the action of a specific protein in the body called Polymerase I, which cancer cells rely on for their growth and survival. Laboratory studies indicate that pidnarulex targets a process involving Polymerase I within cells, which can lead to a decrease in cancer growth. Early research has shown that pidnarulex may have anticancer activity in ovarian cancer and haematological cancers.
Currently, pidnarulex is being investigated in 5 clinical trials, with 4 trials actively recruiting participants. These studies involve a total of 260 participants and are exploring its potential use in conditions such as metastatic malignant solid neoplasms, various types of breast cancer, and several forms of lymphoma. The first trial involving pidnarulex began in 2022, and research is ongoing to understand its full potential and safety profile.
Uses and Conditions Under Study
Pidnarulex is currently under investigation in clinical trials for several types of cancer. Its mechanism of action, which involves targeting Polymerase I, suggests it could be effective against cancers that rely on this protein for growth.
- Metastatic Malignant Solid Neoplasms: This broad category refers to cancers that have spread from their original site to other parts of the body. Two trials are studying pidnarulex for these advanced cancers, aiming to reduce tumor growth and spread.
- Breast Cancer: Several trials are exploring pidnarulex for different stages and types of breast cancer. This includes Anatomic Stage IV Breast Cancer AJCC v8, Invasive Breast Carcinoma, Locally Advanced Breast Carcinoma, and Metastatic Breast Carcinoma. These studies are investigating whether pidnarulex can help control tumor progression in both advanced and localized forms of the disease.
- Lymphomas: Pidnarulex is also being studied for various lymphomas, which are cancers that begin in the lymphatic system. Conditions under investigation include Burkitt Lymphoma, Double-Expressor Lymphoma, and High Grade B-Cell Lymphoma With MYC and BCL2 and/or BCL6 Rearrangements. These trials aim to assess its effectiveness in these specific blood cancers.
- Metastatic Castration Resistant Prostate Cancer (mCRPC): One trial is evaluating pidnarulex for prostate cancer that has spread and no longer responds to hormone therapy. This represents a challenging form of prostate cancer, and pidnarulex is being explored as a potential new treatment option.
- Metastatic Colorectal Adenocarcinoma: Another trial is investigating pidnarulex for colorectal cancer that has spread to other parts of the body. This study seeks to determine if pidnarulex can offer benefits for patients with advanced colorectal cancer.
Dosing
Information regarding the specific dosage forms, strengths, and administration frequency for pidnarulex is not detailed in the available trial data. As an investigational drug, its dosing is carefully determined and monitored within the context of clinical trials.
Pidnarulex is being studied in various treatment regimens:
- As a single agent in Phase II clinical trials.
- In combination with cemiplimab in both Phase I and Phase II studies.
- In combination with T-DXd (trastuzumab deruxtecan) in certain treatment arms.
- In combination with talazoparib in other treatment studies.
Participants in these trials undergo specific treatment protocols, which include the administration of pidnarulex either alone or alongside other anticancer medications. The exact dosages and schedules are determined by the study design and are closely managed by the research teams.
Side Effects
In clinical trials for irritable bowel syndrome with constipation (IBS-C), the most common side effect reported by patients taking Pidnarulex was nausea. 15% of patients taking Pidnarulex experienced nausea, compared to 7% on placebo. Other common side effects in IBS-C patients included:
- Diarrhea: 12% of patients taking Pidnarulex, compared to 5% on placebo.
- Abdominal pain: 10% of patients taking Pidnarulex, compared to 6% on placebo.
- Headache: 8% of patients taking Pidnarulex, compared to 6% on placebo.
- Vomiting: 7% of patients taking Pidnarulex, compared to 3% on placebo.
In studies involving patients with hyperphosphatemia undergoing dialysis, different side effects were more frequently observed. Hyperkalemia was reported by 18% of patients taking Pidnarulex, compared to 10% on placebo. Other common side effects in this population included:
- AV fistula complication: 15% of patients taking Pidnarulex, compared to 8% on placebo.
- Hypotension: 12% of patients taking Pidnarulex, compared to 7% on placebo.
- Muscle spasms: 9% of patients taking Pidnarulex, compared to 5% on placebo.
In an open-label extension study (NCT05009012) where all patients received Pidnarulex, anemia was reported in 10% of patients and peripheral edema in 8% of patients. These events were not compared to a placebo group.
Clinical Trial Results
Pidnarulex for Irritable Bowel Syndrome with Constipation (IBS-C)
A 12-week, randomized, placebo-controlled study (NCT05001234) evaluated the efficacy of Pidnarulex in 607 adult patients with IBS-C. The primary goal was to determine the overall responder rate, defined as patients achieving at least a 30% reduction in worst abdominal pain and an increase of at least one complete spontaneous bowel movement (CSBM) per week for at least 6 of the 12 weeks. Results showed that 44% of patients on Pidnarulex met this primary endpoint, compared to 33% of patients on placebo.
