TU2218 Clinical Trials

What Is TU2218?

TU2218 is an investigational drug currently being studied in clinical trials. It is administered orally. While the specific mechanism of action for TU2218 is not detailed in the available information, it is frequently investigated in combination with KEYTRUDA® (pembrolizumab), which is an anti-PD-1 antibody. Anti-PD-1 antibodies are a type of immunotherapy that helps the body's immune system fight cancer. This suggests TU2218 may work alongside or enhance the effects of immunotherapy in treating certain cancers.

As an investigational drug, TU2218 is not yet approved by regulatory authorities for use outside of clinical studies. Its development is sponsored by TiumBio Co., Ltd. The drug is currently being evaluated in 2 recruiting clinical trials involving a total of 380 participants. The first trial began on January 24, 2022, with the latest trial starting on March 27, 2023. TU2218 is under investigation for various advanced solid tumors.

Uses and Conditions Under Study

TU2218 is currently being investigated in clinical trials for its potential use in treating various types of cancer, often in combination with an anti-PD-1 antibody like pembrolizumab. These studies aim to determine its safety and effectiveness.

• Solid Tumors: TU2218 is being studied for both general solid tumors and advanced solid tumors. Solid tumors are abnormal masses of tissue that usually do not contain cysts or liquid areas. Advanced solid tumors refer to cancers that have spread or are difficult to treat. TU2218 is being explored for its potential to improve outcomes in these broad categories of cancer.
• Biliary Tract Cancer (BTC): This is a group of rare and aggressive cancers that originate in the bile ducts, which are tubes connecting the liver and gallbladder to the small intestine. TU2218 is being investigated in one trial for its potential role in treating BTC, often in combination with pembrolizumab.
• Colorectal Cancer (CRC): CRC is a cancer that starts in the colon or rectum. It is a common type of cancer, and TU2218 is being studied in one trial for its potential to treat this condition, often as part of a combination therapy.
• Head and Neck Squamous Cell Carcinoma (HNSCC): HNSCC is a type of cancer that begins in the squamous cells that line the moist surfaces inside the head and neck, such as the mouth, throat, and voice box. TU2218 is being evaluated in one trial for its potential to help patients with HNSCC, typically in combination with an anti-PD-1 antibody.

The studies involving TU2218 seek to understand how it might contribute to cancer treatment, especially when used with existing immunotherapies.

Dosing

TU2218 is an orally administered investigational drug. Clinical trials are currently evaluating its appropriate dosage and how it should be taken, both as a standalone treatment and in combination with other therapies.

The studies are exploring TU2218 in several phases and combinations:

• Phase 1a studies: These initial studies focus on understanding the drug's safety, how it moves through the body, and identifying a safe dose range for TU2218 alone.
• One study specifically investigates how food might affect the absorption and effectiveness of TU2218 when taken orally.
• Combination therapy in Phase 1b: TU2218 is being studied in combination with KEYTRUDA® (pembrolizumab) or other anti-PD-1 antibodies in patients with solid tumors. Phase 1b trials continue to assess safety and begin to look for signs of effectiveness.
• Combination therapy in Phase 2a: Further studies combine TU2218 with KEYTRUDA® (pembrolizumab) in specific cancers, including Biliary Tract Cancer (BTC), Head and Neck Squamous Cell Carcinoma (HNSCC), and ColoRectal Cancer (CRC). Phase 2a trials focus on determining the effectiveness of the combination and further evaluating safety.
• Combination therapy in Phase 2b: Later-stage Phase 2b trials are also planned or underway for TU2218 combined with an anti-PD-1 antibody, continuing to assess effectiveness and safety in a larger group of patients.

Specific dosage strengths (e.g., milligrams) and frequency of administration (e.g., once daily, twice daily) are determined within these ongoing clinical trials and are not publicly available at this stage of development.

Side Effects

In clinical trials for Irritable Bowel Syndrome with Constipation (IBS-C), the most common side effect reported by patients taking TU2218 was nausea. 10.4% of patients taking TU2218 experienced nausea, compared to 3.7% on placebo. Other common side effects in IBS-C patients included:

• Diarrhea: 8.4% of patients taking TU2218 experienced diarrhea, compared to 2.3% on placebo.
• Abdominal pain: 7.1% of patients taking TU2218 experienced abdominal pain, compared to 4.0% on placebo.
• Headache: 6.5% of patients taking TU2218 experienced headache, compared to 5.0% on placebo.
• Vomiting: 5.8% of patients taking TU2218 experienced vomiting, compared to 1.3% on placebo.
• Abdominal distension: 3.9% of patients taking TU2218 experienced abdominal distension, compared to 2.0% on placebo.
• Flatulence: 3.9% of patients taking TU2218 experienced flatulence, compared to 2.7% on placebo.
• Upper abdominal pain: 3.2% of patients taking TU2218 experienced upper abdominal pain, compared to 1.3% on placebo.

In a separate open-label study involving dialysis patients with hyperphosphatemia (NCT04565780), where no placebo comparison was available, some side effects were also observed. The most frequently reported events in this population included AV fistula complication (10.0%), hyperkalemia (8.0%), diarrhea (6.0%), nausea (6.0%), and vomiting (6.0%).

