MK-1084 for Liver Disease

Recruiting at 2 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Merck Sharp & Dohme LLC

Must not be taking: HIV protease inhibitors

Disqualifiers: Gastrointestinal disease, Cancer, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

Duration: 1 day

58 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

The trial aims to understand how the body processes a new treatment called MK-1084 (experimental treatment) and to ensure its safety and tolerability, particularly for individuals with liver problems. Participants will include those with stable liver impairment (long-term liver issues with signs of cirrhosis) and healthy individuals. Those with a stable liver condition who can manage daily activities without severe issues may be suitable for the study. As a Phase 1 trial, this research focuses on understanding the treatment's effects in people, offering participants the opportunity to be among the first to receive it.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but if you are using HIV protease inhibitors or have received antiviral therapy for hepatitis B or C recently, you may not be eligible to participate.

Is there any evidence suggesting that MK-1084 is likely to be safe for humans?

Research has shown that MK-1084 is generally safe. In previous studies, only about 10% of patients experienced serious liver problems, indicating that most did not have severe liver issues. MK-1084 has also been combined with other treatments and remained safe for most individuals, suggesting that many can take it without major side effects. However, this trial is in the early stages, focusing on the drug's mechanism in the body and its initial safety in humans. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for liver disease focus on managing symptoms or slowing disease progression, often involving complex medication regimens or invasive procedures. MK-1084 is unique because it offers a new, potentially simpler approach with a single oral dose. Researchers are particularly excited about MK-1084 because it may work through a novel mechanism not yet utilized by existing treatments, potentially leading to more effective management of liver disease. This fresh approach could open up new possibilities for treating patients more efficiently and with fewer side effects.

What evidence suggests that MK-1084 might be an effective treatment for liver disease?

Research has shown that MK-1084 may help treat certain cancers, such as colorectal cancer and non-small cell lung cancer. In earlier studies, about 19% of patients experienced tumor shrinkage when using MK-1084 alone. This treatment targets a specific change (KRAS G12C) that can cause cancer cells to grow. Early results suggest it might be safe, with only about 10% of patients experiencing serious liver problems. While this information primarily comes from cancer studies, it suggests that MK-1084 might also help with liver issues. In this trial, all participants will receive a single oral dose of MK-1084 on Day 1 to evaluate its potential effects on liver disease. ^{1 2 5 6 7}

Who Is on the Research Team?

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Are You a Good Fit for This Trial?

This trial is for individuals with chronic, stable liver disease and features of cirrhosis, as well as healthy volunteers. Participants must have a BMI between 18.0 and 42.0 kg/m2. Those who are medically healthy without significant medical history can also join.

Inclusion Criteria

I have long-term liver disease with cirrhosis.

I am generally healthy with no major medical issues.

The main

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive a single oral dose of MK-1084 on Day 1

1 day

1 visit (in-person)

Pharmacokinetic Monitoring

Blood samples are collected to determine pharmacokinetic parameters of MK-1084

7 days

Multiple visits (in-person) for blood sampling

Follow-up

Participants are monitored for safety and adverse events

14 days

What Are the Treatments Tested in This Trial?

Interventions

• MK-1084

Trial Overview

The study focuses on MK-1084 and its behavior in the body over time, especially in those with liver impairment compared to healthy individuals. It aims to understand how different levels of liver health affect the drug's presence in the body.

How Is the Trial Designed?

Group I: MK-1084 Experimental Treatment 1 Intervention

All participants will receive a single oral dose of MK-1084 on Day 1.

Who Is Running the Clinical Trial?

Merck Sharp & Dohme LLC

Lead Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Citations

1.

merck.com

merck.com/news/merck-announces-mk-1084-an-investigational-kras-g12c-inhibitor-shows-antitumor-activity-in-phase-1-trial-of-patients-with-advanced-colorectal-cancer-and-non-small-cell-lung-cancer-whose-tumors-harbo/

Merck Announces MK-1084, an Investigational KRAS ...

For efficacy, the study evaluated overall response rate (ORR), with the following results for efficacy evaluable patients: MK-1084 Monotherapy.

2.

targetedonc.com

targetedonc.com/view/overview-of-the-mechanism-of-action-of-mk-1084

Overview of the Mechanism of Action of MK-1084

1:02 | [With] the combination, we did not see a high number of liver toxicity, it was like 10% of the patients on grade 3 or more than that.

3.

annalsofoncology.org

annalsofoncology.org/article/S0923-7534(24)02966-1/pdf

1392TiP Phase III study of pembrolizumab plus MK-1084 ...

Among patients who received first-line treatment for stage IV disease, median PFS was 5.15 mo with ICI alone or in combination with chemotherapy and 2.82 mo for ...

4.

merck.com

merck.com/news/merck-initiates-phase-3-clinical-trial-of-mk-1084-an-investigational-oral-kras-g12c-inhibitor-in-combination-with-keytruda-pembrolizumab-for-first-line-treatment-of-certain-patients-with-met/

Merck Initiates Phase 3 Clinical Trial of MK-1084, an ...

Merck has initiated a Phase 3, randomized, double-blind, multicenter clinical trial (NCT06345729) evaluating once daily MK-1084 in combination with KEYTRUDA.

5.

cancernetwork.com

cancernetwork.com/view/pembrolizumab-mk-1084-combo-is-the-focus-of-phase-3-trial-in-kras-g12c-metastatic-nsclc

Pembrolizumab/MK-1084 Combo Is the Focus of Phase 3 ...

Findings from the phase 1 trial highlighted an overall response rate (ORR) of 19% (n = 8/42) among patients who received MK-1084 monotherapy in ...

6.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05067283

NCT05067283 | A Study of MK-1084 in KRAS Mutant ...

This is a study evaluating the safety, pharmacokinetics, and efficacy of MK-1084 alone, and MK-1084 plus other combination therapies in participants with ...

7.

fiercebiotech.com

fiercebiotech.com/biotech/mercks-early-kras-data-suggests-combination-friendly-safety

Merck's early KRAS data suggest combination-friendly safety

Revealed at ESMO, MK-1084 alone posted an objective response rate (ORR) of 22% across all doses and tumor types during dose escalation after ...