A Study of MK-1088 as Monotherapy and in Combination With Pembrolizumab in Participants With Advanced Solid Tumors (MK-1088-002)

Recruiting at 14 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

27 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a new drug, MK-1088, alone and with another cancer drug, pembrolizumab, in patients with advanced solid tumors who haven't responded to standard treatments. It aims to see if MK-1088 is safe, tolerable, and effective in shrinking tumors. Pembrolizumab has shown efficacy in multiple cancer types.

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.

What data supports the effectiveness of the drug MK-1088, Pembrolizumab, KEYTRUDA, MK-3475?

Pembrolizumab (Keytruda) has been shown to be effective in treating various cancers, including non-small cell lung cancer and melanoma, by helping the immune system attack cancer cells. It has been approved by the FDA for certain types of lung cancer and melanoma, demonstrating significant improvements in survival compared to chemotherapy. ^{1 2 3 4 5}

What safety data exists for pembrolizumab (Keytruda)?

Pembrolizumab (Keytruda) is generally considered less toxic than chemotherapy, but it can cause serious side effects like pneumonitis (lung inflammation) in 1%-5% of patients and type 1 diabetes in 0.2% of cases. These side effects are rare but important to consider when evaluating its safety. ^{4 5 6 7 8}

How is the drug MK-1088 with Pembrolizumab different from other treatments?

Pembrolizumab is unique because it is a PD-1 inhibitor that helps the immune system recognize and attack cancer cells by blocking a pathway that tumors use to hide from immune cells. This mechanism is different from traditional chemotherapy, which directly targets and kills cancer cells, and it has shown effectiveness in treating various cancers, including non-small cell lung cancer and melanoma. ^{3 4 5 6 9}

Research Team

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Eligibility Criteria

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

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

Treatment Details

Interventions

• MK-1088
• Pembrolizumab

Participant Groups

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

Findings from Research

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]

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, 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, 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 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 (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]

References

1. England pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for Treatment of Metastatic Non-Small Cell Lung Cancer: First-Line Therapy and Beyond. [2022]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Pembrolizumab: first global approval. [2021]

3. United States 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. [2021]

4. Ireland pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]

6. England pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. [2023]

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

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. [2022]

8. England pubmed.ncbi.nlm.nih.gov

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

9. Spain pubmed.ncbi.nlm.nih.gov

Pembrolizumab: PD-1 inhibition as a therapeutic strategy in cancer. [2017]