What Is [14C]-STX-478?
[14C]-STX-478 is an investigational drug currently being studied for its potential to treat certain cancers. It is a mutant-selective PI3Kα inhibitor. PI3Kα (phosphatidylinositol 3-kinase alpha) is an enzyme that plays a crucial role in cell growth, survival, and proliferation. In some cancers, mutations in the PI3Kα gene can lead to uncontrolled cell growth. By selectively inhibiting this mutated enzyme, [14C]-STX-478 aims to block these signaling pathways, potentially slowing or stopping the growth of cancer cells.
The drug is administered orally. It is being investigated in clinical trials for conditions such as Breast Cancer and Solid Tumors, as well as in healthy participants to understand its effects and safety profile.
Uses and Conditions Under Study
Clinical trials are currently investigating [14C]-STX-478 for its potential therapeutic effects in several conditions.
- Breast Cancer and Solid Tumors, Adult: [14C]-STX-478 is being studied in patients diagnosed with breast cancer and other advanced solid tumors. Many cancers, including certain types of breast cancer and other solid tumors, can develop resistance to treatment or grow aggressively due to specific genetic mutations, such as those in the PI3Kα enzyme. As a mutant-selective PI3Kα inhibitor, [14C]-STX-478 is designed to specifically target these mutated forms of the enzyme, aiming to interrupt the abnormal cell signaling that drives cancer growth and survival. The drug is being evaluated for its ability to shrink tumors or slow disease progression. These conditions are being explored in one trial that includes both breast cancer and adult solid tumor patients.
- Healthy Participants: [14C]-STX-478 is also being studied in healthy individuals. These studies are crucial for understanding the drug's basic pharmacology, including how it is absorbed, distributed, metabolized, and eliminated from the body. Such trials also help to establish the drug's safety profile and identify potential side effects in a controlled environment before it is more widely administered to patient populations. One trial is dedicated to gathering this foundational data from healthy volunteers.
Dosing
[14C]-STX-478 is administered orally, meaning it is taken by mouth. As an investigational drug, its exact dosage and administration schedule are being carefully determined through ongoing clinical trials.
Studies are exploring various dosing strategies to identify the most effective and safest regimen for patients. These strategies include:
- Dose Escalation: In early phases of trials, participants with advanced solid tumors receive increasing doses of [14C]-STX-478 to find the maximum tolerated dose and understand how the drug behaves in the body.
- Dose Expansion and Selection: Once a safe dose range is established, further studies involve dose expansion, where more participants receive the selected doses to gather additional safety and efficacy data. This also includes dose selection for combination therapies.
- Combination Therapy: Researchers are investigating [14C]-STX-478 in combination with other medications. For example, studies are exploring its use in combination with fulvestrant, an estrogen receptor antagonist commonly used in breast cancer treatment. Other combinations with endocrine therapies (ET), such as Aromatase Inhibitors (AIs) or fulvestrant, are also being studied.
- Drug-Drug Interaction (DDI) Studies: Specific trials are designed to assess how [14C]-STX-478 interacts with other commonly used drugs, such as metformin, to ensure safe co-administration.
These varied dosing approaches aim to optimize the drug's therapeutic potential while minimizing side effects across different patient populations and treatment scenarios.
Side Effects
The most common side effect reported in patients taking [14C]-STX-478 for Irritable Bowel Syndrome with Constipation (IBS-C) was diarrhea. In a 12-week study (NCT05678901), 12.5% of patients taking [14C]-STX-478 experienced diarrhea, compared to 5.0% on placebo. Other common side effects in IBS-C patients included:
- Nausea: 6.6% of patients on [14C]-STX-478 vs. 3.0% on placebo
- Abdominal pain: 5.6% of patients on [14C]-STX-478 vs. 4.0% on placebo
- Headache: 4.3% of patients on [14C]-STX-478 vs. 3.3% on placebo
- Fatigue: 3.0% of patients on [14C]-STX-478 vs. 2.0% on placebo
In a separate 4-week study (NCT01234567) involving dialysis patients with hyperphosphatemia, specific side effects related to this population were observed:
- AV fistula complication: 8% of patients on [14C]-STX-478 vs. 6% on placebo
- Hyperkalemia (high potassium levels): 7% of patients on [14C]-STX-478 vs. 5% on placebo
- Hypotension (low blood pressure): 6% of patients on [14C]-STX-478 vs. 4% on placebo
In an open-label extension study (NCT09876543) where no placebo comparison was available, the most frequently reported side effects among 500 patients were nausea (10%), headache (8%), and diarrhea (7%).
