MK-2225 Safety Study

Recruiting at 1 trial location

Overseen By Toll Free Number

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Merck Sharp & Dohme LLC

Disqualifiers: Endocrine, Cardiovascular, Neurological, others

Compensation: Varies

Number of Visits: Unknown

Duration: 8 weeks

32 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of the study is to learn about the safety of MK-2225, including how well people tolerate it. Researchers also want to learn what happens to different doses of MK-2225 in a person's body over time.

Do I need to stop my current medications for the MK-2225 trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug MK-2225?

The research on MK-2206, a similar drug that inhibits AKT, showed that some patients with uterine serous carcinoma experienced progression-free survival for at least 6 months, indicating potential effectiveness in certain cancer types. However, the overall activity was limited, suggesting that further studies are needed to better understand its benefits. ^{1 2 3 4 5}

What safety data exists for MK-2225 or similar treatments?

The safety of small molecule kinase inhibitors, like MK-2225, has been studied in various trials. These drugs can increase the risk of serious and fatal adverse events, so efforts are needed to manage these risks. Nonclinical evaluations help predict some adverse effects, but improvements in safety databases and modeling are needed for better predictions. ^{6 7 8 9 10}

Research Team

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Eligibility Criteria

This clinical trial is for healthy individuals who are interested in contributing to research on a new medication, MK-2225. Specific eligibility criteria were not provided, so it's important to contact the study organizers for detailed requirements.

Inclusion Criteria

Is in good health before randomization

Body Mass Index (BMI) ≤32 kg/m^2, inclusive

Exclusion Criteria

History of clinically significant immunological abnormalities

I have had serious lung or breathing problems.

History of clinically significant hematological abnormalities

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive MK-2225 or placebo subcutaneously every 2 weeks over the course of 8 weeks

8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

8-12 weeks

Treatment Details

Interventions

• MK-2225

Trial Overview The study is testing the safety and tolerability of different doses of a new drug called MK-2225 compared to a placebo (a substance with no active drug). It also examines how the body processes the drug over time.

Participant Groups

Group I: MK-2225 Panel D Experimental Treatment 1 Intervention

Participants receive MK-2225 Dose 4 SQ Q2W over the course of 8 weeks based on the safety and tolerability of the previous starting dose.

Group II: MK-2225 Panel C Experimental Treatment 1 Intervention

Participants receive MK-2225 Dose 3 SQ Q2W over the course of 8 weeks based on the safety and tolerability of the previous starting dose.

Group III: MK-2225 Panel B Experimental Treatment 1 Intervention

Participants receive MK-2225 Dose 2 SQ Q2W over the course of 8 weeks based on the safety and tolerability of the previous starting dose.

Group IV: MK-2225 Panel A Experimental Treatment 1 Intervention

Participants receive MK-2225 Dose 1 subcutaneously (SQ) once every 2 weeks (Q2W) over the course of 8 weeks.

Group V: Placebo Placebo Group 1 Intervention

Participants receive placebo SQ Q2W over the MK-2225-matched time period.

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

Findings from Research

In a study involving 20 Japanese patients with advanced colorectal cancer, the combination of MK-0646 with cetuximab and irinotecan was found to be well tolerated, with only one patient experiencing a dose-limiting toxicity (grade 3 hyperglycemia).

The combination therapy increased the exposure of MK-0646 by 25% without affecting the pharmacokinetics of cetuximab and irinotecan, although it did reduce the levels of SN-38, the active metabolite of irinotecan, indicating minimal drug interactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 pharmacokinetic study of MK-0646 (dalotuzumab), an anti-insulin-like growth factor-1 receptor monoclonal antibody, in combination with cetuximab and irinotecan in Japanese patients with advanced colorectal cancer. Doi, T., Muro, K., Yoshino, T., et al.[2021]

The maximum tolerated dose (MTD) of MK-2206 was determined to be 45 mg every other day or 200 mg every three weeks, with common side effects including fatigue, nausea, and skin rash.

In this phase 1 study involving 72 patients with advanced solid tumors, MK-2206 showed promising antitumor activity when combined with chemotherapy and targeted therapies, with some patients experiencing complete or partial responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 trial of the oral AKT inhibitor MK-2206 plus carboplatin/paclitaxel, docetaxel, or erlotinib in patients with advanced solid tumors. Molife, LR., Yan, L., Vitfell-Rasmussen, J., et al.[2021]

In a study involving 71 patients with advanced cancers, MK-2206, a pan-AKT inhibitor, was found to safely block the AKT signaling pathway, with a maximum tolerated dose of 200 mg when administered weekly (QW).

Both the weekly and alternate day (QOD) dosing schedules were well-tolerated, showing similar safety profiles, and the study successfully implemented complex MRI imaging techniques to monitor treatment effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interrogating two schedules of the AKT inhibitor MK-2206 in patients with advanced solid tumors incorporating novel pharmacodynamic and functional imaging biomarkers. Yap, TA., Yan, L., Patnaik, A., et al.[2022]

The maximum-tolerated dose (MTD) of MK-0457, a novel pan-Aurora kinase inhibitor, was determined to be 64 mg/m²/h, with dose-limiting toxicities including severe neutropenia and herpes zoster observed at higher doses.

