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

52 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This phase I trial studies the side effects and best dose of vorinostat when given together with pembrolizumab in treating patients with diffuse large B-cell lymphoma, follicular lymphoma, or Hodgkin lymphoma that has come back after a period of improvement or that does not respond to treatment. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer and may interfere with the ability of cancer cells to grow and spread. Vorinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving vorinostat and pembrolizumab together may work better than pembrolizumab alone in treating patients with diffuse large B-cell lymphoma, follicular lymphoma, or Hodgkin lymphoma.

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.

What makes the drug combination of Pembrolizumab and Vorinostat unique for treating lymphoma?

The combination of Pembrolizumab and Vorinostat is unique because it combines an immune checkpoint inhibitor (Pembrolizumab) with a histone deacetylase inhibitor (Vorinostat), which together enhance the immune system's ability to fight cancer cells, especially in patients who are resistant to previous PD-1 blockade therapies. This combination has shown promising response rates in relapsed or refractory Hodgkin lymphoma, including in patients who did not respond to prior PD-1 therapies. ^{1 2 3 4 5}

What data supports the effectiveness of the drug Pembrolizumab + Vorinostat for lymphoma?

A phase I trial showed that Pembrolizumab combined with Vorinostat was tolerable and produced responses in relapsed/refractory B-cell non-Hodgkin lymphoma, with particularly notable effectiveness in primary mediastinal B-cell lymphoma (PMBL), where 80% of patients had a complete response. ^{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

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]

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 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]

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]

Citations

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

Vorinostat in Combination With Lenalidomide and Dexamethasone in Lenalidomide-Refractory Multiple Myeloma. [2018]

2. Italy pubmed.ncbi.nlm.nih.gov

Results from a phase I trial of pembrolizumab plus vorinostat in relapsed/refractory B-cell non-Hodgkin lymphoma. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Aminosuberoyl hydroxamic acids (ASHAs): a potent new class of HDAC inhibitors. [2009]

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

Redox-Mediated Suberoylanilide Hydroxamic Acid Sensitivity in Breast Cancer. [2018]

5. United States 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. [2018]

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

Pembrolizumab plus vorinostat induces responses in patients with Hodgkin lymphoma refractory to prior PD-1 blockade. [2023]