Pembrolizumab for Lymphoma

Recruiting at 27 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Merck Sharp & Dohme Corp.

Must not be taking: Steroids, Monoclonal antibodies

Disqualifiers: Organ transplant, Cardiovascular disease, Autoimmune, 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: 18

Duration: 108 weeks

66 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

The primary objective of the study is to evaluate the objective response rate (ORR), by cohort, rrcHL and rrPMBCL, as assessed by the investigator according to Lugano classification criteria 2014 in participants treated with pembrolizumab every six weeks (Q6W).

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop your current medications. However, you cannot be on certain treatments like systemic steroids above a specific dose or have had recent treatments like monoclonal antibodies or radiotherapy. It's best to discuss your current medications with the trial team.

Is pembrolizumab generally safe for humans?

Pembrolizumab (also known as Keytruda or MK-3475) is generally considered safe, but it can cause some immune-related side effects. These include rare cases of type 1 diabetes (a condition where the body can't produce insulin) and pneumonitis (inflammation of the lungs), which can be serious. Other common side effects include fatigue, cough, nausea, and skin rash. ^{1 2 3 4 5}

How is the drug Pembrolizumab different from other treatments for lymphoma?

Pembrolizumab is unique because it works by blocking a protein called PD-1, which helps the immune system recognize and attack cancer cells, unlike other treatments like Rituximab that target specific antigens on cancer cells directly. ^{6 7 8 9 10}

What data supports the effectiveness of the drug pembrolizumab for treating lymphoma?

Pembrolizumab has shown significant effectiveness in treating Hodgkin Lymphoma and has demonstrated promising responses in some subtypes of non-Hodgkin Lymphoma that share genetic features with Hodgkin Lymphoma. Additionally, it has shown promising activity in relapsed or difficult-to-treat extranodal NK/T-cell lymphoma. ^{1 2 11 12 13}

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 specific types of lymphoma (cHL or PMBCL) that have come back or didn't respond to treatment. They should be fairly healthy, able to perform daily activities with ease or only limited help, and not pregnant or breastfeeding. Participants need measurable disease, may have had certain prior treatments but not others like CAR-T therapy, and must not have serious heart issues or active infections.

Inclusion Criteria

- Is not a woman of child bearing potential (WOCBP). OR

My cancer can be measured on scans and has a large enough lesion that hasn't been treated with radiation.

I am using effective birth control or have been abstinent, and will continue for 120 days after the study ends.

Exclusion Criteria

You have a severe allergic reaction (Grade 3 or higher) to pembrolizumab or any of its ingredients.

I have received CAR-T cell therapy before.

I have had a serious heart condition or stroke in the last 6 months.

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 intravenously every 6 weeks, up to 18 doses

108 weeks

18 visits (in-person, every 6 weeks)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to approximately 54 months

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab

Trial Overview The study tests Pembrolizumab given every six weeks to see how well it works against two kinds of lymphoma. The main goal is to check the percentage of patients whose cancer shrinks or disappears after treatment as judged by a set standard called Lugano classification criteria.

How Is the Trial Designed?

Group I: Arm 1 Experimental Treatment 1 Intervention

Pembrolizumab (MK-3475), 400 mg, Q6W, intravenous (IV) infusion, Day 1 then Q6W up to 18 doses.

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, a monoclonal antibody targeting PD-1, has shown significant clinical efficacy in treating Hodgkin Lymphoma and promising early results in certain subtypes of Non-Hodgkin Lymphoma, particularly those with genetic similarities to HL.

Current data suggest that pembrolizumab has a favorable safety profile and efficacy as a single agent in treating diffuse large B cell lymphomas, with future strategies likely to focus on biomarker-driven approaches and combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of diffuse large B-cell lymphoma. Sheikh, S., Kuruvilla, J.[2020]

In a study of 59 patients with relapsed/refractory extranodal natural killer/T-cell lymphoma treated with pembrolizumab, the overall response rate was 40.7%, with 28.8% achieving a complete response, indicating its potential efficacy as a salvage therapy.

While pembrolizumab showed modest effectiveness, it was associated with some grade 3 or 4 adverse events in 20.3% of patients, with neutropenia being the most common, suggesting that while it can be beneficial, monitoring for side effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for Patients with Relapsed or Refractory Extranodal NK/T-Cell Lymphoma in Korea. Lee, JY., Kwon, JH., Hur, JY., 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]

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) 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]

In a phase II study involving 54 patients with aggressive B-cell lymphomas, rituximab demonstrated significant clinical activity, achieving an overall response rate of 31%, with complete responses in 9% and partial responses in 22% of patients.

