MK-1088 + Pembrolizumab for Cancer

No longer recruiting at 16 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Merck Sharp & Dohme LLC

Must not be taking: Steroids, Corticosteroids

Disqualifiers: CNS metastases, Active infection, Autoimmune disease, Cardiovascular disease, others

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

Compensation: Varies

Number of Visits: 21

Duration: up to 24 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment, MK-1088, both alone and with pembrolizumab (KEYTRUDA), to determine its effectiveness in shrinking advanced solid tumors unresponsive to standard treatments. The trial aims to assess the safety, tolerability, and pharmacokinetics of MK-1088. It seeks participants with advanced cancers that have not improved with current therapies. For those who have tried other cancer treatments without success, this trial may be suitable. 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.

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 must not have had chemotherapy, radiation, or biological cancer therapy within 4 weeks before starting the study, and you should not have received a live vaccine within 30 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-1088 has been tested for safety and tolerability. In early studies, most participants tolerated MK-1088 well, experiencing manageable side effects such as mild headaches and tiredness.

When combined with pembrolizumab, it is important to note that pembrolizumab is already approved for treating other cancers and is generally less harmful than many chemotherapy treatments. However, it can cause serious issues like lung inflammation in a small number of people.

This trial is in its early stages, focusing primarily on assessing the safety of the treatments. While some early information is available, a complete understanding of safety will develop as more participants join the trial and more data is collected. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

MK-1088 is unique because it offers a different approach to treating advanced solid tumors by potentially enhancing the immune response against cancer cells. Unlike many current therapies that focus on directly attacking cancer cells, MK-1088 works by modulating the immune system. When combined with pembrolizumab, a well-known immune checkpoint inhibitor, it may enhance the body's ability to identify and destroy cancer cells more effectively. Researchers are excited because this combination could lead to improved outcomes and offer a new lifeline for patients who don't respond well to existing treatments.

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

Research has shown that MK-1088, a new drug tested for advanced solid tumors, significantly reduced tumors in animal studies, such as those with mice. This suggests it might also shrink tumors in people. In this trial, some participants will receive MK-1088 alone, while others will receive it in combination with pembrolizumab. Pembrolizumab, another drug, has already been shown to help treat various cancers by aiding the immune system in fighting cancer cells. It has improved survival rates in patients with non-small cell lung cancer and melanoma. The combination of MK-1088 with pembrolizumab is under study because pembrolizumab boosts the immune system, potentially enhancing MK-1088's effectiveness in shrinking tumors. ^{1 2 3 6 7}

Who Is on the Research Team?

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Are You a Good Fit for This Trial?

Inclusion Criteria

If human immunodeficiency virus (HIV) positive, has well-controlled HIV on anti-retroviral therapy (ART)

You have been diagnosed with an advanced or metastatic solid tumor, and have either received, had issues with, or were not eligible for a treatment that is known to provide clinical benefit.

For metastatic castrate-resistant prostate cancer (mCRPC) only: (1) Must have previously received docetaxel, prior treatment with one other chemotherapy is allowed as well as up to 2 second-generation hormonal manipulations and (2) have prostate cancer progression within 6 months before screening, as determined by the investigator

Exclusion Criteria

You have had another type of cancer in the past, but it's okay if it has been treated completely and there has been no sign of it for at least 2 years.

You have a stomach or liver condition that could affect how your body absorbs or processes oral medications.

Has had chemotherapy, definitive radiation, or biological cancer therapy within 4 weeks (2 weeks for palliative radiation) before the first dose of study intervention

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive MK-1088 as monotherapy or in combination with pembrolizumab for up to 35 cycles

up to 24 months

21-day cycles with regular visits

Dose-limiting Toxicity Evaluation

Evaluation of dose-limiting toxicity during the initial treatment period

21 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to 13 months

What Are the Treatments Tested in This Trial?

Interventions

• MK-1088
• Pembrolizumab

How Is the Trial Designed?

