MK-1484 + Pembrolizumab for Cancer

Not currently recruiting at 8 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Merck Sharp & Dohme LLC

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: CNS metastases, Active infection, Autoimmune, others

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

Compensation: Varies

Number of Visits: 3

Duration: Up to 24 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial evaluates whether a new drug, MK-1484 (an experimental treatment), alone or with pembrolizumab (also known as KEYTRUDA), is safe for people with advanced or metastatic solid tumors. Researchers aim to determine the best dose for future studies. Individuals with solid tumors that have not responded well to other treatments may be suitable candidates for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you must not have had chemotherapy, radiation, or biological cancer therapy within 4 weeks before starting the trial, and you should not be on chronic systemic steroid therapy exceeding 10 mg daily of prednisone equivalent within 7 days before the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that MK-1484 is a new treatment under testing to assess its safety. As an early-stage study, the main goal is to determine its tolerability. Although information is limited, early tests focus heavily on monitoring side effects.

Pembrolizumab is already used to treat some cancers and has undergone extensive study, generally proving safe when used alone. However, combining it with MK-1484 is new, making it crucial to observe their interaction in this trial.

Overall, the safety of MK-1484 and its combination with pembrolizumab remains under investigation. This trial will help identify safe doses for people with advanced cancers. Researchers will closely monitor participants for side effects to better understand the safety of these treatments. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of MK-1484 and pembrolizumab for cancer treatment because it represents a novel approach in immunotherapy. Unlike standard treatments that often focus on chemotherapy or targeted therapy, MK-1484 works by enhancing the immune system's ability to target and destroy cancer cells. This is achieved through a mechanism that potentially amplifies the effects of pembrolizumab, a well-known PD-1 inhibitor, making the combination more effective than using pembrolizumab alone. The prospect of using MK-1484 to increase the efficacy of pembrolizumab offers hope for improved outcomes in cancer treatment.

What evidence suggests that this trial's treatments could be effective for advanced or metastatic solid tumors?

Research shows that pembrolizumab, a key part of this trial, yields promising results for treating advanced cancers. Studies have demonstrated that pembrolizumab significantly improves survival rates compared to standard chemotherapy. For example, the five-year survival rate for patients using pembrolizumab was nearly double that of those using only chemotherapy. In this trial, some participants will receive MK-1484 alone, an experimental treatment that helps the immune system fight cancer. Although detailed human data remains limited, early signs suggest MK-1484 could enhance treatment effectiveness when combined with pembrolizumab. The combination of MK-1484 and pembrolizumab aims to strengthen the body's defense against cancer more effectively than using either treatment alone. ^{1 4 6 7 8}

Who Is on the Research Team?

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Are You a Good Fit for This Trial?

Adults with advanced or metastatic solid tumors who have tried all other treatments or can't tolerate them are eligible. They must have measurable disease, normal heart function, and adequate organ function. Participants need to provide a tumor sample for analysis and agree to use contraception. Excluded are those with certain lung conditions, recent transplants, active infections including HIV/HBV/HCV, uncontrolled diseases or conditions that could affect the trial's outcome.

Inclusion Criteria

Has measurable disease by Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 as assessed by the local site investigator/radiology.

My organs are functioning well.

I have given a tissue sample for cancer marker tests.

Exclusion Criteria

I have previously received IL-2 based therapy.

Participants with known human immunodeficiency virus (HIV) and/or hepatitis B or C infections, or known to be positive for hepatitis B surface antigen (HBsAg)/hepatitis B virus (HBV) DNA or hepatitis C Antibody or ribonucleic acid (RNA).

I have not had a live vaccine in the last 30 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive MK-1484 as monotherapy or in combination with pembrolizumab every 3 weeks for up to 35 cycles

Up to 24 months

Every 3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

What Are the Treatments Tested in This Trial?

Interventions

• MK-1484
• Pembrolizumab

Trial Overview The study is testing MK-1484 alone and combined with Pembrolizumab in patients with advanced solid tumors. It aims to find out how safe these treatments are and determine the best dose for Phase 2 trials.

How Is the Trial Designed?

Group I: MK-1484 + Pembrolizumab Experimental Treatment 2 Interventions

Participants will receive MK-1484 Q3W at escalating dose levels from 10-60 mg plus pembrolizumab 200 mg once every 21-day cycle for up to a total of 35 cycles (up to approximately 24 months).

Group II: MK-1484 Experimental Treatment 1 Intervention

Participants will receive MK-1484 every 3 weeks (Q3W) or 21-day cycle at escalating dose levels from 0.2-60 mg for up to a total of 35 cycles (up to approximately 24 months).

