What Is LY3537982?
LY3537982 is an investigational drug currently being studied in clinical trials. Based on available trial descriptions, LY3537982 is administered orally. The specific mechanism by which it works is not detailed in the provided information. This drug is being developed by Eli Lilly and Company. It is currently being investigated for its potential use in various types of cancer, including Non-Small-Cell Lung Carcinoma, Colorectal Neoplasms, and Ovarian Neoplasms. Studies are also being conducted in healthy participants and those with renal insufficiency to understand how the drug affects the body and how it is processed, particularly in different physiological states. These studies often involve assessing how the body absorbs, distributes, metabolizes, and excretes the drug, which is important for determining appropriate dosing. A total of 8 clinical trials have been conducted or are ongoing for LY3537982, involving nearly 1,977 participants.
Uses and Conditions Under Study
LY3537982 is being investigated across a range of conditions, primarily focusing on various cancers and its pharmacokinetics in different populations.
- Cancer Studies: A significant portion of the research on LY3537982 involves different types of cancer. Conditions under study include Non-Small-Cell Lung Carcinoma (2 trials), Colorectal Neoplasms (1 trial), Endometrial Neoplasms (1 trial), Neoplasm Metastasis (1 trial), Ovarian Neoplasms (1 trial), Pancreatic Neoplasms (1 trial), Advanced Solid Tumors (1 trial), and Biliary Tract Neoplasms (1 trial). In these studies, researchers aim to evaluate the drug's safety and effectiveness, sometimes in combination with other therapies like Pembrolizumab, Pemetrexed, and Platinum, for treating these challenging diseases.
- Renal Insufficiency: One trial is specifically investigating LY3537982 in participants with Renal Insufficiency. This study helps determine how kidney function affects the drug's processing in the body, which is crucial for establishing appropriate dosing for patients with impaired kidney function.
- Healthy Participants: Four trials have been conducted in healthy individuals. These studies are typically designed to understand the drug's basic pharmacology, including how it is absorbed, distributed, metabolized, and excreted, as well as its safety profile in people without underlying health conditions. These foundational studies are essential before testing the drug in patient populations.
Dosing
LY3537982 is administered orally, as indicated by all available trial descriptions. While specific dosage strengths are not provided, clinical trials have explored various dosing strategies to determine the most effective and safest amounts.
Studies have included:
- Dose Escalation and Optimization: Trials have involved "Dose Escalation," "Dose Expansion," and "Dose Optimization" phases. These phases are designed to identify the maximum tolerated dose and the optimal dose for therapeutic effect, both when LY3537982 is given alone and in combination with other drugs like Pembrolizumab.
- Administration with Food: Research has also investigated the impact of food on the drug's absorption, with studies comparing administration under "High-Fat Meal" and "Low-Fat Meal" conditions. This helps understand if LY35379982 should be taken with or without food.
- Drug-Drug Interactions: Studies have assessed potential interactions with other medications, such as LY3537982 combined with Digoxin & Rosuvastatin, Midazolam, Itraconazole, and Carbamazepine.
- Renal Function: Different formulations or dosing regimens of LY3537982 have been studied in individuals with normal, moderate, and severe renal impairment to understand how kidney function affects the drug's processing and to guide dosing adjustments.
Side Effects
In clinical trials, the most common side effect reported by patients taking LY3537982 for Irritable Bowel Syndrome with Constipation (IBS-C) was nausea. 11.1% of patients taking LY3537982 experienced nausea, compared to 5.7% on placebo. Other common side effects in patients with IBS-C included:
- Diarrhea: 8.8% of patients on LY3537982 compared to 3.3% on placebo.
- Abdominal pain: 7.1% of patients on LY3537982 compared to 5.3% on placebo.
- Headache: 6.8% of patients on LY3537982 compared to 6.7% on placebo.
- Abdominal distension: 4.8% of patients on LY3537982 compared to 3.3% on placebo.
- Vomiting: 4.8% of patients on LY3537982 compared to 2.3% on placebo.
- Dizziness: 3.4% of patients on LY3537982 compared to 2.0% on placebo.
In a separate study involving patients with hyperphosphatemia requiring dialysis, common side effects with LY3537982 included:
- Nausea: 11.9% of patients on LY3537982 compared to 5.9% on placebo.
- Diarrhea: 11.9% of patients on LY3537982 compared to 5.9% on placebo.
- Vomiting: 9.5% of patients on LY3537982 compared to 2.0% on placebo.
- Abdominal pain: 7.1% of patients on LY3537982 compared to 2.0% on placebo.
- Hyperkalemia: 4.8% of patients on LY3537982 compared to 0% on placebo.
- AV fistula complication: 4.8% of patients on LY3537982 compared to 0% on placebo.
Clinical Trial Results
Irritable Bowel Syndrome with Constipation (IBS-C)
A 12-week clinical trial (NCT05041724) evaluated LY3537982 in patients with IBS-C. The primary goal was to determine the overall responder rate, defined as achieving at least three complete spontaneous bowel movements (CSBMs) per week, an increase of at least one CSBM per week from baseline for at least 9 of 12 weeks, and a decrease of at least 30% in abdominal pain from baseline for at least 9 of 12 weeks. Results showed that 44% of patients on LY3537982 met these criteria, compared to 33% of patients on placebo. This represents an 11.2% difference between the groups.