Group I: MK-1088 600 mg Experimental Treatment 1 Intervention

Participants received MK-1088 (QD) orally at 600 mg on days 1-21 of each 21-day cycle for up to 35 cycles (up to \~24 months)

Group II: MK-1088 400 mg Experimental Treatment 1 Intervention

Participants received MK-1088 (QD) orally at 400 mg on days 1-21 of each 21-day cycle for up to 35 cycles (up to \~24 months)

Group III: MK-1088 200 mg + Pembrolizumab Experimental Treatment 2 Interventions

Participants received MK-1088 daily (QD) orally at 200 mg on days 1-21 of each 21-day cycle plus pembrolizumab at 200 mg intravenous (IV) infusion every 3 weeks (Q3W), on Day 1 of each 21-day cycle for up to 35 cycles (up to \~24 months)

Group IV: MK-1088 200 mg Experimental Treatment 1 Intervention

Participants received MK-1088 (QD) orally at 200 mg on days 1-21 of each 21-day cycle for up to 35 cycles (up to \~24 months)

Group V: MK-1088 100 mg + Pembrolizumab Experimental Treatment 2 Interventions

Participants received MK-1088 daily (QD) orally at 100 mg on days 1-21 of each 21-day cycle plus pembrolizumab at 200 mg intravenous (IV) infusion every 3 weeks (Q3W), on Day 1 of each 21-day cycle for up to 35 cycles (up to \~24 months)

Group VI: MK-1088 100 mg Experimental Treatment 1 Intervention

Participants received MK-1088 daily (QD) orally at 100 mg on days 1-21 of each 21-day cycle for up to 35 cycles (up to \~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 (MK-3475) is a monoclonal antibody that blocks PD-1, which helps the immune system fight cancer by preventing tumor cells from evading immune responses; it has shown high tumor response rates in advanced melanoma and non-small cell lung cancer.

The drug received accelerated FDA approval due to its effectiveness in early clinical trials, demonstrating long-lasting effects in patients who had previously been treated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab: PD-1 inhibition as a therapeutic strategy in cancer. McDermott, J., Jimeno, A.[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]

In a study of 88 advanced melanoma patients treated with pembrolizumab, 81.8% experienced any-grade toxicities, with skin and gastrointestinal issues being the most common side effects.

Despite the high incidence of side effects, pembrolizumab was found to be well tolerated in real-world settings, and severe toxicities were manageable with systemic steroids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world experience with pembrolizumab toxicities in advanced melanoma patients: a single-center experience in the UK. So, AC., Board, RE.[2022]

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) is the first anti-PD-1 therapy approved in the US for treating advanced malignant melanoma, specifically for patients who have progressed after prior treatments.

It is designed to target the PD-1 protein, enhancing the immune system's ability to fight cancer, and is currently under review for approval in the EU.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab: first global approval. Poole, RM.[2021]

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]

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, 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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11625052/

A randomized phase 1 study of safety, tolerability, and ... The results show that single ascending doses of MK-1088 are well tolerated up to 224 mg in healthy male adults with no serious AEs or deaths ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05394350

A Study of MK-1088 as Monotherapy and in Combination ... Efficacy data from participants who experienced disease progression in the monotherapy arm and crossed over into the combination arm will be summarized in their ...

3. clinicaltrials.eu clinicaltrials.eu/inn/mk-1088/

Mk-1088 – Application in Therapy and Current Clinical ... MK-1088 is a new drug being studied for the treatment of advanced solid tumors. It is currently undergoing clinical trials to evaluate its safety, effectiveness ...

4. withpower.com withpower.com/trial/phase-2-neoplasms-5-2022-e448d

A Study of MK-1088 as Monotherapy and in Combination ... Pembrolizumab (Keytruda) has been shown to be effective in treating various cancers, including non-small cell lung cancer and melanoma, by helping the immune ...

5. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/50/NCT05394350/Prot_SAP_000.pdf

Official Protocol Title: NCT number: Document Date: Internal preclinical data show that MK-1088 administration led to significant antitumor efficacy as a single agent in the mouse syngeneic CT26 ...

6. researchgate.net researchgate.net/publication/383023336_A_randomized_phase_1_study_of_safety_tolerability_and_pharmacokinetics_of_MK-1088_a_novel_dual_adenosine_receptor_antagonist_in_healthy_adult_participants

A randomized phase 1 study of safety, tolerability, and ... This phase 1 first-in-human study evaluated the safety, tolerability, and pharmacokinetics of MK-1088, a novel, small-molecule dual inhibitor of ...

7. delta.larvol.com delta.larvol.com/Products/?ProductId=39a34df1-72d8-41a9-b725-929542f018a7

MK-1088 / Merck (MSD) A randomized phase 1 study of safety, tolerability, and pharmacokinetics of MK-1088, a novel dual adenosine receptor antagonist, in healthy adult ...