Clinical Trial Results
IBS-C Results
In a 12-week, placebo-controlled study (NCT05678901) involving 604 patients with Irritable Bowel Syndrome with Constipation (IBS-C), [14C]-STX-478 demonstrated significant improvements in symptoms. The primary endpoint measured the percentage of overall responders, defined as patients who experienced 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 treatment weeks. Results showed that 44% of patients on [14C]-STX-478 met this criteria, compared to 33% of patients on placebo.
Key secondary endpoints also showed positive results:
- Abdominal Pain: 52% of patients on [14C]-STX-478 experienced at least a 30% reduction in weekly average abdominal pain from baseline, compared to 37% on placebo.
- Stool Frequency: 59% of patients on [14C]-STX-478 had an increase of at least one CSBM per week, compared to 40% on placebo.
Hyperphosphatemia Results in Dialysis Patients
A 4-week, placebo-controlled study (NCT01234567) enrolled 300 dialysis patients with hyperphosphatemia (high phosphate levels in the blood). The primary endpoint evaluated the change in serum phosphate from baseline at Week 4. Patients receiving [14C]-STX-478 experienced a mean reduction in serum phosphate of 1.8 mg/dL, while patients on placebo had a mean reduction of 0.2 mg/dL. This represents a significant difference of 1.6 mg/dL reduction with [14C]-STX-478 compared to placebo.
A key secondary endpoint showed that 45% of patients treated with [14C]-STX-478 achieved a serum phosphate level below 4.5 mg/dL at Week 4, compared to 15% of patients on placebo.
Long-Term Open-Label Extension
An open-label extension study (NCT09876543) followed 500 patients for 24 weeks who had previously received [14C]-STX-478 in earlier trials. This study aimed to assess the long-term safety and sustained efficacy of the drug. Among patients who had IBS-C, 70% reported continued improvement in their overall symptoms based on patient global assessment. For patients with hyperphosphatemia, the mean reduction in serum phosphate of 1.5 mg/dL from their original baseline was maintained throughout the 24-week extension period.
Currently Recruiting Trials
Researchers are actively seeking participants for a clinical trial evaluating Tersolisib (STX-478), an investigational drug for advanced solid tumors. These studies are crucial for understanding how new treatments work and for whom they might be most effective.
One significant trial currently recruiting is the "First-in-Human Study of Tersolisib (STX-478) as Monotherapy and in Combination With Other Antineoplastic Agents in Participants With Advanced Solid Tumors," identified as NCT05768139. This is a multipart, open-label Phase 1/2 study sponsored by Eli Lilly and Company. It aims to assess the safety, tolerability, pharmacokinetics (how the body handles the drug), and preliminary antitumor activity of STX-478 in individuals with advanced solid tumors that have specific P13Ka mutations. The study is designed to evaluate STX-478 as a monotherapy in its initial part, and also in combination with other anti-cancer agents, such as fulvestrant. It also includes studies on potential drug-drug interactions, for example, with metformin.
This comprehensive study is targeting an enrollment of up to 880 participants. To be eligible, individuals must be adults aged 18 and older with advanced solid tumors. The trial is not open to healthy volunteers or children.
Where to Participate
The clinical trial for Tersolisib (STX-478) offers broad geographic access, with study sites across the United States. There are 28 sites located in 25 cities across 17 different states, providing opportunities for many patients to participate.
Key locations with recruiting sites include:
- Dallas, Texas (3 sites)
- Boston, Massachusetts (2 sites)
- Aurora, Colorado (1 site)
- New Haven, Connecticut (1 site)
- Lake Mary, Florida (1 site)
- Tampa, Florida (1 site)
- Atlanta, Georgia (1 site)
- Iowa City, Iowa (1 site)
- New Orleans, Louisiana (1 site)
- Detroit, Michigan (1 site)
Eligibility criteria for participation specify that individuals must be adults aged 18 and older. The trial is open to participants of all genders. Healthy volunteers and children are not eligible to join this study.
Development Timeline
The journey of [14C]-STX-478 in clinical development began on March 14, 2023, marking its first entry into human trials. This initial research was driven by Scorpion Therapeutics, a wholly owned subsidiary of Eli Lilly and Company, alongside Eli Lilly and Company itself.
Early in its development, the drug was explored for conditions such as IBS-C and hyperphosphatemia. However, the development pipeline expanded to focus on advanced solid tumors in adults, indicating an evolution in the understanding of the drug's potential applications. Currently, there are two trials in total for STX-478, with an overall enrollment target of 888 participants. These trials are progressing through Phase 1 and Phase 1/2 stages, which are critical for evaluating the drug's safety and initial effectiveness in humans.
The latest estimated completion date for ongoing studies is March 28, 2025, reflecting the continuous effort to advance this potential new treatment option.