MK-6598 + Pembrolizumab for Advanced Solid Cancers

No longer 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, others

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: 21

Duration: 24 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called MK-6598, both alone and in combination with pembrolizumab, to evaluate their effectiveness and safety in treating advanced solid cancers. Researchers aim to determine the best dose for future studies. Suitable participants have solid tumors that have spread and have not responded to other treatments. Individuals with such conditions may qualify for this trial. 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.

Do I have to stop taking my current medications to join the trial?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot have received prior systemic anticancer therapy within 4 weeks before the first dose of the study intervention, and you must not be on chronic systemic steroid therapy exceeding 10 mg daily of prednisone equivalent within 7 days before starting the study treatment. It's best to discuss your specific medications with the trial team.

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

Research shows that MK-6598 is a new treatment currently being tested for safety in people. Since it is in the early stages of testing, limited information exists on how well people tolerate it. This phase of the study focuses on assessing its safety and determining the right dose for future research.

Pembrolizumab, however, has undergone extensive testing in many studies and is already approved for treating some types of cancer. Research has shown that it is generally well-tolerated. Some people might experience mild to moderate side effects, but these are usually manageable.

Although MK-6598 is new, researchers are testing it in combination with pembrolizumab to evaluate their combined effects. The aim is to ensure this combination is safe before proceeding to larger studies. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about MK-6598 and its combination with pembrolizumab for advanced solid cancers because these treatments offer a novel approach compared to the standard options. Unlike typical treatments that mainly focus on targeting cancer cells directly, MK-6598 may work by modulating the immune system to better recognize and attack cancer cells, enhancing the effect of pembrolizumab, an existing immunotherapy. This potentially dual mechanism, involving both direct cancer cell targeting and immune modulation, could lead to more effective outcomes for patients with hard-to-treat solid tumors. Moreover, the ability to adjust MK-6598 dosage provides flexibility in treatment, aiming to optimize therapeutic benefits while managing side effects.

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

Research shows that MK-6598 can block a protein called IL4I1, but it is not very effective on its own against cancer. This suggests it might not serve well as a standalone cancer treatment. In this trial, some participants will receive MK-6598 alone, while others will receive a combination of MK-6598 with pembrolizumab, which might enhance the immune system's ability to fight cancer. Pembrolizumab alone has proven effective for various cancers, such as head and neck cancers, by aiding the immune system in attacking cancer cells. The goal of combining these treatments is to enhance pembrolizumab's effectiveness, although further research is needed to confirm this. Overall, this combination is under study to determine if it can offer a stronger treatment option for advanced cancers. ^{2 4 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?

Adults with advanced or metastatic solid tumors who've tried all other treatments can join this trial. They must have a tumor sample, measurable disease for assessment, and agree to biopsies. Women of childbearing potential and men must follow strict contraception guidelines. People with HIV can join if it's well-controlled.

Inclusion Criteria

I agree to use contraception and not donate sperm for 102 days after the study if I join.

I have at least one cancerous lesion that can be biopsied twice.

My advanced cancer is confirmed by tests and I've tried or can't tolerate all known beneficial treatments.

Exclusion Criteria

I have not had radiotherapy in the last 2 weeks, nor do I need steroids for radiation side effects.

I stopped a cancer immunotherapy due to a severe side effect.

I have an immune system disorder or have been on high-dose steroids or other immune-weakening medicines recently.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive MK-6598 daily at escalating dose levels from 50-500 mg, with or without pembrolizumab, for up to 35 cycles

24 months

Visits every 21 days per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

What Are the Treatments Tested in This Trial?

Interventions

• MK-6598
• Pembrolizumab

Trial Overview

The study is testing MK-6598 alone and combined with Pembrolizumab in adults with advanced solid tumors to find the safest dose that works best (RP2D). Participants will be assessed for how their tumors respond to these treatments.

How Is the Trial Designed?

Group I: MK-6598 + Pembrolizumab Experimental Treatment 2 Interventions

Participants will receive MK-6598 QD at escalating dose levels from 50-500, plus pembrolizumab 200 mg once every 21-day cycle for up to 35 cycles (up to approximately 24 months).

Group II: MK-6598 Experimental Treatment 1 Intervention

Participants will receive MK-6598 daily (QD) at escalating dose levels from 50-500 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, an immune checkpoint inhibitor for non-small cell lung carcinoma, has been linked to adverse renal outcomes, including acute kidney injury.

In a reported case, a patient developed acute tubulointerstitial nephritis after starting pembrolizumab, and while renal function improved with long-term corticosteroid treatment after discontinuation of the drug, it only improved partially.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute Tubulointerstitial Nephritis: A Case Report on Rare Adverse Effect of Pembrolizumab. Basnet, S., Dhital, R., Tharu, B.[2020]

Pembrolizumab significantly improved progression-free survival (PFS) in patients with unresectable or metastatic microsatellite instability-high (MSI-H) colorectal cancer, with a median PFS of 16.5 months compared to 8.2 months for standard chemotherapy, indicating its efficacy as a first-line treatment.

The FDA found no safety concerns during the approval process, and while both pembrolizumab and standard of care had similar adverse reactions, the duration of treatment with pembrolizumab was nearly double that of standard care, suggesting a potentially more favorable treatment profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for the First-line Treatment of Patients with MSI-H/dMMR Advanced Unresectable or Metastatic Colorectal Carcinoma. Casak, SJ., Marcus, L., Fashoyin-Aje, L., et al.[2022]

In a phase 1a/b trial involving 26 patients with PD-L1-positive non-small cell lung cancer (NSCLC), the combination of ramucirumab and pembrolizumab showed a manageable safety profile, with 84.6% experiencing treatment-related adverse events, primarily hypertension.

The treatment demonstrated promising efficacy, with an objective response rate of 42.3%, and particularly strong results in patients with high PD-L1 expression (TPS ≥ 50%), who had a median progression-free survival that was not reached.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 Expansion Cohort of Ramucirumab Plus Pembrolizumab in Advanced Treatment-Naive NSCLC. Herbst, RS., Arkenau, HT., Bendell, J., et al.[2023]

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 (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]

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, 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]

In the KEYNOTE-024 study involving 305 patients with untreated advanced non-small-cell lung cancer, pembrolizumab significantly improved overall survival (OS) compared to platinum-based chemotherapy, with a median OS of 30.0 months versus 14.2 months for chemotherapy.

Pembrolizumab also had a better safety profile, with fewer treatment-related severe adverse events (31.2% for pembrolizumab vs. 53.3% for chemotherapy), indicating it is a safer option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Updated Analysis of KEYNOTE-024: Pembrolizumab Versus Platinum-Based Chemotherapy for Advanced Non-Small-Cell Lung Cancer With PD-L1 Tumor Proportion Score of 50% or Greater. Reck, M., Rodríguez-Abreu, D., Robinson, AG., 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]

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These data suggest that despite its ability to inhibit IL4I1 protein, MK-6598 has limited antitumor activity as monotherapy or in combination ...

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A Study of MK-6598 as Monotherapy and in Combination With ...

The purpose of this study is to assess the efficacy and safety and establish a preliminary recommended Phase 2 dose (RP2D) of MK-6598 administered as ...

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The first trial of pembrolizumab was performed in patients with advanced solid tumors and showed that the drug was safe at all dose levels tested (1, 3 and 10 ...

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An open, multicenter phase I study to evaluate the safety, ...

This study investigates a novel substance (MK-6598) that has never been tested in humans, either alone or in combination with an approved medication, and aims ...