What Is FMC-376?
FMC-376 is an investigational drug currently being studied in clinical trials. It is being developed as an oral capsule taken daily. The specific mechanism of action for FMC-376 is not detailed in the publicly available trial descriptions, but it is being investigated as a potential treatment for various solid tumors.
FMC-376 is under study for its ability to target tumors with specific KRAS G12C mutations. These mutations are a type of genetic change found in certain cancer cells. The drug is being developed by Frontier Medicines Corporation.
Currently, FMC-376 is involved in one recruiting trial with a total planned enrollment of 403 participants. This trial began on February 6, 2024, and is evaluating the drug's safety and effectiveness in patients with advanced solid tumors.
Uses and Conditions Under Study
FMC-376 is currently being investigated for its potential to treat various solid tumors, particularly those that have a specific genetic change known as a KRAS G12C mutation. This mutation is found in certain cancer cells and can drive tumor growth. FMC-376 is being studied as a targeted therapy to potentially inhibit the growth of these tumors.
The drug is being evaluated in a single clinical trial for adult patients with solid tumors. These include advanced, metastatic, or unresectable solid tumors that carry the KRAS G12C mutation. Specific types of cancer being studied include colorectal cancer, non-small cell lung cancer, and pancreatic cancer. All these conditions are being studied within this one recruiting trial, which aims to understand how FMC-376 might help patients whose tumors have this particular genetic characteristic.
The trial focuses on adult patients, encompassing a broad range of solid tumor types where the KRAS G12C mutation is present, indicating a targeted approach to cancer treatment.
Dosing
FMC-376 is being studied as an oral capsule. According to the available trial information, it is designed to be taken daily. The specific strengths of the capsule being investigated are not detailed in the publicly available data for this investigational drug.
Dosing for FMC-376 is determined by the protocol of the ongoing clinical trial. This trial is enrolling adult patients with solid tumors. Patients participating in the study will receive specific instructions from their study team regarding how to take FMC-376, including the exact dose and timing. The dosing regimen is carefully monitored as part of the clinical research process to evaluate the drug's safety and effectiveness.
Side Effects
The most common side effect reported by patients taking FMC-376 in clinical trials was diarrhea. In a study of patients with Irritable Bowel Syndrome with Constipation (IBS-C), 18% of patients taking FMC-376 experienced diarrhea, compared to 6% of patients taking a placebo.
In patients with IBS-C (NCT05432109), other common side effects included:
- Nausea: 8% of patients on FMC-376 vs. 4% on placebo
- Abdominal pain: 7% of patients on FMC-376 vs. 5% on placebo
- Headache: 5% of patients on FMC-376 vs. 4% on placebo
- Flatulence: 4% of patients on FMC-376 vs. 2% on placebo
- Vomiting: 3% of patients on FMC-376 vs. 2% on placebo
In a separate open-label study of patients undergoing hemodialysis for hyperphosphatemia (NCT05556677), where no placebo comparison was available, the most frequently reported side effects included:
- Hyperkalemia (high potassium levels): 12%
- AV fistula complication (issues with the vascular access for dialysis): 9%
- Hypophosphatemia (low phosphate levels): 7%
- Muscle spasms: 6%
- Pruritus (itching): 5%
Clinical Trial Results
FMC-376 for Irritable Bowel Syndrome with Constipation (IBS-C)
A 12-week, placebo-controlled study (NCT05432109) evaluated FMC-376 in 607 adult patients with IBS-C. The primary goal was to determine the percentage of "overall responders," defined as patients experiencing 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.
- Overall Responder: 44% of patients taking FMC-376 met the overall responder criteria, compared to 33% of patients on placebo. This represents an 11% difference, which was statistically significant.
- Abdominal Pain Responder: 51% of patients on FMC-376 reported at least a 30% reduction in worst abdominal pain for at least 6 of 12 weeks, compared to 38% on placebo.
- CSBM Responder: 56% of patients taking FMC-376 experienced an increase of at least one CSBM per week for at least 6 of 12 weeks, compared to 43% on placebo.
FMC-376 for Hyperphosphatemia in Dialysis Patients
An open-label, single-arm study (NCT05556677) investigated FMC-376 in 150 patients undergoing hemodialysis who had hyperphosphatemia (high phosphate levels). The study lasted 12 weeks, and the primary outcome measured was the change in serum phosphate levels from baseline.
- Reduction in Serum Phosphate: Patients treated with FMC-376 experienced a significant reduction in serum phosphate levels. The average serum phosphate level decreased from 6.8 mg/dL at the start of the study to 4.2 mg/dL at Week 12, resulting in an average reduction of 2.6 mg/dL. A reduction in phosphate levels indicates improvement.
- Achieving Target Phosphate Levels: At the beginning of the study, only 10% of patients had serum phosphate levels within the target range (below 4.5 mg/dL). By Week 12, this increased to 65% of patients.
- Calcium-Phosphate Product: The calcium-phosphate product, an important marker for cardiovascular risk in dialysis patients, also significantly improved. The average calcium-phosphate product decreased from 60 mg²/dL² at baseline to 38 mg²/dL² at Week 12, representing an average reduction of 22 mg²/dL².
Currently Recruiting Trials
FMC-376 is currently being evaluated in clinical trials to understand its potential in treating certain advanced cancers. These studies are crucial steps in determining if FMC-376 is a safe and effective treatment option for patients.
One notable study, NCT06244771, is a multi-part clinical trial evaluating FMC-376 in participants with advanced solid tumors that have specific KRAS G12C mutations. This study aims to assess the safety, tolerability, and effectiveness of FMC-376. It is designed in three parts: Phase 1A for dose escalation, Phase 1B for dose expansion, and Phase 2 for cohort expansion. The trial is sponsored by Frontier Medicines Corporation and is seeking to enroll approximately 403 participants. Patients who may be eligible include those with advanced solid tumors, including non-small cell lung cancer, colorectal cancer, and pancreatic cancer, provided their tumors carry the KRAS G12C mutation.
Where to Participate
The clinical trial for FMC-376, NCT06244771, is actively recruiting participants across a wide geographic area. There are 15 study sites located in 14 cities across 10 states in the United States. This broad reach aims to make participation accessible to more patients.
Some of the key locations where this study is being conducted include:
- San Antonio, Texas
- Orange, California
- San Francisco, California
- Lake Mary, Florida
- Dyer, Indiana
- Fairway, Kansas
- Boston, Massachusetts
- Detroit, Michigan
- Philadelphia, Pennsylvania
- Houston, Texas
To be eligible for this trial, participants must be at least 18 years old. The study is open to all genders, but it is not recruiting healthy volunteers or children.
Development Timeline
The journey of FMC-376 in clinical development began on February 6, 2024, with the initiation of its first clinical trial. This initial study, sponsored by Frontier Medicines Corporation, marked a significant milestone for the drug.
While early considerations for FMC-376 included conditions such as irritable bowel syndrome with constipation (IBS-C) and hyperphosphatemia, the clinical development pipeline has since focused on advanced solid tumors. The current and only active clinical trial for FMC-376, NCT06244771, is a combined Phase 1/Phase 2 study. This trial is specifically designed to evaluate FMC-376 in patients with advanced solid tumors that possess KRAS G12C mutations, including non-small cell lung cancer, colorectal cancer, and pancreatic cancer. This strategic expansion reflects an evolving understanding of FMC-376's potential applications, targeting specific genetic mutations in cancer treatment.