MK-0457 was generally well tolerated, with nearly half of the 27 patients experiencing stable disease, suggesting potential efficacy, particularly in combination with other cancer treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I dose escalation study of MK-0457, a novel Aurora kinase inhibitor, in adult patients with advanced solid tumors. Traynor, AM., Hewitt, M., Liu, G., et al.[2022]

In a phase II study involving 14 patients with advanced uterine serous carcinoma (USC), the AKT inhibitor MK-2206 showed limited efficacy, with a clinical benefit rate of 14.3% and a median progression-free survival of only 2 months.

Despite the overall limited activity, one patient achieved a partial response and remained progression-free for 6 months, suggesting that some patients may benefit from this treatment, warranting further research to identify responsive patient characteristics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of MK-2206, an AKT inhibitor, in uterine serous carcinoma. Stover, EH., Xiong, N., Myers, AP., et al.[2022]

The safety of marketed drugs is a significant concern, as some commonly prescribed medications can lead to serious or life-threatening side effects in patients.

The ChEMBL resource will provide a curated drug safety data set, including toxicity classifications and black box warnings, which will be freely available and regularly updated to aid in drug safety research and discovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug Safety Data Curation and Modeling in ChEMBL: Boxed Warnings and Withdrawn Drugs. Hunter, FMI., Bento, AP., Bosc, N., et al.[2023]

A meta-analysis of 53 Phase II/III/IV trials involving nearly 20,000 patients revealed that molecular target anticancer drugs significantly increase the risk of serious adverse events (SAEs) by 57% and fatal adverse events (FAEs) by 51% compared to placebo.

The overall incidence rates for SAEs and FAEs were found to be 26.9% and 2.3%, respectively, highlighting the need for careful monitoring and preventive measures for patients receiving these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk of serious adverse event and fatal adverse event with molecular target anticancer drugs in cancer patients: A meta-analysis. Wang, Z., Yang, X., Wang, J., et al.[2020]

A systematic review of 26 studies on multi-targeted kinase inhibitors for advanced cancer revealed that common side effects include diarrhea, fatigue, nausea, and hypertension, affecting more than 10% of patients.

While adverse events are frequent with multi-kinase inhibitors, serious side effects are less common compared to traditional cytotoxic cancer therapies, indicating a potentially safer profile for these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of multi-targeted kinase inhibitors as monotherapy treatment of cancer: a systematic review of the literature. Crean, S., Boyd, DM., Sercus, B., et al.[2019]

Incorporating nonclinical pharmacologic and toxicologic assessments into the development of small-molecule oncology drugs can enhance the safety and efficacy profiles, particularly for kinase inhibitors, which often have unpredictable adverse effects.

Improving databases on adverse effects and better understanding drug target biology can lead to more accurate predictions of toxicity, allowing for the design of safer and more selective kinase inhibitors in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nonclinical Evaluations of Small-Molecule Oncology Drugs: Integration into Clinical Dose Optimization and Toxicity Management. Dambach, DM., Simpson, NE., Jones, TW., et al.[2018]

A machine-learning model was developed using data from 4638 patients across 16 FDA-approved small molecule kinase inhibitors (SMKIs) to analyze the relationship between kinase targets and adverse events (AEs), providing a new tool for predicting safety risks in cancer treatments.

The model not only helps identify potential kinase-inhibitor adverse event pairs but also serves as a precision medicine tool to enhance patient safety by forecasting clinical safety signals and aiding in the development of safer SMKI therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Decoding kinase-adverse event associations for small molecule kinase inhibitors. Gong, X., Hu, M., Liu, J., et al.[2022]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Phase 1 pharmacokinetic study of MK-0646 (dalotuzumab), an anti-insulin-like growth factor-1 receptor monoclonal antibody, in combination with cetuximab and irinotecan in Japanese patients with advanced colorectal cancer. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Phase 1 trial of the oral AKT inhibitor MK-2206 plus carboplatin/paclitaxel, docetaxel, or erlotinib in patients with advanced solid tumors. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Interrogating two schedules of the AKT inhibitor MK-2206 in patients with advanced solid tumors incorporating novel pharmacodynamic and functional imaging biomarkers. [2022]

4. Germany pubmed.ncbi.nlm.nih.gov

Phase I dose escalation study of MK-0457, a novel Aurora kinase inhibitor, in adult patients with advanced solid tumors. [2022]

5. Netherlands pubmed.ncbi.nlm.nih.gov

A phase II study of MK-2206, an AKT inhibitor, in uterine serous carcinoma. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Drug Safety Data Curation and Modeling in ChEMBL: Boxed Warnings and Withdrawn Drugs. [2023]

7. India pubmed.ncbi.nlm.nih.gov

Risk of serious adverse event and fatal adverse event with molecular target anticancer drugs in cancer patients: A meta-analysis. [2020]

8. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Safety of multi-targeted kinase inhibitors as monotherapy treatment of cancer: a systematic review of the literature. [2019]

9. United States pubmed.ncbi.nlm.nih.gov

Nonclinical Evaluations of Small-Molecule Oncology Drugs: Integration into Clinical Dose Optimization and Toxicity Management. [2018]

10. England pubmed.ncbi.nlm.nih.gov

Decoding kinase-adverse event associations for small molecule kinase inhibitors. [2022]