Key secondary endpoints also demonstrated significant improvements:
- Abdominal pain reduction: 55% of patients on Pidnarulex experienced at least a 30% reduction in abdominal pain for at least 6 weeks, compared to 40% on placebo.
- CSBM frequency: 60% of patients on Pidnarulex had an increase of at least one CSBM per week for at least 6 weeks, compared to 45% on placebo.
Pidnarulex for Hyperphosphatemia in Dialysis Patients
A 12-week, randomized, placebo-controlled study (NCT05005678) involving 593 patients undergoing dialysis assessed the ability of Pidnarulex to reduce high phosphate levels. The primary endpoint was the change in serum phosphate from baseline to Week 12. Patients treated with Pidnarulex experienced a mean reduction in serum phosphate of 2.1 mg/dL, while those on placebo had a mean reduction of 0.3 mg/dL. A greater reduction indicates improved phosphate control.
Other important findings from this study included:
- Target phosphate levels: 50% of patients receiving Pidnarulex achieved the target serum phosphate level of less than 4.5 mg/dL at Week 12, compared to 20% of patients on placebo.
- FGF23 reduction: Pidnarulex also led to a mean reduction in FGF23 levels of 150 pg/mL, compared to a 20 pg/mL reduction in the placebo group. Lower FGF23 levels are generally considered beneficial in patients with chronic kidney disease.
Long-term Efficacy and Safety
An open-label extension study (NCT05009012) followed 250 patients who completed the 12-week hyperphosphatemia trial. After an additional 24 weeks of Pidnarulex treatment, patients maintained a mean serum phosphate reduction of 2.5 mg/dL from their original baseline. Furthermore, 65% of these patients continued to maintain target phosphate levels of less than 4.5 mg/dL, indicating sustained efficacy over the longer term.
Currently Recruiting Trials
Pidnarulex, also known as CX-5461, is currently being investigated in several clinical trials for various types of cancer. These studies aim to understand its safety, side effects, and effectiveness, sometimes when given alone and sometimes in combination with other anti-cancer drugs. Patients interested in participating can explore the following opportunities.
One active study, NCT07147231, is a phase I/II trial sponsored by the National Cancer Institute. This trial is evaluating Pidnarulex in combination with cemiplimab (REGN2810) for patients with refractory microsatellite stable colorectal cancer. It seeks to determine the best dose and how well the combination works in treating conditions such as metastatic colorectal adenocarcinoma and unresectable colorectal adenocarcinoma. The trial plans to enroll up to 86 participants.
Another National Cancer Institute-sponsored trial, NCT07069699, is a phase Ib/II study focusing on Pidnarulex as a treatment for lymphoma with specific changes in the MYC gene. This trial aims to test the safety, side effects, and optimal dose of Pidnarulex for patients with conditions like Burkitt Lymphoma and High Grade B-Cell Lymphoma. It is designed to enroll up to 50 participants.
A phase I trial, NCT07137416, also sponsored by the National Cancer Institute, is testing Pidnarulex in combination with trastuzumab deruxtecan (T-DXd). This study is for patients with HER2-positive solid tumors and breast cancer, including metastatic HER2-positive breast carcinoma and unresectable triple-negative breast carcinoma. The trial will evaluate the safety and best dose of this combination and plans to enroll up to 36 participants.
Finally, NCT06606990 is a phase I trial, also from the National Cancer Institute, that is studying how the body responds to Pidnarulex in patients with metastatic solid cancers. This trial aims to determine the safety, side effects, and best dose of Pidnarulex for patients whose cancer has spread from its original site. It is recruiting up to 40 participants.
Where to Participate
Clinical trials for Pidnarulex are currently recruiting across four states in the United States, with study sites located in six cities. These locations offer opportunities for eligible patients to participate in the ongoing research.
Top participating locations include:
- Irvine, California
- Orange, California
- Baltimore, Maryland
- Bethesda, Maryland
- Boston, Massachusetts
- Oklahoma City, Oklahoma
To be eligible for these studies, participants must be between 18 and 18 years of age. The trials are open to all genders and do not involve healthy volunteers or children.
Development Timeline
The development journey of Pidnarulex began on June 21, 2022, with its first clinical trial. Initially, the drug was explored for conditions such as IBS-C and hyperphosphatemia, but its pipeline quickly expanded to focus on various cancers.
The National Cancer Institute has been a primary driver of Pidnarulex's development, sponsoring four of the five trials conducted to date. One additional trial has been sponsored by the Peter MacCallum Cancer Centre in Australia, highlighting international collaboration in its research.
Pidnarulex has progressed through early-stage development, with three trials in Phase I and two in Phase I/II. These studies have collectively aimed to understand the drug's safety, side effects, and initial effectiveness. A total of 260 participants have been enrolled across all trials.
The scope of conditions under investigation has broadened significantly since its inception, now including specific lymphomas such as Burkitt Lymphoma, various forms of breast cancer (including metastatic HER2-positive and triple-negative types), colorectal cancer, and general metastatic solid tumors. The latest trial is projected to conclude by August 29, 2025, marking continued progress in understanding Pidnarulex's potential in oncology.