MK-6837 + Pembrolizumab for Cancer

Recruiting at 6 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Merck Sharp & Dohme LLC

Must be taking: Antiretroviral, HBV antivirals

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Cardiovascular disease, Active CNS metastases, others

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

Compensation: Varies

Number of Visits: 3

Duration: Up to approximately 59 months

168 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to assess the safety and initial effectiveness of a new treatment, MK-6837, for individuals with advanced or metastatic solid tumors unresponsive to standard treatments. It involves two groups: one receiving only MK-6837 and another receiving MK-6837 combined with pembrolizumab, a medicine that aids the immune system in fighting cancer. Individuals with advanced solid tumors who have not found success with other treatments might be suitable candidates. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot have received any systemic anticancer therapy or immunotherapy within 4 weeks before starting the study, and you should not be on chronic systemic steroid therapy or other immunosuppressive therapy within 7 days before the first dose.

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

Research has shown that MK-6837 remains in the early stages of human safety testing. Scientists are primarily assessing how well people tolerate this treatment and identifying any immediate side effects. Detailed safety information is not yet available because the studies are ongoing.

In contrast, pembrolizumab, the drug tested alongside MK-6837, has already received approval for other conditions. It has been shown to be safe for those uses, with known side effects such as tiredness and skin reactions. However, the safety profile may differ when combined with MK-6837, which current research aims to determine.

In this trial, participants will receive increasing doses of MK-6837, either alone or with pembrolizumab, to gather more information about safety and tolerance. Prospective participants should understand that early trials focus heavily on monitoring for potential side effects to ensure participant safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about MK-6837 for cancer because it offers a fresh approach by potentially enhancing the immune response against tumors. Unlike current standard treatments, which often focus on directly targeting cancer cells or using general immune checkpoint inhibitors like pembrolizumab alone, MK-6837 is designed to work in tandem with pembrolizumab to possibly boost the immune system's ability to fight cancer more effectively. This combination therapy could offer a more robust response by using MK-6837 to further activate the immune system, setting it apart from existing therapies.

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

Research has shown that pembrolizumab, part of the treatment in this trial, was effective and safe in previous studies involving 411 patients, making it a promising option for treating advanced cancers. Additionally, five-year research on pembrolizumab, also known as KEYTRUDA®, demonstrated a significant survival benefit when combined with chemotherapy for certain lung cancers. In this trial, some participants will receive MK-6837 alone, while others will receive a combination of MK-6837 and pembrolizumab. MK-6837, the new treatment being tested, is still under study. Researchers are examining its safety and early effectiveness both as a monotherapy and in combination with pembrolizumab. Overall, current data supports the potential of pembrolizumab, while MK-6837 remains under evaluation. ^{1 2 3 4 6}

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 people with advanced or metastatic solid tumors that haven't improved with standard treatments. It's open to those who have controlled HIV on medication, and those with a history of Hepatitis B or C if their viral load is undetectable. Participants must have confirmed solid tumor pathology reports.

Inclusion Criteria

I am HBsAg positive but have been on HBV therapy for 4 weeks with an undetectable viral load.

I had Hepatitis C but my viral load is now undetectable.

My cancer is confirmed to be advanced or has spread, based on a lab report.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive MK-6837 as monotherapy or in combination with pembrolizumab, with doses administered every 3 weeks until progressive disease or discontinuation

Up to approximately 59 months

Every 3 weeks (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• MK-6837
• Pembrolizumab

Trial Overview The study tests MK-6837 alone and combined with Pembrolizumab in treating advanced cancer. It aims to assess the safety, how well the body handles these drugs (pharmacokinetics), and initial effectiveness without any hypothesis testing.

How Is the Trial Designed?

Group I: Arm 2: MK-6837 + Pembrolizumab Combination Therapy Experimental Treatment 3 Interventions

Participants receive escalating doses of MK-6837 via IV infusion Q3W (Day 1 of every 21-day cycle) until progressive disease or discontinuation PLUS 200mg of pembrolizumab via IV infusion Q3W (Day 1 of every 21-day cycle) for up to 35 administrations (up to \~2 years).

Group II: Arm 1: MK-6837 Monotherapy Experimental Treatment 2 Interventions

Participants receive escalating doses of MK-6837 via intravenous (IV) infusion once every 3 weeks (Q3W) (Day 1 of every 21-day cycle) until progressive disease or discontinuation.

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 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]

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, a PD-1 inhibitor used in cancer treatment, can lead to rare but serious immune-related adverse events, including type 1 diabetes mellitus, occurring in about 0.2% of cases.

A review of 42 cases revealed that patients may develop diabetic ketoacidosis during treatment, highlighting the need for blood glucose monitoring and awareness of this potential side effect among clinicians.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. Clotman, K., Janssens, K., Specenier, P., et al.[2022]

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]

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, an immune checkpoint inhibitor, can cause pneumonitis in 1%-5% of patients, and this case report highlights an atypical presentation of this side effect in a patient with metastatic squamous cell carcinoma.

The patient was successfully treated with steroid therapy after ruling out other potential causes, leading to complete resolution of the pneumonitis, emphasizing the importance of recognizing and managing atypical cases of checkpoint inhibitor-pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. Jeon, WJ., Nguyen, J., Castillo, DR., et al.[2023]

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]

Citations

1. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/502796

A Study of MK-6837 as a Monotherapy and Combination ... The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary efficacy of MK-6837, administered as a monotherapy ...

2. withpower.com withpower.com/trial/phase-1-neoplasm-metastasis-6-2024-a1add

MK-6837 + Pembrolizumab for Cancer The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary efficacy of MK-6837, administered as a monotherapy ...

3. merckclinicaltrials.com merckclinicaltrials.com/trial/nct06460961/

A Study of MK-6837 as a Monotherapy and Combination ... The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary efficacy of MK-6837, administered as a monotherapy ...

4. connect.careboxhealth.com connect.careboxhealth.com/en-US/trial/listing/502796

A Study of MK-6837 as a Monotherapy and Combination ... The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary efficacy of MK-6837, administered as a monotherapy ...

5. merck.com merck.com/news/five-year-data-for-mercks-keytruda-pembrolizumab-plus-chemotherapy-showed-sustained-survival-benefit-versus-chemotherapy-alone-in-two-studies-for-metastatic-non-small-cell-lung-cancer-nsclc/

Five-Year Data for Merck's KEYTRUDA® (pembrolizumab ... Five-year overall survival rate of 19.4% and 18.4% for KEYTRUDA plus chemotherapy in KEYNOTE-189 and KEYNOTE-407, respectively.

6. msdclinicaltrials.com msdclinicaltrials.com/trial/nct06460961/?lang=en-au

A Study of MK-6837 as a Monotherapy and Combination ... The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary efficacy of MK-6837, administered as a monotherapy ...