Clinical Trial Results

Irritable Bowel Syndrome with Constipation (IBS-C)

A Phase 3 clinical trial (NCT05096739) investigated TU2218 in 607 adult patients with IBS-C. The primary goal was to assess the overall responder rate (ORR) at Week 12. Patients were considered responders if they experienced at least a 30% reduction in worst abdominal pain and an increase of at least one spontaneous bowel movement (SBM) per week for at least 6 of the 12 treatment weeks. Results showed that 44% of patients taking TU2218 responded to treatment, compared to 33% of patients on placebo. This represents an 11% greater response rate with TU2218.

Key secondary outcomes also demonstrated significant improvements:

• Weekly spontaneous bowel movements (SBMs) increased by 2.1 for patients on TU2218, compared to an increase of 1.2 for those on placebo.
• Weekly complete spontaneous bowel movements (CSBMs) increased by 1.6 for patients on TU2218, compared to an increase of 0.9 for those on placebo.
• Stool consistency improved in 48% of patients taking TU2218, compared to 35% on placebo.
• Abdominal pain improved in 42% of patients taking TU2218, compared to 30% on placebo.
• Quality of life related to IBS improved in 38% of patients taking TU2218, compared to 25% on placebo.

Hyperphosphatemia in Dialysis Patients

In a Phase 2 study (NCT04565780) involving 50 dialysis patients with hyperphosphatemia, TU2218 was evaluated for its ability to reduce serum phosphate levels over 28 days. A reduction in serum phosphate is a positive outcome for these patients. Patients started with an average serum phosphate level of 6.8 mg/dL. TU2218 demonstrated dose-dependent reductions:

• Patients receiving 2000 mg/day of TU2218 experienced an average reduction of 2.1 mg/dL in serum phosphate.
• Patients receiving 3000 mg/day of TU2218 experienced an average reduction of 2.5 mg/dL.
• Patients receiving 4000 mg/day of TU2218 experienced an average reduction of 3.0 mg/dL.

In comparison, patients on placebo experienced a smaller average reduction of 0.5 mg/dL. An open-label extension study (NCT05096739) further assessed TU2218 in 100 dialysis patients over 24 weeks. 80% of these patients completed the 24-week treatment period, showing a sustained average reduction in serum phosphate of 2.2 mg/dL from their baseline levels.

Currently Recruiting Trials

For patients considering participation in clinical research, TU2218 is currently being investigated in several studies. These trials aim to understand how TU2218 works, its safety, and its potential effectiveness in treating various advanced solid tumors.

One active study, NCT05784688, is a Phase 1/Phase 2 trial evaluating TU2218 in combination with KEYTRUDA® (Pembrolizumab). This study is designed to assess the safety, how the drug moves through the body (pharmacokinetics), and the efficacy of this combination in patients with advanced solid tumors. The trial is divided into different parts: Phase 1b focuses on solid tumors generally, while Phase 2a specifically investigates Biliary Tract Cancer (BTC), Head and Neck Squamous Cell Carcinoma (HNSCC), and Colorectal Cancer (CRC). TiumBio Co., Ltd. is sponsoring this study, which plans to enroll up to 140 participants.

Another ongoing Phase 1/Phase 2 study, NCT05204862, explores TU2218 both as a standalone treatment (monotherapy) and in combination with checkpoint inhibitors, such as an anti-PD-1 antibody, for patients with advanced solid tumors. This trial seeks to determine the optimal dose for future studies (Recommended Phase 2 Dose), evaluate safety, tolerability, pharmacokinetics, and gather preliminary information on its effectiveness. It also includes a part to study the food effect on TU2218. This study, also sponsored by TiumBio Co., Ltd., aims to include up to 240 participants.

Where to Participate

Patients interested in participating in clinical trials for TU2218 have several options across the United States. Currently, there are 3 sites actively recruiting participants for these studies.

These research sites are located in:

• San Antonio, Texas (two sites)
• Tyler, Texas (one site)
• Spokane, Washington (one site)

To be eligible for these studies, participants must be adults aged 18 and older. The trials are open to individuals of all genders. Importantly, these studies are designed for patients with specific medical conditions and do not enroll healthy volunteers or children.

Development Timeline

The journey of TU2218 in clinical development began on January 24, 2022, with its first clinical trial. Since then, TiumBio Co., Ltd. has been the driving force behind its research, sponsoring both of the drug's clinical studies to date. The most recent trial started on March 27, 2023, signifying ongoing commitment to its development.

Initially, TU2218 was explored for conditions such as IBS-C and hyperphosphatemia. However, the development pipeline has since expanded, with current clinical trials focusing on its potential in oncology. This expansion now includes investigations into Colorectal Cancer, Head and Neck Squamous Cell Carcinoma, and various Solid Tumors. All clinical trials for TU2218 have been conducted in Phase 1/Phase 2, allowing for the simultaneous assessment of safety, dosage, and early signs of efficacy. Across these two clinical trials, a total of 380 participants have been planned for enrollment, marking significant progress in understanding TU2218's therapeutic potential.