Peposertib Clinical Trials

What Is Peposertib?

Peposertib is an investigational drug currently being studied in clinical trials. It is classified as a DRUG and is under investigation as a potential treatment for various types of cancer. The specific mechanism by which Peposertib works is being explored in these studies. Clinical trials involving Peposertib often include procedures such as tissue biopsies, imaging scans (like CT or PET/CT), and blood sample collections to monitor its effects.

Research into Peposertib began with its first clinical trial on 2016-06-24, and the latest trial started on 2023-05-22. To date, Peposertib has been studied in 14 clinical trials, with 7 trials currently recruiting new participants and 2 trials having been completed. These studies have collectively enrolled a total of 1,101 participants.

Uses and Conditions Under Study

Peposertib is being investigated as a potential treatment for a range of cancers, primarily malignant solid neoplasms. These conditions are characterized by abnormal cell growth that can spread to other parts of the body.

• General Malignant Solid Neoplasms: Peposertib is being studied for various forms of malignant solid neoplasms, including metastatic, unresectable, and advanced types, as well as general advanced solid tumors. These trials aim to assess its effectiveness in treating cancers that have spread, cannot be surgically removed, or are in an advanced stage. A total of 6 trials are investigating Peposertib for these broad categories of solid tumors.
• Squamous Cell Carcinomas: Several trials are focused on specific types of squamous cell carcinoma, which are cancers that begin in squamous cells, often found in the lining of organs. These include advanced laryngeal squamous cell carcinoma, advanced oral cavity squamous cell carcinoma, advanced oropharyngeal squamous cell carcinoma, and clinical stage III HPV-mediated (p16-positive) oropharyngeal carcinoma. Peposertib is being explored as a treatment option for these head and neck cancers, with 4 trials dedicated to these conditions.
• Advanced Renal Cell Carcinoma: This is a type of kidney cancer. One trial is investigating Peposertib as a treatment for advanced renal cell carcinoma.
• Endometrial High Grade Endometrioid Adenocarcinoma: This is a type of uterine cancer. One trial is exploring Peposertib for its potential role in treating this specific gynecological cancer.

Dosing

Peposertib is primarily studied as an oral tablet. Clinical trials have investigated its administration under different conditions, including both fasting and fed states, to understand how food intake might affect its absorption and effectiveness in the body. This helps researchers determine the optimal way for patients to take the medication.

Various strengths of Peposertib have been studied in clinical trials, including doses of 50 mg, 100 mg, 150 mg, and 250 mg. Peposertib is frequently studied in combination with other cancer therapies, such as radiation therapy or other chemotherapeutic agents like capecitabine, temozolomide, and avelumab. Researchers are also exploring different treatment sequences and combinations to find the most effective approaches for patients.

Side Effects

In a study (NCT03770689) of Peposertib combined with capecitabine and radiation therapy in patients with rectal cancer, all participants in the 100 mg, 150 mg, and 250 mg dose groups (6 participants each) experienced treatment-emergent adverse events (TEAEs) and treatment-related TEAEs. The single participant in the 50 mg dose group also experienced these events.

All 6 participants in the 100 mg, 150 mg, and 250 mg dose groups, and the 1 participant in the 50 mg dose group, experienced Grade 3 or higher abnormalities in laboratory test values.

Dose-limiting toxicities (DLTs) were observed in:

• 1 out of 6 participants (16.7%) receiving Peposertib 100 mg.
• 1 out of 6 participants (16.7%) receiving Peposertib 150 mg.
• 3 out of 6 participants (50%) receiving Peposertib 250 mg.

No DLTs were reported for the 50 mg dose group.

No participants across any dose group experienced clinically significant abnormalities in electrocardiogram (ECG) findings or markedly abnormal vital sign measurements.

Clinical Trial Results

Clinical results for Peposertib were evaluated in a study (NCT03770689) involving patients with rectal cancer who received Peposertib in combination with capecitabine and radiation therapy.

Pharmacokinetic measurements showed that Peposertib's apparent terminal half-life ranged from approximately 5 to 6.3 hours across different dose levels. The maximum observed plasma concentration (Cmax) and the area under the plasma concentration-time curve (AUC0-t) generally increased with higher doses of Peposertib. For instance, Cmax ranged from 593 to 653 ng/mL at the 100 mg dose and from 1350 to 1760 ng/mL at the 250 mg dose. Similarly, AUC0-t ranged from 2950 to 3450 h*ng/mL at 100 mg and from 7300 to 9450 h*ng/mL at 250 mg. The time to reach maximum plasma concentration (Tmax) was typically between 1 and 2.5 hours.

Regarding efficacy, the median disease-free survival for all participants was 21.2 months.

Clinical Complete Response (cCR) was observed in 16.7% of participants (1 out of 6) in the 100 mg, 150 mg, and 250 mg Peposertib dose groups. No participants in the 50 mg group achieved a cCR.

