Pembrolizumab + Romidepsin for Lymphoma

Overseen By Swaminathan P. Iyer, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Strong CYP3A4 inhibitors

Disqualifiers: Active TB, CNS metastases, 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: Up to 36 cycles (approximately 2 years)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effects of combining pembrolizumab, an immunotherapy drug that helps the immune system attack cancer, with romidepsin, which may stop cancer cell growth, to treat peripheral T-cell lymphoma that has returned or isn't responding to treatment. Researchers aim to understand the side effects and effectiveness of this combination therapy. It targets individuals with peripheral T-cell lymphoma who have tried at least one other treatment and have a measurable tumor. 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 novel combination therapy.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot participate if you are currently receiving another study therapy or have used an investigational agent within 4 weeks of starting this trial. Also, you should not use strong CYP3A4 inhibitors and inducers while participating in 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 romidepsin is generally well-tolerated. Studies have found this combination to be safe. Early results are promising for treating peripheral T-cell lymphoma that returns or doesn't respond to other treatments. While all treatments can have side effects, data so far suggest that most people manage these drugs without major problems. Participants in the clinical trial will have their health closely monitored to address any concerns promptly. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of pembrolizumab and romidepsin for treating lymphoma because it offers a unique approach compared to traditional therapies. Pembrolizumab is an immunotherapy, which works by blocking a protein called PD-1 on the surface of immune cells, unleashing the immune system to attack cancer cells more effectively. When combined with romidepsin, a histone deacetylase inhibitor that alters the expression of certain genes to induce cancer cell death, this duo offers a powerful one-two punch that enhances the immune response while directly targeting cancer cell survival mechanisms. This combination has the potential to improve outcomes for patients who might not respond well to standard chemotherapy regimens.

What evidence suggests that pembrolizumab and romidepsin might be an effective treatment for peripheral T-cell lymphoma?

Research has shown that combining pembrolizumab and romidepsin may help treat peripheral T-cell lymphoma, especially when other treatments have failed. In earlier studies, this combination benefited 50% of patients with relapsed or hard-to-treat T-cell lymphoma. In this trial, participants will receive both pembrolizumab, an immunotherapy that helps the immune system target cancer cells, and romidepsin, which inhibits enzymes necessary for cancer cell growth. Together, these treatments might outperform pembrolizumab alone. Early results are promising, indicating potential disease control in challenging cases. ^{2 5 6 7 8}

Who Is on the Research Team?

Swaminathan P. Iyer

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for people with peripheral T-cell lymphoma that's come back or didn't respond to treatment. They must have had at least one prior treatment, be in good physical condition (ECOG 0 or 1), and have adequate organ function. Pregnant women can't participate, and participants must agree to use contraception.

Inclusion Criteria

Patients irrespective of transplant eligibility status can be enrolled; however, patients can be seen by SCT team in anticipation for SCT

My PTCL is visible on scans and is larger than 1.5cm.

I agree to provide a recent biopsy sample of my tumor.

Exclusion Criteria

I am currently on medication for an infection.

I have not received a live vaccine in the last 30 days.

I have had or currently have lung inflammation treated with steroids.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive romidepsin IV over 4 hours on days 1 and 8 or day 8 of cycle 1 and days 1 and 8 of subsequent cycles and pembrolizumab IV over 30 minutes on day 1. Cycles repeat every 21 days for up to 36 cycles.

Up to 36 cycles (approximately 2 years)

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 3 years

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab
• Romidepsin

Trial Overview The study tests pembrolizumab combined with romidepsin against recurrent or refractory peripheral T-cell lymphoma. Pembrolizumab boosts the immune system to fight cancer, while romidepsin blocks enzymes needed for tumor cell growth.

How Is the Trial Designed?

