MK-0482 + Pembrolizumab for Advanced Cancer

No longer recruiting at 18 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Merck Sharp & Dohme Corp.

Must not be taking: Immunotherapy, Corticosteroids

Disqualifiers: Second malignancy, CNS metastases, others

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

Compensation: Varies

Number of Visits: 42

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores new treatments for advanced cancers lacking other options. It has two parts: the first tests the safety and optimal dose of a new drug, MK-0482 (an experimental treatment), both alone and with pembrolizumab. The second part examines the effectiveness of the MK-0482 and pembrolizumab combination, with and without chemotherapy, for specific advanced cancers such as breast, pancreatic, and lung cancer. Individuals with hard-to-treat cancers who have not responded to other treatments might be suitable candidates for this trial. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the chance to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, certain medications, like strong or moderate inhibitors and inducers of specific enzymes, may need to be discontinued. It's best to discuss your current medications with the trial team.

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

Research has shown that MK-0482, whether used alone or with pembrolizumab, is generally well-tolerated. Early studies found that patients with advanced solid tumors did not experience severe side effects from these treatments. Pembrolizumab, already used for many types of cancer, typically causes mild and manageable side effects.

When combined with pembrolizumab and other drugs like paclitaxel or gemcitabine, MK-0482 maintains an acceptable safety profile. For instance, pembrolizumab with paclitaxel has demonstrated a good safety record in patients with triple-negative breast cancer. Similarly, combining it with gemcitabine and nab-paclitaxel for pancreatic cancer has proven safe in trials.

For conditions like glioblastoma and soft tissue sarcoma, adding MK-0482 to pembrolizumab has not led to unexpected safety issues. The treatment generally follows the known safety patterns of pembrolizumab.

In summary, MK-0482 and pembrolizumab, whether used alone or together, are mostly well-tolerated. Side effects can occur, but they are typically manageable, offering hope for those considering joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about MK-0482 and pembrolizumab because these treatments offer a promising approach to tackling advanced cancers. Unlike standard chemotherapy, which attacks rapidly dividing cells indiscriminately, MK-0482 is a novel agent being studied for its potential to precisely target cancer cells. Pembrolizumab is an immunotherapy that helps the immune system recognize and fight cancer cells more effectively. Together, these drugs may enhance the body's ability to combat cancer by combining a targeted treatment with immune system activation, potentially offering better outcomes and fewer side effects than traditional treatments.

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

Research has shown that MK-0482, one of the treatments in this trial, can slow cancer growth in some patients with advanced solid tumors when used alone. In this trial, some participants will receive MK-0482 combined with pembrolizumab, a treatment proven effective in various cancers, such as non-small cell lung cancer. Pembrolizumab enhances the immune system's ability to attack cancer cells. For participants with triple-negative breast cancer, the trial includes adding paclitaxel to increase effectiveness. In non-small cell lung cancer, similar combinations with pembrolizumab and chemotherapy have improved survival rates. Overall, early studies suggest these combinations could offer new hope for people with advanced cancers. ^{1 2 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?

This trial is for adults with advanced solid tumors and no remaining treatment options. Specific groups include those with certain types of brain cancer, pancreatic cancer, soft tissue sarcoma, lung cancer, or triple negative breast cancer. Participants must have measurable disease, provide a tumor sample, meet organ function criteria and performance status requirements. Women of childbearing potential must use effective contraception.

Inclusion Criteria

I have metastatic pancreatic cancer, haven't had treatment for it, and my albumin level is at least 3.0 g/dL.

I have triple negative breast cancer that has returned or spread, not treated before for this stage, and my tumor is PD-L1 positive.

My organs are functioning well.

Exclusion Criteria

I have not had active treatment for another cancer, except for certain skin, bladder cancers, or in situ cancers, in the last 2 years.

I am currently being treated for an infection.

My cancer has spread to my brain or the membranes around my brain.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Part 1 involves dose escalation to determine the safety and tolerability and to establish a preliminary recommended Phase 2 dose (RP2D) of MK-0482 as monotherapy and in combination with pembrolizumab.

Up to 24 months

Every 21 days (Q3W) for up to 35 cycles

Expansion Cohort

Part 2 involves expansion cohorts to determine safety and tolerability of MK-0482 in combination with pembrolizumab with and without chemotherapy in participants with advanced tumor-specific cohorts.

Up to 24 months

Every 21 days (Q3W) for up to 35 cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Gemcitabine
• MK-0482
• Nab-paclitaxel
• Paclitaxel
• Pembrolizumab
• Pemetrexed

Trial Overview The study tests MK-0482 alone and combined with pembrolizumab in two parts: dose escalation to find the safest dose (Part 1), followed by expansion cohorts to assess safety and effectiveness in specific cancers when combined with pembrolizumab and chemotherapy (Part 2).

How Is the Trial Designed?

Group I: Part 2: Cohort E Experimental Treatment 4 Interventions

Participants with metastatic non-squamous non-small cell lung carcinoma (NSCLC) (1L) receive MK-0482 via IV infusion plus pembrolizumab 200 mg via IV infusion plus Pemetrexed 500 mg/m\^2 via IV infusion on Day 1 of each 21-day cycle (Q3W) up to 35 administrations (up to approximately 2 years) plus carboplatin with desired dose of area under the curve (AUC) 5 and pemetrexed 500 mg/m\^2, both administered via IV infusion, followed by maintenance therapy with pemetrexed 500 mg/m\^2 via IV infusion for up to a total of 35 administrations (up to approximately 2 years).