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

Published Research Related to This Trial

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating unresectable or metastatic melanoma based on two clinical trials involving 1,374 patients, showing significant improvements in overall survival compared to ipilimumab, with hazard ratios indicating a reduced risk of death.

Patients receiving pembrolizumab also experienced significant improvements in progression-free survival, although some immune-mediated adverse reactions like hypothyroidism and pneumonitis were noted, highlighting the importance of monitoring for side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. Barone, A., Hazarika, M., Theoret, MR., et al.[2022]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating advanced melanoma, showing an overall response rate of 24% in a trial of 89 patients, with 86% of responses lasting at least 6 months.

While there are potential immune-mediated side effects, the benefits of prolonged tumor response durations were deemed to outweigh these risks, marking an improvement over existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. Chuk, MK., Chang, JT., Theoret, MR., et al.[2021]

Nivolumab and pembrolizumab are FDA-approved monoclonal antibodies that target PD-1, helping to enhance T cell activity against cancer by blocking the PD-1/PD-L1 interaction, which allows cancer cells to escape immune detection.

Both drugs have shown efficacy across multiple cancer types, including melanoma and non-small cell lung cancer, and are considered interchangeable options for treating these conditions, which may help manage the rising costs of cancer therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab and pembrolizumab: Monoclonal antibodies against programmed cell death-1 (PD-1) that are interchangeable. Prasad, V., Kaestner, V.[2022]

Pembrolizumab, a PD-1 inhibitor, has demonstrated clinical effectiveness in treating various solid tumors, particularly in patients with PD-L1-positive non-small-cell lung cancer and unresectable/metastatic melanoma.

Early-phase trials and ongoing studies are focused on further confirming the clinical benefits of pembrolizumab in thoracic malignancies, highlighting its potential as a significant treatment option in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. Karim, S., Leighl, N.[2017]

Pembrolizumab (Keytruda) was approved by the FDA for treating metastatic non-small cell lung cancer (mNSCLC) in patients with tumors expressing PD-L1, showing significant improvements in overall survival (OS) and progression-free survival (PFS) in two major clinical trials with thousands of participants.

In the KEYNOTE-024 trial, pembrolizumab demonstrated a 40% reduction in the risk of death compared to chemotherapy, while in the KEYNOTE-010 trial, it also showed a significant survival advantage over chemotherapy in patients who had previously progressed on treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for Treatment of Metastatic Non-Small Cell Lung Cancer: First-Line Therapy and Beyond. Pai-Scherf, L., Blumenthal, GM., Li, H., et al.[2022]

Pembrolizumab (Keytruda) effectively blocks the PD-1 pathway, enhancing T-cell activity against tumors, which supports its role in promoting tumor regression and immune rejection.

Preclinical studies in cynomolgus monkeys showed that pembrolizumab has a favorable safety profile with no significant toxicological findings, aligning with its demonstrated safety and efficacy in human clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biophysical and Immunological Characterization and In Vivo Pharmacokinetics and Toxicology in Nonhuman Primates of the Anti-PD-1 Antibody Pembrolizumab. Hutchins, B., Starling, GC., McCoy, MA., et al.[2021]

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

Pembrolizumab is a monoclonal antibody that effectively blocks the PD-1 receptor on T cells, enhancing their ability to attack cancer cells, particularly in melanoma patients.

In a Phase I study involving 411 patients, pembrolizumab demonstrated high durable response rates with minimal toxicity, indicating its potential as a safe and effective treatment option for melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab joins the anti-PD-1 armamentarium in the treatment of melanoma. Hersey, P., Gowrishankar, K.[2017]

Citations

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A clinical study of MK-1484 to treat advanced solid tumors (MK ... MK-1484, the study medicine, is designed to treat advanced solid tumors. MK-1484 is an immunotherapy, which is a treatment that helps the immune ...

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A Study of MK-1484 as Monotherapy and in Combination With ... The purpose of this study is to assess the safety and tolerability and to establish a preliminary recommended Phase 2 dose (RP2D) of MK-1484 administered as ...

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Five-Year Outcomes With Pembrolizumab Versus ... Kaplan-Meier estimates of the 5-year OS rate were 31.9% for the pembrolizumab group and 16.3% for the chemotherapy group. Thirty-nine patients ...

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A Study of MK-1484 as Monotherapy and in Combination With ... The purpose of this study is to assess the safety and tolerability and to establish a preliminary recommended Phase 2 dose (RP2D) of MK-1484 ...

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