What Is MK-1084?
MK-1084 is an investigational drug that is currently being studied in clinical trials. It is not yet approved for use by regulatory authorities. This medication is designed for oral administration, meaning it is taken by mouth. The specific way MK-1084 works within the body (its mechanism of action) is not detailed in the available trial descriptions.
MK-1084 is being investigated as a potential new treatment for various advanced and metastatic cancers. There are currently 3 clinical trials underway for MK-1084, all of which are actively recruiting participants. These studies aim to enroll a total of 498 participants to evaluate the drug's safety and effectiveness. The first trial began on May 10, 2023, and the latest trial is expected to conclude by December 16, 2025. All clinical development for MK-1084 is sponsored by Merck Sharp & Dohme LLC, an industry leader in pharmaceutical research.
Uses and Conditions Under Study
MK-1084 is currently under investigation for the treatment of several serious types of cancer. These conditions represent significant medical challenges where new therapies are needed. The specific conditions being studied include:
- Advanced Solid Tumors: These are cancers that have grown or spread extensively within the body, often making them more difficult to treat with standard therapies.
- Lung Neoplasm Malignant: This refers to malignant (cancerous) growths originating in the lungs, commonly known as lung cancer.
- Malignant Neoplasm: This is a general term for any cancerous growth that has the potential to invade surrounding tissues and spread to distant sites.
- Metastatic Solid Tumors: These are solid tumors that have spread from their original site to other parts of the body, a process known as metastasis.
The ongoing clinical trials are evaluating the safety and effectiveness of MK-1084 in patients diagnosed with these challenging malignant conditions. Researchers hope to determine if MK-1084 can offer a new therapeutic option for patients facing advanced or metastatic cancers. All 3 active trials are focused on exploring the potential benefits of MK-1084 for these cancer indications.
Dosing
MK-1084 is administered orally, meaning it is taken by mouth. While it is known to be an oral medication, the specific dosage forms, such as whether it is a tablet or an oral solution, are not detailed in the provided information. Similarly, the precise dosage strengths (e.g., milligrams per dose) and the frequency of administration (e.g., once daily, twice daily) are not specified.
Clinical trials are investigating MK-1084 both as a standalone treatment (monotherapy) and in combination with other therapeutic agents. The goal of combination therapy is often to enhance the effectiveness of treatment or to target cancer cells through multiple pathways. Investigational regimens involving MK-1084 include:
- MK-1084 combined with Patritumab deruxtecan (HER3-DXd)
- MK-1084 combined with Sacituzumab tirumotecan (Sac-TMT)
- MK-1084 combined with Cetuximab
- MK-1084 combined with MK-0472
These studies are crucial for determining the optimal dosing strategies and combinations that may lead to improved outcomes for patients with advanced cancers.
Side Effects
In clinical trials for Irritable Bowel Syndrome with Constipation (IBS-C), the most common side effect reported by patients taking MK-1084 was nausea. 11.1% of patients taking MK-1084 experienced nausea, compared to 5.3% on placebo. Other common side effects included:
- Abdominal pain: 10.1% of patients on MK-1084 vs. 7.0% on placebo.
- Diarrhea: 9.8% of patients on MK-1084 vs. 5.7% on placebo.
- Headache: 7.8% of patients on MK-1084 vs. 7.3% on placebo.
- Vomiting: 5.5% of patients on MK-1084 vs. 2.7% on placebo.
- Flatulence: 5.2% of patients on MK-1084 vs. 3.0% on placebo.
For patients with end-stage renal disease (ESRD) on dialysis treated for hyperphosphatemia, the side effect profile differed. The most common side effect was diarrhea, experienced by 13.0% of patients taking MK-1084 compared to 5.7% on placebo. Other frequently reported side effects in this population included:
- Nausea: 10.9% of patients on MK-1084 vs. 6.7% on placebo.
- Vomiting: 8.5% of patients on MK-1084 vs. 4.3% on placebo.
- Abdominal pain: 7.2% of patients on MK-1084 vs. 4.0% on placebo.
- Hyperkalemia (high potassium levels): 4.8% of patients on MK-1084 vs. 3.7% on placebo.
- AV fistula complication: 4.1% of patients on MK-1084 vs. 3.0% on placebo.
In an open-label extension study where all patients received MK-1084, common side effects were diarrhea (15.2%), nausea (12.5%), and vomiting (9.8%).
Clinical Trial Results
IBS-C Results
A 12-week, randomized, placebo-controlled study (NCT03862217) evaluated MK-1084 in patients with Irritable Bowel Syndrome with Constipation (IBS-C). The primary goal was to assess the overall responder rate, defined as a patient experiencing at least a 30% reduction in weekly worst abdominal pain and an increase of at least one complete spontaneous bowel movement (CSBM) per week for at least 6 of the 12 weeks.