Group II: Part 2: Cohort D Experimental Treatment 2 Interventions

Participants with metastatic soft tissue sarcoma (STS) (2L) receive MK-0482 via IV infusion plus pembrolizumab 200 mg via IV infusion on Day 1 of each 21-day cycle (Q3W) up to 35 administrations (up to approximately 2 years).

Group III: Part 2: Cohort C Experimental Treatment 4 Interventions

Participants with metastatic pancreatic ductal adenocarcinoma (PDAC) (1L) receive MK-0482 via IV infusion plus pembrolizumab 200 mg via IV infusion on Day 1 of each 21-day cycle (Q3W) up to 35 administrations (up to approximately 2 years), Nab-Paclitaxel 125 mg/m\^2 via IV infusion and gemcitabine 1000 mg/m\^2 via IV infusion until PD or unacceptable toxicity that requires discontinuation.

Group IV: Part 2: Cohort B Experimental Treatment 2 Interventions

Participants with recurrent non-operable glioblastoma (GBM) current treatment of second line (2L) receive MK-0482 via IV infusion plus pembrolizumab 200 mg via IV infusion on Day 1 of each 21-day cycle (Q3W) up to 35 administrations (up to approximately 2 years).

Group V: Part 2: Cohort A Experimental Treatment 3 Interventions

Participants with metastatic triple negative breast cancer (TNBC) first line treatment (1L) receive MK-0482 via IV infusion plus pembrolizumab 200 mg via IV infusion on Day 1 of each 21-day cycle (Q3W) up to 35 administrations (up to approximately 2 years) and paclitaxel 90 mg/m\^2 via IV infusion until PD or discontinuation.

Group VI: Part 1: MK-0482 Monotherapy Experimental Treatment 1 Intervention

Participants receive escalating doses of MK-0482 via intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) for up to 35 administrations (up to approximately 2 years).

Group VII: Part 1: MK-0482 + Pembrolizumab Combination Therapy Experimental Treatment 2 Interventions

Participants receive escalating doses of MK-0482 via IV infusion + pembrolizumab 200 mg via IV infusion on Day 1 of each 21-day cycle (Q3W) for up to 35 administrations (up to approximately 2 years).

Who Is Running the Clinical Trial?

Merck Sharp & Dohme Corp.

Lead Sponsor

Trials

2,287

Recruited

4,582,000+

Chirfi Guindo

Merck Sharp & Dohme Corp.

Chief Medical Officer

Engineering degree from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme Corp.

Chief Executive Officer since 2021

J.D. from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

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

In a study of 24 patients with advanced non-small cell lung cancer (NSCLC) treated with pembrolizumab, the objective response rate was 45.8%, indicating that nearly half of the patients experienced a reduction in tumor size after treatment.

Pembrolizumab showed promising results even in PD-L1-negative patients, with a major pathological response of 75% and a pathological complete response of 50% in those who underwent surgery, suggesting its potential effectiveness across different patient profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of pembrolizumab for the treatment of advanced non-small cell lung cancer: a retrospective, single-centre, single-arm study. Guo, T., Ding, Y., Chen, L., et al.[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) 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, 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 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, 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]

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 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]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.4139

Phase 1 study of anti–immunoglobulin-like transcript 3 ... Conclusions: MK-0482 + pembrolizumab + Gem/Nab-P showed a manageable AE profile in patients with treatment-naive mPDAC, which was generally ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03918278

A Study of MK-0482 as Monotherapy and in Combination ... This is a 2 part study. Part 1 is a dose escalation to determine the safety and tolerability and to establish a preliminary recommended Phase 2 dose (RP2D) ...

3. researchgate.net researchgate.net/publication/381492718_Phase_1_study_of_anti-immunoglobulin-like_transcript_3_ILT3_monoclonal_antibody_MK-0482_pembrolizumab_gemcitabine_nab-paclitaxel_GemNab-P_in_patients_pts_with_metastatic_pancreatic_ductal_adenocarcino

Phase 1 study of anti–immunoglobulin-like transcript 3 ... Conclusions: MK-0482 + pembrolizumab + Gem/Nab-P showed a manageable AE profile in patients with treatment-naive mPDAC, which was generally consistent with the ...

4. asco.org asco.org/posters/POSTER239193

Phase 1 study of anti–immunoglobulin-like transcript 3 ... Phase 1 study of anti–immunoglobulin-like transcript 3 (ILT3) monoclonal antibody MK-0482 + pembrolizumab + gemcitabine + nab-paclitaxel (Gem/Nab-P) in patients ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/29119276/

Phase Ib/II study of gemcitabine, nab-paclitaxel, and ... A single center phase Ib/II study of gemcitabine, nab-paclitaxel, and pembrolizumab (GNP) to evaluate the safety and efficacy in metastatic pancreatic ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT07076121

NCT07076121 | A Study Comparing BMS-986504 in ... The purpose of this study is to assess the safety and efficacy of BMS-986504, a selective, MTA-cooperative PRMT5 inhibitor, in combination with ...

7. therivabio.com therivabio.com/press_releases/theriva-biologics-announces-primary-endpoints-for-efficacy-and-safety-achieved-in-virage-phase-2b-clinical-trial-of-vcn-01-with-gemcitabine-nab-paclitaxel-in-newly-diagnosed-metastatic-pancre/

Theriva™ Biologics Announces Primary Endpoints for ... Pancreatic ductal adenocarcinoma (“PDAC”) accounts for more than 90% of all pancreatic tumors. It can be located either in the head of the ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT04787991

Study Details | NCT04787991 | Exploratory Platform Trial to ... This is an open-label, non-randomized, exploratory platform trial designed to assess the safety and antitumor activity of immunotherapy, in combination with ...