Pembrolizumab + Tazemetostat for Non-Hodgkin's Lymphoma

Overseen By Study Coordinator

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Northwestern University

Must not be taking: Anti-PD-1, Anti-PD-L1

Disqualifiers: HIV, Chronic hepatitis B, 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

Compensation: Varies

Number of Visits: 1

Duration: 12 months

32 Participants Needed

Trial Summary

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

The trial protocol does not specify if you need to stop taking your current medications. However, patients receiving medications that are inhibitors or inducers of CYP450 enzymes are eligible as long as they meet the criteria. It's best to discuss your specific medications with the trial team.

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

The trial information does not specify if you need to stop taking your current medications. However, it mentions that patients receiving certain medications or substances that affect liver enzymes are eligible if they meet the criteria, suggesting some medications might be allowed. It's best to discuss your specific medications with the trial team.

What data supports the idea that Pembrolizumab + Tazemetostat for Non-Hodgkin's Lymphoma is an effective drug?

The available research does not provide specific data on the effectiveness of Pembrolizumab + Tazemetostat for Non-Hodgkin's Lymphoma. However, Pembrolizumab, one of the drugs in the combination, has been shown to be effective in treating other types of cancer, such as non-small cell lung cancer and melanoma. It works by helping the immune system attack cancer cells. There is no direct comparison or data available for its use in Non-Hodgkin's Lymphoma with Tazemetostat from the provided information. ^{1 2 3 4 5}

What data supports the effectiveness of the drug Pembrolizumab for treating Non-Hodgkin's Lymphoma?

Pembrolizumab has shown effectiveness in treating various cancers, including non-small cell lung cancer and melanoma, by targeting the PD-1 pathway, which helps the immune system attack cancer cells. While specific data for Non-Hodgkin's Lymphoma is not provided, its success in other cancers suggests potential benefits. ^{1 2 3 4 5}

What safety data is available for Pembrolizumab and Tazemetostat in treating Non-Hodgkin's Lymphoma?

The safety data for Pembrolizumab, also known as Keytruda, includes reports of immune-related adverse events (irAEs) such as pneumonitis, colitis, hepatitis, hypophysitis, hyperthyroidism, hypothyroidism, nephritis, and type 1 diabetes. These events are associated with its role as a PD-1 inhibitor used in cancer immunotherapy. While specific safety data for the combination of Pembrolizumab and Tazemetostat in Non-Hodgkin's Lymphoma is not provided in the research, Pembrolizumab has been studied in various cancers, showing a range of irAEs. Tazemetostat, known under various names, is not specifically mentioned in the provided research, so its safety profile in this combination remains to be evaluated in clinical trials. ^{1 2 4 5 6}

Is the combination of Pembrolizumab and Tazemetostat safe for humans?

Pembrolizumab, used in cancer treatment, can cause immune-related side effects like inflammation of the lungs (pneumonitis), liver (hepatitis), and thyroid issues. It has also been linked to rare cases of type 1 diabetes. While these side effects are known, specific safety data for the combination with Tazemetostat in Non-Hodgkin's Lymphoma is not provided in the available research. ^{1 2 4 5 6}

Is the drug Pembrolizumab + Tazemetostat a promising treatment for Non-Hodgkin's Lymphoma?

The information provided does not include any specific research or results about Pembrolizumab + Tazemetostat for Non-Hodgkin's Lymphoma, so we cannot determine if it is a promising treatment based on this data. ^{7 8 9 10 11}

What makes the drug Pembrolizumab + Tazemetostat unique for treating Non-Hodgkin's Lymphoma?

Pembrolizumab + Tazemetostat is unique because it combines an immune checkpoint inhibitor (Pembrolizumab) that helps the immune system attack cancer cells, with an EZH2 inhibitor (Tazemetostat) that targets a specific enzyme involved in cancer cell growth, offering a novel approach compared to traditional chemotherapy. ^{7 8 9 10 11}

What is the purpose of this trial?

This phase II trial tests how well pembrolizumab and tazemetostat work to treat patients who have received autologous stem cell transplantation (ASCT) or chimeric antigen receptor (CAR) T cell therapy for aggressive non hodgkins lymphoma. A monoclonal antibody, such as pembrolizumab, is a type of protein that can bind to certain targets in the body, such as molecules that cause the body to make an immune response (antigens). Tazemetostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving pembrolizumab and tazemetostat may work better to treat patients who have received ASCT or CAR-T cell therapy for aggressive non hodgkins lymphoma.

Research Team

Reem Karmali

Principal Investigator

Northwestern University

Eligibility Criteria

This trial is for patients with aggressive B-cell Non-Hodgkin's Lymphoma who have already undergone autologous stem cell transplantation (ASCT) or chimeric antigen receptor (CAR) T-cell therapy. Specific eligibility criteria are not provided, but typically include factors like age, health status, and previous treatments.

Inclusion Criteria

FOCBP must practice complete abstinence or agree to use two reliable methods of contraception simultaneously

My platelet count is at least 50,000 and was checked within the last 14 days.

My blood clotting time is near normal.

Exclusion Criteria

Patients who are currently participating in or has participated in a study of an investigational agent within 28 days prior to the first dose of study intervention

I have an autoimmune disease treated with medication in the last 2 years.

Patients with an uncontrolled intercurrent illness

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive pembrolizumab IV on day 1 of each cycle and tazemetostat PO BID starting cycle 2, with cycles repeating every 21 days for 12 months

12 months

Monthly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

18 months

Periodic visits (in-person)

Treatment Details

Interventions

• Pembrolizumab
• Tazemetostat

Trial Overview The trial is testing the combination of pembrolizumab (a monoclonal antibody that helps the immune system detect and fight cancer cells) and tazemetostat (a drug that may stop cancer growth by blocking certain enzymes), to see if they can improve outcomes in patients post-ASCT or CAR-T therapy.