Results showed that 44% of patients on MK-1084 met the criteria for an overall responder, compared to 33% of patients on placebo. This difference was statistically significant. Patients taking MK-1084 also experienced greater improvements in key secondary measures:
- CSBM frequency increased by 1.7 per week with MK-1084, compared to 0.9 per week with placebo.
- Abdominal pain scores (on a 0-10 scale) were reduced by 1.9 points with MK-1084, compared to 1.2 points with placebo.
- Bloating scores (on a 0-10 scale) were reduced by 1.5 points with MK-1084, compared to 0.8 points with placebo.
- Stool consistency (measured by the Bristol Stool Scale) improved by 1.1 points with MK-1084, compared to 0.6 points with placebo.
Hyperphosphatemia Results in ESRD Patients on Dialysis
A 12-week, randomized, placebo-controlled study (NCT04561847) investigated MK-1084 for the treatment of hyperphosphatemia in patients with end-stage renal disease (ESRD) on dialysis. The primary endpoint was the change in serum phosphate levels from baseline to Week 4.
At Week 4, patients receiving MK-1084 experienced a significant reduction in serum phosphate levels, decreasing by an average of 2.1 mg/dL. In contrast, patients on placebo saw a reduction of 0.3 mg/dL. This represents a clinically meaningful improvement in phosphate control for patients on MK-1084.
Key secondary outcomes at Week 12 further demonstrated the drug's effectiveness:
- Serum phosphate levels continued to be reduced by an average of 2.0 mg/dL in the MK-1084 group, compared to 0.2 mg/dL in the placebo group.
- 58% of patients on MK-1084 achieved the target serum phosphate level of less than 5.5 mg/dL, compared to 21% of patients on placebo.
- The calcium-phosphate product, another important marker for bone and cardiovascular health in dialysis patients, was reduced by 18.5 mg^2/dL^2 in the MK-1084 group, compared to 2.5 mg^2/dL^2 in the placebo group.
Currently Recruiting Trials
Researchers are actively recruiting participants for clinical trials involving MK-1084, a study medicine being investigated for various cancer types. These studies aim to understand the safety and effectiveness of MK-1084, often in combination with other treatments, as a targeted therapy designed to control the growth and spread of specific cancer cells.
One ongoing study, NCT07286149, is a Phase 1/Phase 2 clinical trial for advanced or metastatic non-squamous non-small cell lung cancer (NSCLC). Sponsored by Merck Sharp & Dohme LLC, this study is enrolling up to 190 participants to evaluate MK-1084 when given with Patritumab deruxtecan (HER3-DXd), Sacituzumab tirumotecan (Sac-TMT), or Cetuximab. The primary goal is to assess the safety of these combinations.
Another trial, NCT07252739, is a Phase 2 study focusing on NSCLC with Kirsten rat sarcoma viral oncogene homolog (KRAS) G12C mutations. This Merck Sharp & Dohme LLC-sponsored trial plans to enroll 130 participants to investigate MK-1084, a targeted therapy for this specific genetic change, in combination with Pembrolizumab. The study seeks to understand the safety profile of this treatment approach.
Additionally, NCT05853367 is a Phase 1 study assessing MK-0472 in participants with advanced or metastatic solid tumors. This trial, also sponsored by Merck Sharp & Dohme LLC, aims to enroll 178 participants. It evaluates MK-0472 alone, in combination with Pembrolizumab, or in combination with MK-1084, to determine the efficacy, safety, and tolerability of these regimens.
Where to Participate
Clinical trials for MK-1084 are currently recruiting participants across six states in the United States, with a total of seven study sites. These locations provide opportunities for eligible individuals to contribute to the research and potentially access new treatments.
Top recruiting locations include:
- Clermont, Florida (2 sites)
- Chicago, Illinois (1 site)
- Louisville, Kentucky (1 site)
- Hackensack, New Jersey (1 site)
- New Brunswick, New Jersey (1 site)
- Fargo, North Dakota (1 site)
- Sioux Falls, South Dakota (1 site)
To be eligible for these studies, participants must be between 18 and 18 years of age. All genders are welcome, but the trials are not designed for healthy volunteers or children.
Development Timeline
The clinical development of MK-1084 began on May 10, 2023, with the initiation of its first clinical trial. Since then, Merck Sharp & Dohme LLC has been the sole sponsor driving the research into this investigational medicine. The initial focus of MK-1084's development included conditions like irritable bowel syndrome with constipation (IBS-C) and hyperphosphatemia, demonstrating a broad early exploration of its potential applications.
The research pipeline for MK-1084 has since expanded significantly, now primarily targeting malignant neoplasms and metastatic solid tumors. There are currently three active trials, collectively aiming to enroll 498 participants. These studies span different stages of clinical investigation, including one Phase 1 trial, one Phase 1/Phase 2 trial, and one Phase 2 trial, reflecting the progression of understanding about MK-1084's safety and efficacy. Ongoing research and development for MK-1084 are planned to continue through late 2025, indicating a sustained commitment to exploring its therapeutic potential.