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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of combining pembrolizumab and tazemetostat in treating aggressive non-Hodgkin's lymphoma after patients have received stem cell or CAR-T cell therapy. Pembrolizumab is a protein that aids the immune system in targeting cancer, while tazemetostat may inhibit cancer cell growth by blocking certain essential enzymes. Participants should have undergone stem cell or CAR-T cell therapy for aggressive B-cell non-Hodgkin's lymphoma and may still have active disease before joining the trial. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

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.

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

Research has shown that using pembrolizumab with tazemetostat is generally safe for patients. In one study, 33% of patients experienced moderate side effects, but no serious problems or deaths were linked to the treatment. Another study found that taking 800 mg of tazemetostat with pembrolizumab was well-tolerated. Common side effects included manageable low red blood cell counts. Compared to similar drugs, tazemetostat posed a lower risk of safety issues while maintaining effectiveness. Overall, the combination of pembrolizumab and tazemetostat is considered safe and practical for patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about pembrolizumab and tazemetostat for treating Non-Hodgkin's Lymphoma because they bring a fresh angle to cancer therapy. Unlike standard treatments that often rely on broad-spectrum chemotherapy, pembrolizumab is an immune checkpoint inhibitor that helps the immune system recognize and attack cancer cells more effectively. Tazemetostat, on the other hand, is an EZH2 inhibitor that targets specific genetic mutations in cancer cells, potentially halting their growth. Together, these drugs aim to provide a more targeted and potentially less toxic treatment option for patients.

What evidence suggests that pembrolizumab and tazemetostat might be effective for non-Hodgkin's lymphoma?

This trial will evaluate the combination of pembrolizumab and tazemetostat for non-Hodgkin's lymphoma. Studies have shown that using pembrolizumab and tazemetostat together can help control tumors. Pembrolizumab aids the immune system in identifying and destroying cancer cells, while tazemetostat inhibits certain enzymes essential for cancer cell growth. Research suggests that tazemetostat has led to lasting tumor responses in B-cell non-Hodgkin's lymphoma. In lab studies, this combination has shown promise in controlling tumors. However, specific data on its effectiveness for non-Hodgkin's lymphoma is not yet available. ^{1 3 6 7 8}

Who Is on the Research Team?

Reem Karmali

Principal Investigator

Northwestern University

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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, 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]

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]

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 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]

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]

Citations

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Tazemetostat, a Selective EZH2 Inhibitor, in Combination with ... Laboratory studies have shown that tumor control is improved with the addition of tazemetostat to pembrolizumab. This drug combination has not ...

2. withpower.com withpower.com/trial/phase-2-lymphoma-b-cell-non-hodgkins-lymphoma-3-2024-8dc42

Pembrolizumab + Tazemetostat for Non-Hodgkin's Lymphoma The available research does not provide specific data on the effectiveness of Pembrolizumab + Tazemetostat for Non-Hodgkin's Lymphoma. However, Pembrolizumab ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05023655?term=tazemetostat&viewType=Table&rank=6

Phase II Study of Tazemetostat in Solid Tumors Harboring ... Tazemetostat has been shown to produce durable tumor responses in patients with B-cell non-Hodgkin's lymphoma and epithelioid sarcomas. Responses have also ...

4. clin.larvol.com clin.larvol.com/trial-detail/NCT06242834

Pembrolizumab and Tazemetostat to Overcome Immune ... Overall survival, Will be estimated using the method of Kaplan-Meier. From ASCT or CAR T-cell infusion until death from any cause, up to 3 years ; Incidence of ...

5. aacrjournals.org aacrjournals.org/mct/article/13/4/842/91698/Selective-Inhibition-of-EZH2-by-EPZ-6438-Leads-to

Selective Inhibition of EZH2 by EPZ-6438 Leads to Potent ... Selective inhibition of EZH2 by EPZ-6438 leads to potent antitumor activity in EZH2-mutant non-Hodgkin lymphoma.

6. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2024-00285

Pembrolizumab and Tazemetostat to Overcome Immune ... Giving pembrolizumab and tazemetostat may work better to treat patients who have received ASCT or CAR-T cell therapy for aggressive non hodgkins lymphoma.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8989805/

Tazemetostat was Associated with a Lower Risk for Safety ... Tazemetostat was associated with lower RR for safety outcomes versus idelalisib, duvelisib, copanlisib, and umbralisib, while achieving similar efficacy ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT01897571

NCT01897571 | Study of Tazemetostat as Single Agent in ... This is an open-label, multicenter, Phase 1/2 study of tazemetostat as a single agent in subjects with advanced solid tumors or with B-cell lymphomas.