The treatment was well-tolerated, with mild adverse events primarily related to infusion syndrome, indicating that rituximab could be a safe option for patients with diffuse large B-cell lymphoma (DLCL) and mantle cell lymphoma (MCL).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab (anti-CD20 monoclonal antibody) for the treatment of patients with relapsing or refractory aggressive lymphoma: a multicenter phase II study. Coiffier, B., Haioun, C., Ketterer, N., et al.[2022]

Rituximab has significantly improved outcomes for patients with Non-Hodgkin's lymphoma (NHL), particularly in aggressive forms like diffuse large B cell lymphoma (DLBCL) and follicular lymphoma (FL).

The treatment is generally well-tolerated by patients and has been shown to be cost-effective, making it a valuable option in both initial and relapsed cases of B cell NHL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab in the treatment of non-Hodgkin's lymphoma--a critical evaluation of randomized controlled trials. Griffin, MM., Morley, N.[2020]

Rituximab, an anti-CD20 monoclonal antibody, demonstrated a 43% overall response rate in a phase II trial involving 31 patients with bulky relapsed or refractory low-grade or follicular non-Hodgkin's lymphoma, indicating its efficacy as a treatment option.

The treatment was well-tolerated, with no patients discontinuing due to adverse events, and it showed a median time to progression of 8.1 months, highlighting its safety and potential for managing this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-agent monoclonal antibody efficacy in bulky non-Hodgkin's lymphoma: results of a phase II trial of rituximab. Davis, TA., White, CA., Grillo-López, AJ., et al.[2022]

In a phase I study involving 67 patients with relapsed/refractory follicular lymphoma and other CD20+ non-Hodgkin lymphomas, the combination of utomilumab and rituximab showed a favorable safety profile, with no dose-limiting toxicities and mostly mild adverse events like fatigue.

The treatment demonstrated clinical activity with an objective response rate of 21.2%, including complete and partial responses, suggesting that the effectiveness may depend on the patient's immune function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-in-Human Study of Utomilumab, a 4-1BB/CD137 Agonist, in Combination with Rituximab in Patients with Follicular and Other CD20+ Non-Hodgkin Lymphomas. Gopal, AK., Levy, R., Houot, R., et al.[2021]

In a phase II study involving 37 patients with relapsed or refractory low-grade or follicular B-cell non-Hodgkin's lymphoma, Rituximab was found to be well tolerated, with most adverse events being mild and decreasing with subsequent infusions.

The treatment resulted in a 57% overall response rate, with 14% achieving a complete response and 43% a partial response, indicating significant clinical activity and suggesting that extended Rituximab treatment may be effective for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Extended Rituximab (anti-CD20 monoclonal antibody) therapy for relapsed or refractory low-grade or follicular non-Hodgkin's lymphoma. Piro, LD., White, CA., Grillo-López, AJ., et al.[2022]

Citations

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

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

2. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of diffuse large B-cell lymphoma. [2020]

3. Korea (South) pubmed.ncbi.nlm.nih.gov

Pembrolizumab for Patients with Relapsed or Refractory Extranodal NK/T-Cell Lymphoma in Korea. [2023]

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

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

5. 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]

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

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

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

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. [2021]

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

FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. [2022]

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

Rituximab (anti-CD20 monoclonal antibody) for the treatment of patients with relapsing or refractory aggressive lymphoma: a multicenter phase II study. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Rituximab in the treatment of non-Hodgkin's lymphoma--a critical evaluation of randomized controlled trials. [2020]

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

Single-agent monoclonal antibody efficacy in bulky non-Hodgkin's lymphoma: results of a phase II trial of rituximab. [2022]

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

First-in-Human Study of Utomilumab, a 4-1BB/CD137 Agonist, in Combination with Rituximab in Patients with Follicular and Other CD20+ Non-Hodgkin Lymphomas. [2021]

13. England pubmed.ncbi.nlm.nih.gov

Extended Rituximab (anti-CD20 monoclonal antibody) therapy for relapsed or refractory low-grade or follicular non-Hodgkin's lymphoma. [2022]