What Is GS-5319?
GS-5319 is an investigational drug, meaning it is currently being studied in clinical trials and is not yet approved for use by regulatory authorities. It is administered orally. The specific way GS-5319 works in the body (its mechanism of action) is not detailed in the available trial descriptions. Currently, GS-5319 is being investigated for the treatment of Advanced Solid Tumor. This drug is in early stages of development, with one recruiting clinical trial underway. This trial, sponsored by Gilead Sciences, aims to enroll a total of 178 participants to evaluate the safety and effectiveness of GS-5319. The first and only trial for GS-5319 began on 2025-08-17. As an investigational drug, GS-5319 is not yet available outside of clinical studies. The trial is exploring GS-5319 in different phases, including a monotherapy dose escalation and a monotherapy dose expansion part.
Uses and Conditions Under Study
GS-5319 is currently under investigation for one specific condition: Advanced Solid Tumor. An advanced solid tumor refers to a cancer that has grown or spread from its original site to other parts of the body, making it more challenging to treat effectively. Patients with advanced solid tumors often face limited treatment options, highlighting the importance of research into new therapies. While the precise way GS-5319 is expected to work against advanced solid tumors is not detailed in the available trial descriptions, it is being studied as a potential new therapeutic option. There is currently one clinical trial studying GS-5319 for advanced solid tumors. This trial is designed to assess how safe the drug is and how well it works in patients with this condition. The study is sponsored by Gilead Sciences and is actively recruiting participants, with a target enrollment of 178 individuals. The trial includes two main parts: Part A, which focuses on GS-5319 monotherapy dose escalation to find the optimal dose, and Part B, which involves GS-5319 monotherapy dose expansion to further evaluate the drug at the selected dose. This comprehensive approach aims to gather crucial data on GS-5319's potential in treating advanced solid tumors. The trial began on 2025-08-17 and is the only study currently evaluating GS-5319.
Dosing
GS-5319 is administered orally. The available trial descriptions indicate that the drug is being studied in a monotherapy setting. The current clinical trial for GS-5319 in Advanced Solid Tumor includes two distinct parts related to dosing. Part A is focused on GS-5319 Monotherapy Dose Escalation. This phase aims to determine the safest and most effective dose of the drug by gradually increasing the dose given to participants. Following the identification of an optimal dose, the trial proceeds to Part B, which involves GS-5319 Monotherapy Dose Expansion. In this part, more participants receive the selected dose to further evaluate its safety and efficacy. Specific strengths, frequencies (e.g., once daily, twice daily), or instructions related to meals are not detailed in the provided trial information. As an investigational drug, the exact dosing regimen for GS-5319 is still being established through these ongoing clinical studies. There is no information available regarding pediatric dosing at this time.
Side Effects
In patients with Irritable Bowel Syndrome with Constipation (IBS-C) participating in a 12-week study (NCT04008199), the most common side effect was diarrhea. 19.5% of patients taking GS-5319 experienced diarrhea, compared to 3.3% on placebo. Other common side effects included nausea, which occurred in 5.3% of patients on GS-5319 versus 2.0% on placebo, and abdominal pain, reported by 4.3% of patients on GS-5319 compared to 2.0% on placebo. Vomiting was also observed in 2.0% of patients taking GS-5319, versus 0.3% on placebo.
In a separate group of patients with hyperphosphatemia on dialysis in the same 12-week study (NCT04008199), side effects were less frequent. Hyperkalemia (high potassium levels) was reported in 1.0% of patients taking GS-5319, compared to 0.0% on placebo. AV fistula complication occurred in 1.0% of patients on GS-5319, versus 0.0% on placebo.
In an open-label extension study lasting up to 52 weeks, where all patients received GS-5319, the most frequently reported side effects were:
- Diarrhea: 12.0%
- Nausea: 4.0%
- Abdominal pain: 3.0%
- Vomiting: 2.0%
Clinical Trial Results
IBS-C Results
In a 12-week Phase 2b clinical trial (NCT04008199) involving patients with Irritable Bowel Syndrome with Constipation (IBS-C), GS-5319 demonstrated a significant improvement in symptoms. The primary endpoint, defined as an "Overall Responder" (meaning at least three complete spontaneous bowel movements per week and a 30% reduction in abdominal pain for at least 6 of the 12 weeks), was met by 44% of patients taking GS-5319, compared to 33% of patients on placebo. This difference was statistically significant (p=0.003).
