Immunotherapy for Cancer

Recruiting at 36 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Merck Sharp & Dohme Corp.

Must not be taking: Immunosuppressants, Steroids, Monoclonal antibodies

Disqualifiers: Immunodeficiency, Autoimmune disease, CNS metastases, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 2 years

1609 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests pembrolizumab, an immunotherapy drug, for individuals with advanced solid tumors unresponsive to standard treatments. The trial aims to determine if pembrolizumab can slow or stop tumor growth. Participants will receive either 400 mg or 200 mg doses of pembrolizumab. Suitable candidates for this trial have advanced cancers, such as anal, biliary, or thyroid tumors, that have progressed despite prior treatments. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot be on systemic steroid therapy or any immunosuppressive therapy 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 has shown that pembrolizumab, the treatment being tested, was well-tolerated in past studies on various advanced solid tumors. These studies indicate that pembrolizumab is generally safe, with manageable side effects. Common side effects include fatigue, itching, and loss of appetite.

In earlier trials, patients received pembrolizumab in different doses and tolerated it for extended periods. Notably, the FDA has already approved pembrolizumab for other conditions, indicating that its safety is well-understood and generally considered acceptable.

Prospective participants can feel reassured that pembrolizumab has been used safely in many different situations. However, as with any treatment, individual experiences can vary. It's important to discuss any concerns with the trial team or a healthcare provider. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about pembrolizumab for cancer treatment because it harnesses the power of immunotherapy, a groundbreaking approach that uses the body's immune system to fight cancer. Unlike traditional treatments like chemotherapy, which directly target cancer cells but can also harm healthy cells, pembrolizumab targets the PD-1 pathway. This helps unleash the immune system to recognize and attack cancer cells more effectively. Additionally, the two dosing regimens—400 mg every six weeks or 200 mg every three weeks—offer flexibility, potentially improving convenience and quality of life for patients with advanced solid tumors.

What is the effectiveness track record for pembrolizumab in treating advanced solid tumors?

Research has shown that pembrolizumab, a type of immunotherapy, holds promise for treating advanced solid tumors, particularly those with a high number of genetic changes (TMB-H). Real-world studies have confirmed its effectiveness in patients with these tumors. In some cases, pembrolizumab has extended patients' lives. However, for certain tumors, such as those that are microsatellite-stable with TMB-H, the benefits might be less significant. Overall, pembrolizumab aids the immune system in identifying and attacking cancer cells, offering hope for patients who haven't responded to other treatments. Participants in this trial will receive either 400 mg every 6 weeks or 200 mg every 3 weeks, depending on their assigned treatment arm. ^{1 5 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 that have worsened after standard treatments. They must have a specific type of tumor, be able to provide tissue samples, and have measurable disease. Participants should be relatively active (ECOG 0 or 1), expected to live at least 3 months, and have good organ function. Women who can bear children must use contraception.

Inclusion Criteria

My cancer is confirmed by lab tests and is an advanced solid tumor.

My cancer has worsened or I can't tolerate my current treatment.

I can provide a sample of my tumor for the study.

Exclusion Criteria

I haven't had cancer treatment or still have side effects from the last one within the past 2 weeks.

I have or had lung inflammation that needed steroids.

I haven't taken steroids or immunosuppressants in the last 7 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pembrolizumab 400 mg every 6 weeks or 200 mg every 3 weeks for up to 2 years

Up to 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to approximately 10.5 years

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab

Trial Overview The study tests pembrolizumab in patients with various unresectable or metastatic solid tumors that haven't responded well to existing therapies. The goal is to see how effective this drug is on different types of cancer by monitoring the participants' responses.

How Is the Trial Designed?

Group I: Pembrolizumab 400 mg Experimental Treatment 1 Intervention

Participants with any advanced solid tumor that has failed at least one line of therapy and is Tumor- Mutational Burden-High (TMB-H), excluding participants with mismatch repair deficient (dMMR/MSI-H) tumors. The dosing regimen for this cohort will be 400 mg every 6 weeks (Q6W) for up to 18 administrations (up to approximately 2 years of treatment).

Group II: Pembrolizumab 200 mg Experimental Treatment 1 Intervention

Participants will receive pembrolizumab 200 mg intravenously on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years of treatment).

Pembrolizumab is already approved in United States, European Union, United Kingdom for the following indications:

Approved in United States as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in European Union as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in United Kingdom as KEYTRUDA for:

• Untreated metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1

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

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, 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]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating unresectable or metastatic melanoma based on two clinical trials involving 1,374 patients, showing significant improvements in overall survival compared to ipilimumab, with hazard ratios indicating a reduced risk of death.

Patients receiving pembrolizumab also experienced significant improvements in progression-free survival, although some immune-mediated adverse reactions like hypothyroidism and pneumonitis were noted, highlighting the importance of monitoring for side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. Barone, A., Hazarika, M., Theoret, MR., 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]

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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38451314/

Clinical evidence for efficacy of pembrolizumab in MSI-H ... Our retrospective study evaluated the clinical efficacy and safety of pembrolizumab in treating advanced solid tumors with either MSI-H or TMB-H.

2. catalogues.ema.europa.eu catalogues.ema.europa.eu/node/4443/methodological-aspects

Real-world effectiveness of pembrolizumab among patients ... The main objective of the study is to describe real-world effectiveness of pembrolizumab among patients with advanced solid tumors with TMB-H ...

3. esmoopen.com esmoopen.com/article/S2059-7029(24)01879-9/fulltext

Efficacy of pembrolizumab in microsatellite-stable, tumor ... Pembrolizumab showed significantly shorter survival than FTD/TPI (±bevacizumab) in later-line treatment of MSS-TMB-H mCRC. •. Comprehensive ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT01295827

NCT01295827 | Study of Pembrolizumab (MK-3475) in ... The study will investigate the safety, tolerability, and efficacy of pembrolizumab (2 mg/kg and 10 mg/kg) in participants with advanced or metastatic MEL.

5. nature.com nature.com/articles/s41467-025-59615-3

Long-Term Efficacy of Pembrolizumab and the Clinical ... Outcomes of patients with all locally advanced dMMR/MSI-H solid tumors. The 3-year EFS and OS rates for all 35 patients were 80% (95% CI: 66–93 ...

6. merck.com merck.com/product/usa/pi_circulars/k/keytruda/keytruda_pi.pdf

keytruda_pi.pdf The safety of KEYTRUDA for the treatment of patients with locally advanced or metastatic urothelial ... or MSI-H solid tumors received KEYTRUDA 2 mg/kg every 3 ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/25977344/

Phase I Study of Pembrolizumab (MK-3475; Anti-PD-1 ... Conclusions: Pembrolizumab was well tolerated and associated with durable antitumor activity in multiple solid tumors. The lowest dose with full ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT02054806

NCT02054806 | Study of Pembrolizumab (MK-3475) in ... This study will assess the efficacy and safety of pembrolizumab (MK-3475) administered to participants with incurable advanced biomarker-positive solid tumors.