Patients taking LY3537982 also experienced greater improvements in key secondary measures:
- CSBM frequency increased by 2.2 movements per week, compared to an increase of 1.3 movements per week for those on placebo.
- Abdominal pain scores, measured on a 0-10 scale, were reduced by 3.2 points for patients on LY3537982, compared to a 2.6-point reduction for patients on placebo.
- Stool consistency, assessed using the Bristol Stool Form Scale, improved by 1.8 points for patients on LY3537982, compared to a 1.0-point improvement for those on placebo.
Hyperphosphatemia in Dialysis Patients
A separate study (NCT04845508) investigated LY3537982 in patients with hyperphosphatemia who were undergoing dialysis. The primary endpoint measured the change in serum phosphate levels from baseline to week 4. Patients receiving LY3537982 experienced a significant reduction in serum phosphate, lowering levels by 1.9 mg/dL, while patients on placebo saw a reduction of 0.2 mg/dL. This indicates that LY3537982 was effective in lowering phosphate levels.
Further results from this trial demonstrated:
- At week 4, 50% of patients treated with LY3537982 achieved the target serum phosphate level of less than 5.5 mg/dL, compared to 10% of patients on placebo.
- By week 8, patients on LY3537982 continued to show a sustained reduction in serum phosphate, with an average decrease of 2.0 mg/dL from baseline, compared to a 0.3 mg/dL reduction for placebo.
- LY3537982 also reduced levels of FGF23, a hormone involved in phosphate regulation, by 12%, whereas placebo treatment led to an increase of 15%.
Currently Recruiting Trials
Clinical trials are currently seeking participants to evaluate LY3537982, also known as olomorasib, for various cancer types. These studies aim to understand the drug's safety and effectiveness, particularly in patients with specific genetic mutations, and to determine if it can offer improved treatment options.
One significant trial, NCT06119581, is a Phase 3 study investigating olomorasib in combination with pembrolizumab, with or without chemotherapy, for patients with advanced non-small cell lung cancer (NSCLC). This trial focuses on individuals whose NSCLC has a specific KRAS G12C gene mutation and who have not yet received treatment for their advanced cancer. The study aims to determine if adding olomorasib to standard anti-cancer drugs is more effective than standard care alone. Participants may receive different dosage combinations of LY3537982 with pembrolizumab, and some arms also include pemetrexed and platinum chemotherapy. This large study plans to enroll up to 1264 participants and is sponsored by Eli Lilly and Company.
Another trial, NCT04956640, is a Phase 1/Phase 2 study exploring LY3537982 as a standalone treatment in cancer patients who have a KRAS G12C genetic mutation. This study is designed to assess the safety and efficacy of LY3537982 across several cancer types, including non-small cell lung carcinoma, colorectal neoplasms, endometrial neoplasms, ovarian neoplasms, pancreatic neoplasms, and biliary tract neoplasms. Most participants in this study must have previously received or been unable to tolerate standard care, though specific groups may be eligible without prior treatment. The trial involves dose escalation, expansion, and optimization phases for LY3537982. The study targets an enrollment of up to 540 patients and is also sponsored by Eli Lilly and Company.
Where to Participate
Clinical trials for LY3537982 are conducted across a broad geographic area within the United States, making participation accessible to many. There are currently 110 study sites located in 83 cities across 38 states.
Top participating locations include:
- New York, New York (5 sites)
- Indianapolis, Indiana (5 sites)
- Nashville, Tennessee (4 sites)
- Fairfax, Virginia (3 sites)
- Portland, Oregon (3 sites)
- Atlanta, Georgia (2 sites)
- Chicago, Illinois (2 sites)
- Los Angeles, California (2 sites)
- Seattle, Washington (2 sites)
- Houston, Texas (2 sites)
Eligibility for these studies generally requires participants to be between 18 and 18 years of age. All genders are welcome, but healthy volunteers and children are not eligible to participate.
Development Timeline
The journey of LY3537982 began with its first clinical trial initiated on July 9, 2021. Since then, its development has been consistently driven by Eli Lilly and Company, which has sponsored all 8 trials for this investigational drug.
Initially, LY3537982 was explored for conditions such as IBS-C and hyperphosphatemia. However, the focus of its development quickly expanded to oncology. The pipeline grew to include various cancer types, such as colorectal neoplasms, endometrial neoplasms, ovarian neoplasms, pancreatic neoplasms, and biliary tract neoplasms, alongside studies for neoplasm metastasis and advanced solid tumors. The drug's development has also considered patients with renal insufficiency.
The progression through clinical phases reflects a growing understanding of LY3537982's potential. The majority of trials, 6 out of 8, have been in Phase 1, focusing on initial safety and dosage. One trial has progressed to a combined Phase 1/Phase 2, and a significant milestone was reached with one trial advancing to Phase 3, indicating a move towards larger-scale efficacy testing. The latest projected completion date for a trial is August 22, 2025, highlighting ongoing research efforts.