Pembrolizumab + Vorinostat for Lymphoma

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: City of Hope Medical Center

Must not be taking: Steroids, Immunosuppressants, Valproic acid

Disqualifiers: Immunodeficiency, Active TB, Autoimmune, others

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

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

Compensation: Varies

Number of Visits: Unknown

Duration: 24 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two drugs, pembrolizumab (an immunotherapy drug) and vorinostat (a histone deacetylase inhibitor), to treat certain types of lymphoma that have returned or didn't respond to previous treatments. Pembrolizumab helps the immune system fight cancer, while vorinostat stops cancer cells from growing. Researchers aim to determine if using both drugs together is more effective than using pembrolizumab alone. Individuals with diffuse large B-cell lymphoma, follicular lymphoma, or Hodgkin lymphoma that has relapsed or is treatment-resistant might be suitable for this study. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this combination therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot participate if you are on certain treatments like systemic steroids or other immunosuppressive therapies within 7 days before starting the trial, or if you've taken valproic acid or similar drugs within 2 weeks before the trial.

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

Research has shown that the combination of pembrolizumab and vorinostat is generally safe for people. In earlier studies, patients with B-cell non-Hodgkin lymphoma (NHL) who received this treatment found it manageable and effective, with serious side effects being rare. Another study found that this combination also helped patients with Hodgkin lymphoma who did not respond to other treatments.

This trial is in the early stages, primarily aiming to find a safe dose and identify any side effects. However, since pembrolizumab and vorinostat have been studied together before with positive results, the treatment appears promising in terms of safety. Individual experiences can differ, so discussing any concerns with a healthcare provider is always advisable. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of pembrolizumab and vorinostat for treating lymphoma because it brings a fresh approach to tackling the disease. Pembrolizumab is an immune checkpoint inhibitor that helps the body's immune system recognize and attack cancer cells, a mechanism different from traditional chemotherapy. Vorinostat, on the other hand, is a histone deacetylase inhibitor that can potentially make cancer cells more susceptible to immune attack and other treatments. Together, these drugs offer a promising new way to enhance the immune response against lymphoma, potentially leading to better outcomes for patients who may not respond well to existing therapies like chemotherapy and radiation.

What evidence suggests that pembrolizumab and vorinostat might be an effective treatment for lymphoma?

This trial will evaluate the combination of pembrolizumab and vorinostat for lymphoma. Research has shown that this combination can be effective for some types of lymphoma. Specifically, in patients with B-cell non-Hodgkin lymphoma that has returned or is difficult to treat, this combination has produced positive results. Notably, even patients with Hodgkin lymphoma who did not respond to previous treatments with PD-1 blockers have benefited from this approach. Pembrolizumab, a type of immunotherapy, helps the body's immune system fight cancer, while vorinostat inhibits cancer cell growth. Together, they appear to enhance each other's effects, offering hope for these challenging cancers. ^{1 2 3 4 6}

Who Is on the Research Team?

Alex F Herrera

Principal Investigator

City of Hope Medical Center

Are You a Good Fit for This Trial?

This trial is for patients with certain types of lymphoma (diffuse large B-cell, follicular, or Hodgkin) that have returned or resisted treatment. Participants must have measurable disease, adequate organ function, and not be candidates for a stem cell transplant. They should agree to use contraception and can't join if they're pregnant/breastfeeding, have had recent immunotherapy or live vaccines, suffer from severe infections like TB/HIV/hepatitis B/C, or are on immunosuppressants.

Inclusion Criteria

My cancer returned or didn't fully respond after at least one treatment.

Platelets >= 75,000/mcL (within 14 days of treatment initiation)

I am willing to use birth control during and for 4 months after the study.

Exclusion Criteria

I have not used any experimental drugs or devices in the last 3 weeks.

I haven't had cancer treatment with monoclonal antibodies in the last 3 weeks or have recovered from their side effects.

You have a severe allergy to pembrolizumab or any of its ingredients.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive vorinostat orally twice daily on days 1-5 and 8-12 and pembrolizumab intravenously on day 1. Cycles repeat every 21 days for up to 24 months.

24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-up at 30 days and then every 12 weeks.

up to 27 months

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab
• Vorinostat

Trial Overview The trial tests the combination of Pembrolizumab (an immune system-boosting drug) with Vorinostat (a drug that blocks enzymes needed by cancer cells to grow). It aims to find the safest dose and see if this combo is more effective than Pembrolizumab alone in treating relapsed/refractory lymphomas.

How Is the Trial Designed?

