Pembrolizumab for T-Cell Lymphoma

Not currently recruiting at 18 trial locations

Overseen By Joachim Yahalom, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Corticosteroids, Immunosuppressive drugs

Disqualifiers: Prior treatment, Active infection, 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: Unknown

Duration: 8-12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests how well pembrolizumab, a type of medication, can shrink T-cell lymphoma tumors in patients who haven't undergone chemotherapy. It focuses on Early-Stage NK/T-cell Lymphoma (ENKTL), a condition affecting the immune system. People with ENKTL who have not received prior treatment might be suitable for this trial. The goal is to determine if pembrolizumab can effectively reduce tumor size and improve patient outcomes. As a Phase 2 trial, the research measures the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

Is there any evidence suggesting that pembrolizumab is likely to be safe for humans?

Research shows that pembrolizumab is generally well-tolerated by people with NK/T-cell lymphoma. Studies have found it safe and effective for those with relapsed or hard-to-treat stages of the disease. In these studies, many patients experienced long-lasting improvement in their cancer symptoms.

Previous research indicates that pembrolizumab is usually safe when combined with chemotherapy, with no unexpected serious side effects reported. This supports its safety. However, like any treatment, some side effects may occur. Participants should discuss any concerns with their doctor before joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for lymphoma?

Pembrolizumab is unique because it leverages the power of the immune system to fight T-cell lymphoma, a type of cancer affecting the immune cells. Unlike traditional chemotherapy, which targets rapidly dividing cells, pembrolizumab is an immune checkpoint inhibitor. It works by blocking the PD-1 pathway, which cancer cells often exploit to hide from the immune system. By doing this, pembrolizumab helps unleash the body's natural defenses to recognize and attack cancer cells more effectively. Researchers are excited about pembrolizumab because it offers a more targeted approach, potentially leading to better outcomes with fewer side effects compared to conventional treatments.

What evidence suggests that pembrolizumab might be an effective treatment for NK/T-cell Lymphoma?

Research has shown that pembrolizumab effectively treats extranodal NK/T-cell lymphoma, particularly in patients whose cancer has returned or didn't respond to other treatments. Past studies demonstrated that pembrolizumab significantly reduced tumor size in many patients with this lymphoma type. The drug blocks a protein called PD-1, enabling the immune system to find and attack cancer cells more effectively. In this trial, researchers are testing pembrolizumab in two separate treatment arms for early-stage NK/T-cell lymphoma: one for Stage I/II and another for Stage III/IV. The positive results in patients with relapsed cancer suggest that pembrolizumab might also benefit early-stage patients who haven't yet undergone chemotherapy. Overall, pembrolizumab has shown strong potential to improve treatment outcomes for this condition. ^{1 6 7 8 9}

Who Is on the Research Team?

Alison Moskowitz, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

Adults with early-stage NK/T-cell lymphoma, nasal type, who haven't had chemotherapy can join this trial. They must be generally healthy with good organ function and performance status. Women of childbearing age need a negative pregnancy test and agree to use contraception; men also have to agree to effective birth control or abstinence.

Inclusion Criteria

I can carry out all my self-care but cannot do heavy physical work.

I am not pregnant, will use birth control, and won't have unprotected sex during the study.

My kidney, liver, heart, and lung functions meet the required levels.

Exclusion Criteria

I have had pneumonitis treated with steroids or have it now.

Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial

I have been diagnosed with HIV.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pembrolizumab to test its effectiveness in shrinking Early-Stage NK/T-cell Lymphoma

8-12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab

Trial Overview The study is testing pembrolizumab's effectiveness in shrinking early-stage NK/T-cell lymphoma before any chemotherapy is given. Participants will receive pembrolizumab and their response to the treatment will be monitored.

How Is the Trial Designed?

Group I: Early-Stage NK/T-cell Lymphoma/ENKTL (Stage III/IV) Experimental Treatment 1 Intervention

Group II: Early-Stage NK/T-cell Lymphoma/ENKTL (Stage I/II) Experimental Treatment 1 Intervention

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?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Published Research Related to This Trial

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]

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 anti-PD-1 therapy, shows a high objective response rate of 84.5% in patients with refractory or recurrent NK/T-cell lymphoma, indicating its efficacy as a treatment option.

The treatment resulted in a complete response rate of 61.6% and demonstrated good disease-free survival ranging from 2 to 48 months, with low adverse events reported, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of PD-1 blockade in refractory/relapsed natural killer T-cell lymphomas: a systematic review and synthesis of case reports. Rivera-Francia, VM., Failoc-Rojas, VE., Villacorta-Carranza, R., 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]

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]

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) 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, 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. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/3068/532750/Pembrolizumab-for-Front-Line-Treatment-of

Pembrolizumab for Front-Line Treatment of Extranodal NK/T ... Introduction: Pembrolizumab is highly active in relapse or refractory extranodal NK/T-cell lymphoma (ENKTL) and therefore has potential to ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497124058208

Pembrolizumab for Front-Line Treatment of Extranodal NK ... Pembrolizumab is highly active in relapse or refractory extranodal NK/T-cell lymphoma (ENKTL) and therefore has potential to improve efficacy and tolerability ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37946408/

Pembrolizumab for Patients with Relapsed or Refractory ... Programmed death-1 blockade with pembrolizumab has shown promising activity in relapsed/refractory (R/R) extranodal natural killer/T-cell lymphoma (NKTCL), but ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03728972

Study of Pembrolizumab in Patients With Early-Stage NK/T- ... The purpose of this study is to test how well pembrolizumab shrinks Early-Stage NK/T-cell Lymphoma (ENKTL) in participants who have not yet received ...

5. e-crt.org e-crt.org/journal/view.php?number=3553

Pembrolizumab for Patients with Relapsed or Refractory ... Programmed death-1 blockade with pembrolizumab has shown promising activity in relapsed/refractory (R/R) extranodal natural killer/T-cell lymphoma (NKTCL), but ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S0006497123083295

Pembrolizumab in Relapsed/Refractory Extranodal NK/T ... Pembrolizumab is a safe and efficacious therapy for R/R ENKTL with potentially durable remission. In R/R mature T-cell lymphomas, the benefit of pembrolizumab ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5793390/

Activity of pembrolizumab in relapsed/refractory NK/T-cell ... Current data indicate that advanced-stage and relapsed/refractory NK/T-cell lymphoma should be treated with L-asparaginase-containing regimens ...

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

keytruda_pi.pdf Safety data are available for the first 203 patients who received KEYTRUDA and chemotherapy (n=101) or placebo and chemotherapy (n=102). Patients with ...

9. e-crt.org e-crt.org/upload/pdf/crt-2023-1042.pdf

Pembrolizumab for Patients with Relapsed or Refractory ... The majority of patients (22/26, 84.6%) were treated for pembrolizumab- refractory disease and the remaining patients (4/26, 15.4%) were treated ...