A composite outcome of pathological complete response (pCR) or clinical complete response (cCR) was achieved by 16.7% of participants (1 out of 6) in the 100 mg dose group. No participants in the 50 mg, 150 mg, or 250 mg dose groups achieved this composite response.

No participants across any dose group achieved a pathological complete response (pCR).

The Neoadjuvant Rectal (NAR) score, where lower scores indicate a better pathological response, showed mean scores of 9.4 for the 100 mg dose, 13.8 for the 150 mg dose, and 21.2 for the 250 mg dose.

Currently Recruiting Trials

Peposertib is currently being investigated in several clinical trials for various types of cancer. These studies aim to understand its safety, effectiveness, and how it works in combination with other treatments. Patients interested in participating may find a suitable trial among those actively recruiting.

One trial, NCT05687136, is a Phase 1 study sponsored by the National Cancer Institute (NCI). It is testing the safety and optimal dose of Peposertib (M3814) when combined with tuvusertib (M1774) for patients with advanced solid tumors. This trial plans to enroll up to 66 participants.

Another NCI-sponsored Phase 1 trial, NCT05711615, is evaluating Peposertib alongside low-dose liposomal doxorubicin, a common chemotherapy. This study focuses on patients with advanced or unresectable sarcomas, including dedifferentiated liposarcoma, leiomyosarcoma, myxofibrosarcoma, synovial sarcoma, and undifferentiated pleomorphic sarcoma, with an enrollment target of 30 individuals.

Telix Pharmaceuticals is sponsoring NCT05868174, a Phase 1 study combining Peposertib with 177Lu-TLX250. This trial is designed for adult patients with carbonic anhydrase IX-expressing solid tumors, including advanced renal cell carcinoma, and aims to enroll 36 participants.

For patients with locally advanced pancreatic cancer, the NCI is conducting a Phase 1/2 trial, NCT04172532. This study investigates the safety and efficacy of Peposertib (M3814) when added to standard radiation therapy, with an enrollment goal of 92 patients.

The NCI is also leading NCT04071236, a Phase 1/2 study for metastatic castration-resistant prostate cancer. This trial explores Peposertib (M3814) in combination with radium-223 dichloride, and potentially avelumab (an immunotherapy), for patients whose cancer has spread to bones or lymph nodes. The study plans to enroll up to 90 participants.

For individuals newly diagnosed with MGMT unmethylated glioblastoma or gliosarcoma, M.D. Anderson Cancer Center is sponsoring NCT04555577. This Phase 1 trial assesses Peposertib in combination with radiation therapy, followed by temozolomide, with an enrollment target of 29 patients.

Finally, NCT02813135 is a broad Phase 1/2 platform trial for pediatric cancer, sponsored by Gustave Roussy, Cancer Campus, Grand Paris. One of its arms includes Peposertib in combination with avelumab and metronomic temozolomide. The overall trial aims to enroll 472 participants across various treatment arms.

Where to Participate

Clinical trials for Peposertib are accessible across a wide geographical area, with study sites located in 75 facilities across 60 cities and 24 states within the United States. This broad reach aims to make participation convenient for a diverse patient population.

The cities with the highest number of recruiting sites include:

• New York, New York (5 sites)
• Los Angeles, California (4 sites)
• St Louis, Missouri (4 sites)
• Miami, Florida (3 sites)
• Atlanta, Georgia (3 sites)
• Boston, Massachusetts (3 sites)
• Bethesda, Maryland (3 sites)

Eligibility for these trials generally includes individuals aged 18 years and older, of all genders. While most trials do not enroll healthy volunteers, some studies specifically include children, particularly those focused on pediatric cancers.

Development Timeline

The journey of Peposertib in clinical development began on June 24, 2016, with its first clinical trial. Since then, the drug has been investigated in a total of 14 clinical trials, enrolling over 1,100 participants.

Initially, Peposertib was explored for conditions such as IBS-C and hyperphosphatemia. However, its development quickly shifted focus, expanding into a wide array of oncology indications. The National Cancer Institute (NCI) has been a significant driver of this research, sponsoring 9 of the 14 trials. Other key sponsors include Gustave Roussy, M.D. Anderson Cancer Center, and Telix Pharmaceuticals, among others.

The majority of Peposertib's clinical trials are in early phases, with 9 studies classified as Phase 1 and 5 studies as Phase 1/2. This indicates a strong focus on establishing the drug's safety, optimal dosing, and preliminary effectiveness, often in combination with other anti-cancer therapies.

The therapeutic scope of Peposertib has broadened considerably, now encompassing numerous advanced or metastatic solid tumors, including various sarcomas, pancreatic cancer, prostate cancer, glioblastoma, and pediatric cancers. This expansion reflects an ongoing effort to explore Peposertib's potential across a diverse range of challenging malignancies.