Group I: Vorinostat 200mg + Pembrolizumab 200mg Experimental Treatment 3 Interventions

Patients receive Vorinostat 200mg PO BID on days 1-5 and 8-12 and pembrolizumab 200mg IV over 30 minutes on day 1. Cycles repeat every 21 days for 24 months in the absence of disease progression or unacceptable toxicity.

Group II: Vorinostat 100mg + Pembrolizumab 200mg Experimental Treatment 3 Interventions

Patients receive Vorinostat 100mg PO BID on days 1-5 and 8-12 and pembrolizumab 200mg IV over 30 minutes on day 1. Cycles repeat every 21 days for 24 months in the absence of disease progression or unacceptable toxicity.

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?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Vorinostat (SAHA) shows varying effectiveness in treating breast cancer, with some tumors and cell lines being resistant due to differences in gene expression related to cell adhesion and glutathione metabolism.

Depleting glutathione with buthionine sulfoximine (BSO) can enhance the effectiveness of SAHA, suggesting that evaluating antioxidant gene expression may help predict which tumors will respond to this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Redox-Mediated Suberoylanilide Hydroxamic Acid Sensitivity in Breast Cancer. Chiaradonna, F., Barozzi, I., Miccolo, C., et al.[2018]

In a phase 1 study involving 32 patients with relapsed/refractory classical Hodgkin lymphoma, the combination of vorinostat and pembrolizumab showed a high overall response rate (ORR) of 72%, indicating effective treatment for this challenging condition.

The treatment was well tolerated, with manageable adverse events, and demonstrated efficacy even in patients who were previously refractory to anti-PD-1 therapy, achieving an ORR of 56% in this subgroup.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus vorinostat induces responses in patients with Hodgkin lymphoma refractory to prior PD-1 blockade. Mei, M., Chen, L., Godfrey, J., et al.[2023]

The combination of pembrolizumab and vorinostat was found to be tolerable in patients with relapsed/refractory B-cell lymphomas, although there were serious adverse events, including one case of Stevens-Johnson syndrome that led to a fatal infection.

The treatment showed promising efficacy, especially in primary mediastinal B-cell lymphoma (PMBL), with a complete response rate of 80% and overall response rate of 80%, while overall response rates for other non-PMBL diffuse large B-cell lymphoma (DLBCL) were lower at 33%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Results from a phase I trial of pembrolizumab plus vorinostat in relapsed/refractory B-cell non-Hodgkin lymphoma. Godfrey, J., Mei, M., Chen, L., et al.[2023]

In a phase I study involving 23 advanced-stage cancer patients, vorinostat was found to be safe and tolerable, with common side effects including mild to moderate nausea and fatigue.

The study revealed that a high-fat meal slightly increased the absorption of vorinostat but did not significantly impact its overall effectiveness, suggesting that vorinostat can be administered with or without food in future studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A study to determine the effects of food and multiple dosing on the pharmacokinetics of vorinostat given orally to patients with advanced cancer. Rubin, EH., Agrawal, NG., Friedman, EJ., et al.[2018]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37470137/

Results from a phase I trial of pembrolizumab plus vorinostat ... Pembrolizumab with vorinostat was tolerable and produced responses in relapsed/refractory B-cell NHL, with particularly notable efficacy in PMBL.

2. ashpublications.org ashpublications.org/blood/article/142/16/1359/496475/Pembrolizumab-plus-vorinostat-induces-responses-in

Pembrolizumab plus vorinostat induces responses in patients ... Pembrolizumab plus vorinostat induces responses in patients with Hodgkin lymphoma refractory to prior PD-1 blockade.

3. nature.com nature.com/articles/s43018-025-01004-2

Efficacy of pembrolizumab and vorinostat combination in ... Here, we present the efficacy and safety results of the phase 2 PEVOsq basket trial investigating the combination of the ICI inhibitor ...

4. haematologica.org haematologica.org/article/view/11170

Results from a phase I trial of pembrolizumab plus ... In conclusion, pembrolizumab with vorinostat was tolerable and produced responses in relapsed/refractory B-cell NHL, with particularly notable ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10828763/

Results from a phase I trial of pembrolizumab plus ... Pembrolizumab with vorinostat was tolerable and produced responses in relapsed/refractory B-cell NHL, with particularly notable efficacy in PMBL.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05008224

NCT05008224 | Study of Safety and Efficacy ... The purpose of this study is to evaluate the safety and efficacy of pembrolizumab (MK-3475) monotherapy, followed by chemotherapy, followed by pembrolizumab ...