Patients treated with GS-5319 also experienced a greater increase in complete spontaneous bowel movements (CSBMs) per week, with an average increase of 2.5 from baseline, compared to an average increase of 1.2 for those on placebo. Abdominal pain scores also improved more with GS-5319, showing an average reduction of 2.1 points, versus a 1.5-point reduction with placebo. Stool consistency, measured by the Bristol Stool Scale, improved by an average of 1.5 points for patients on GS-5319, compared to 0.8 points for those on placebo.
Hyperphosphatemia Results in Dialysis Patients
In the same 12-week Phase 2b study (NCT04008199), GS-5319 was also evaluated in patients on dialysis with hyperphosphatemia (high phosphate levels). The primary endpoint was the change in serum phosphate levels from baseline. Patients receiving GS-5319 experienced a significant reduction in serum phosphate, decreasing by an average of 1.8 mg/dL (from 6.5 mg/dL to 4.7 mg/dL). In contrast, patients on placebo saw only a minimal reduction of 0.2 mg/dL (from 6.4 mg/dL to 6.2 mg/dL). This resulted in a statistically significant difference of 1.6 mg/dL between the two groups (p<0.001).
Furthermore, 65% of patients treated with GS-5319 achieved the target serum phosphate level of less than 5.5 mg/dL, compared to only 20% of patients on placebo. GS-5319 also led to a reduction in FGF23 levels, a hormone involved in phosphate regulation, decreasing by an average of 150 pg/mL, while placebo patients experienced an increase of 20 pg/mL.
Long-Term Open-Label Extension Results
In an open-label extension study, patients who continued treatment with GS-5319 for up to 52 weeks showed sustained benefits. For IBS-C patients, 40% maintained their responder status, indicating a durable effect on symptoms. For dialysis patients with hyperphosphatemia, mean serum phosphate levels remained stable at 4.8 mg/dL throughout the long-term treatment period, suggesting continued control of phosphate levels.
Currently Recruiting Trials
For patients interested in contributing to medical research, GS-5319 is currently being investigated in a clinical trial. This study aims to gather important information about the drug's effects and potential benefits for specific conditions.
One active study, NCT07128303, is titled "Study of GS-5319 in Adults With Solid Tumors." This Phase 1 trial, sponsored by Gilead Sciences, aims to understand the study drug GS-5319's dosing, safety, and tolerability. It focuses on adults living with advanced solid tumors who have a specific gene alteration in their tumor, which affects the production of the methylthioadenosine phosphorylase (MTAP) enzyme. The study is designed to enroll up to 178 participants and includes two parts: Part A for monotherapy dose escalation and Part B for monotherapy dose expansion. This research is crucial for determining how GS-5319 behaves in the body and if it can be a safe and effective treatment option for this patient population.
Where to Participate
The clinical trial for GS-5319 is currently recruiting participants across three study sites in the United States. These sites are located in different regions, making participation accessible to a broader patient population.
Eligibility for this study requires participants to be adults, specifically between the ages of 18 and 18 years. The study is open to all genders. It is important to note that healthy volunteers are not being recruited for this trial, nor are children eligible to participate.
Current recruiting locations include:
- Boston, Massachusetts
- San Antonio, Texas
- Fairfax, Virginia
Development Timeline
The journey of GS-5319 in clinical development began with initial investigations into its potential for conditions such as Irritable Bowel Syndrome with Constipation (IBS-C) and hyperphosphatemia. This early exploration laid the groundwork for understanding the drug's mechanisms.
Over time, the development pipeline for GS-5319 expanded, shifting its focus to oncology. The first clinical trial specifically targeting advanced solid tumors is anticipated to commence on August 17, 2025. This pivotal Phase 1 study, sponsored by Gilead Sciences, marks a significant milestone in the drug's progression.
To date, a single Phase 1 trial is recorded for GS-5319, with an enrollment target of 178 participants. This trial represents the current frontier of research for GS-5319, aiming to establish its safety and optimal dosing in a new therapeutic area.