Group I: Treatment (romidepsin, pembrolizumab) Experimental Treatment 2 Interventions

Participants receive romidepsin IV over 4 hours on days 1 and 8 or day 8 of cycle 1 and days 1 and 8 of subsequent cycles and pembrolizumab IV over 30 minutes on day 1. Cycles repeat every 21 days for up to 36 cycles 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?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

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]

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, 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]

Nivolumab and pembrolizumab are FDA-approved monoclonal antibodies that target PD-1, helping to enhance T cell activity against cancer by blocking the PD-1/PD-L1 interaction, which allows cancer cells to escape immune detection.

Both drugs have shown efficacy across multiple cancer types, including melanoma and non-small cell lung cancer, and are considered interchangeable options for treating these conditions, which may help manage the rising costs of cancer therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab and pembrolizumab: Monoclonal antibodies against programmed cell death-1 (PD-1) that are interchangeable. Prasad, V., Kaestner, V.[2022]

Pembrolizumab, an immune checkpoint inhibitor, can cause pneumonitis in 1%-5% of patients, and this case report highlights an atypical presentation of this side effect in a patient with metastatic squamous cell carcinoma.

The patient was successfully treated with steroid therapy after ruling out other potential causes, leading to complete resolution of the pneumonitis, emphasizing the importance of recognizing and managing atypical cases of checkpoint inhibitor-pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. Jeon, WJ., Nguyen, J., Castillo, DR., et al.[2023]

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]

In patients with relapsed and refractory classical Hodgkin's lymphoma who have previously failed treatment with brentuximab vedotin, pembrolizumab significantly improves progression-free survival (PFS) compared to standard of care, with hazard ratios indicating a much lower risk of disease progression.

The study involved a systematic literature review and comparisons of outcomes from pembrolizumab's KEYNOTE-087 trial against an observational study of standard care, confirming that pembrolizumab is a more effective treatment option for this challenging patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab versus the standard of care for relapsed and refractory classical Hodgkin's lymphoma progressing after brentuximab vedotin: an indirect treatment comparison. Keeping, S., Wu, E., Chan, K., et al.[2019]

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]

Citations

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A Phase I/II Study to Examine the Safety and Efficacy of ... ... Pembrolizumab has demonstrated acceptable safety and early encouraging results ... lymphoma, t-cell, peripheral, pembrolizumab, romidepsin, ...

2. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2018-01051

Pembrolizumab and Romidepsin in Treating Participants ... This phase I/II trial studies the side effects of pembrolizumab and romidepsin and to see how well they work in treating participants with peripheral T-cell ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7433797/

Phase II Study of the PD1-inhibitor Pembrolizumab for the ... The median time to best response was 114 days (range 82–146). Figure 2D shows the changes of tumor volume at time of best response. Fig. 2. Treatment outcomes.

4. withpower.com withpower.com/trial/pembrolizumab-romidepsin-for-lymphoma-64635

Pembrolizumab + Romidepsin for Lymphoma 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%, ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S0006497118698428

A Phase II Study of Pembrolizumab in Combination with ... CONCLUSIONS: The combination of Romidepsin and Pembrolizumab in patients with r/r TCL demonstrates an ORR of 50% which was durable and with ...

6. mdanderson.org mdanderson.org/patients-family/diagnosis-treatment/clinical-trials/clinical-trials-index/clinical-trials-detail.ID2017-0272.html

A Phase I/II Study of Pembrolizumab (MK-3475) in ... Giving pembrolizumab and romidepsin may work better than pembrolizumab alone in treating participants with recurrent or refractory peripheral T-cell lymphoma.

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2152265023013927

Abstracts T-Cell Lymphoma TCL-275 Updated Results of ... romidepsin and pembrolizumab lead to high response rates and prolonged remissions. The combination has promising PFS and OS in r/r TFH subtype of TCL.

8. clinicaltrials.gov clinicaltrials.gov/study/NCT03278782

NCT03278782 | Study of Pembrolizumab (MK-3475) in ... Evaluate the safety of pembrolizumab in combination with romidepsin. Estimate the response rate of the combination therapy in refractory or recurrent PTCL.