Participant Groups

Group I: Treatment (pembrolizumab, tazemetostat) Experimental Treatment 6 Interventions

Starting on day 14 after standard of care ASCT or CAR-T cell treatment patients receive pembrolizumab IV on day 1 of each cycle. Starting cycle 2, patients receive tazemetostat PO BID on days 1-21 of each cycle. Cycles repeat every 21 days for 12 months in the absence of disease progression or unacceptable toxicity. Patients undergo echocardiography during screening, CT scan, PET scan, and blood sample collection throughout the study.

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?

Northwestern University

Lead Sponsor

Trials

1,674

Recruited

989,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

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]

Pembrolizumab (Keytruda) is approved for treating advanced endometrial carcinoma that is microsatellite instability-high or mismatch repair deficient, specifically for patients whose disease has progressed after previous treatments.

This approval is significant for patients who are not candidates for curative surgery or radiation, providing a new therapeutic option for a challenging stage of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Approved Use for Keytruda. Aschenbrenner, DS.[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, 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]

An elderly male patient on pembrolizumab developed four autoimmune toxicities, including type 1 diabetes and pneumonitis, highlighting the risk of multiple immune-related adverse events associated with this treatment.

The case suggests that aging may increase susceptibility to these adverse effects, necessitating close monitoring and prompt management, including stopping the immunotherapy and using steroids for treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multiple autoimmune side effects of immune checkpoint inhibitors in a patient with metastatic melanoma receiving pembrolizumab. Kethireddy, N., Thomas, S., Bindal, P., et al.[2021]

Certolizumab pegol (CZP) combined with methotrexate (MTX) significantly improved the ACR20 response rate in patients with active rheumatoid arthritis compared to placebo + MTX, with higher efficacy observed at the 400 mg dosage.

The safety profile of CZP + MTX was comparable to that of MTX alone, as there were no significant differences in the number of adverse event-related withdrawals among the treatment groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of methotrexate plus certolizumab pegol or placebo in active rheumatoid arthritis : Meta-analysis of randomized controlled trials. Lee, YH., Bae, SC.[2019]

Certolizumab pegol (Cimzia) is the only PEGylated anti-TNFα biologic approved for treating rheumatoid arthritis and Crohn's disease, highlighting its unique position in the market since its approval in 2009 for rheumatoid arthritis and earlier for Crohn's disease.

Clinical data show that certolizumab pegol provides significant benefits in various outcomes, including clinical, radiographic, and patient-reported measures, making it a valuable treatment option in a competitive landscape.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Certolizumab pegol. Goel, N., Stephens, S.[2022]

Certolizumab pegol (CZP) demonstrated sustained efficacy in treating moderate-to-severe plaque psoriasis over three years, with 70.6% of patients achieving at least a 75% improvement in psoriasis severity (PASI 75) at week 144 for the 200 mg dose, and 72.9% for the 400 mg dose.

The higher dose of CZP (400 mg) showed numerically better outcomes compared to the lower dose, indicating that dose adjustments based on patient response can enhance treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term efficacy of certolizumab pegol for the treatment of plaque psoriasis: 3-year results from two randomized phase III trials (CIMPASI-1 and CIMPASI-2). Gordon, KB., Warren, RB., Gottlieb, AB., et al.[2021]

Tezepelumab, a monoclonal antibody targeting thymic stromal lymphopoietin, is being evaluated for its long-term safety and efficacy in patients with severe, uncontrolled asthma in the DESTINATION study, which includes participants from two previous phase 3 trials.

The study aims to assess not only the long-term tolerability and effect on asthma exacerbations over 104 weeks but also the clinical benefits after treatment cessation, providing insights into its potential as a corticosteroid-sparing therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

DESTINATION: a phase 3, multicentre, randomized, double-blind, placebo-controlled, parallel-group trial to evaluate the long-term safety and tolerability of tezepelumab in adults and adolescents with severe, uncontrolled asthma. Menzies-Gow, A., Ponnarambil, S., Downie, J., et al.[2021]

Certolizumab pegol (Cimzia®) is an effective treatment for various inflammatory autoimmune diseases, including Crohn's disease, rheumatoid arthritis, psoriatic arthritis, and axial spondyloarthritis, as demonstrated in well-designed clinical trials.

The drug is generally well tolerated, with common side effects including upper respiratory tract infections, rash, and urinary tract infections, making it a safe option for managing these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Certolizumab Pegol: A Review in Inflammatory Autoimmune Diseases. Deeks, ED.[2017]

References

1. 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]

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

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

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

New Approved Use for Keytruda. [2022]

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

Pembrolizumab: first global approval. [2021]

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

Multiple autoimmune side effects of immune checkpoint inhibitors in a patient with metastatic melanoma receiving pembrolizumab. [2021]

7. Germany pubmed.ncbi.nlm.nih.gov

Efficacy and safety of methotrexate plus certolizumab pegol or placebo in active rheumatoid arthritis : Meta-analysis of randomized controlled trials. [2019]

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

Certolizumab pegol. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Long-term efficacy of certolizumab pegol for the treatment of plaque psoriasis: 3-year results from two randomized phase III trials (CIMPASI-1 and CIMPASI-2). [2021]

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

DESTINATION: a phase 3, multicentre, randomized, double-blind, placebo-controlled, parallel-group trial to evaluate the long-term safety and tolerability of tezepelumab in adults and adolescents with severe, uncontrolled asthma. [2021]

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

Certolizumab Pegol: A Review in Inflammatory Autoimmune Diseases. [2017]