Pembrolizumab for Lymphoma

Overseen By Snehal Somalwar

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Abramson Cancer Center of the University of Pennsylvania

Must be taking: Pembrolizumab

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

Disqualifiers: Pregnancy, Autoimmune disease, Active infection, 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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 5 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of pembrolizumab, an immune therapy drug, and low-dose radiation to evaluate its effectiveness for individuals with non-Hodgkin lymphoma, a type of blood cancer. The goal is to determine if this treatment can help when other treatments have failed. It suits those with relapsed or refractory lymphoma, meaning their disease has returned or not responded after at least two previous treatments and they have at least two measurable cancer areas. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

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, you cannot have received certain cancer therapies or live vaccines shortly before starting the trial.

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

Research has shown that pembrolizumab is generally well-tolerated. In one study, 61% of patients experienced drug-related side effects, but most were mild. Importantly, no patients discontinued treatment due to these side effects. Another study found that pembrolizumab, when used in individuals with relapsed or hard-to-treat Hodgkin lymphoma, had a manageable safety profile. This indicates that while some side effects may occur, they are usually not severe enough to warrant stopping treatment. Overall, pembrolizumab has demonstrated safety for individuals in these situations. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for lymphoma?

Pembrolizumab is unique because it harnesses the power of the immune system to fight lymphoma. Unlike traditional chemotherapy or radiation, which directly attack cancer cells, pembrolizumab is an immune checkpoint inhibitor. It works by blocking a protein called PD-1 on immune cells, allowing them to better recognize and destroy cancer cells. Researchers are excited because combining pembrolizumab with low-dose radiation therapy might enhance its effectiveness, potentially offering a more targeted and less toxic treatment option for lymphoma patients.

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

Research has shown that pembrolizumab, a type of immunotherapy, yields promising results in treating various lymphomas, including non-Hodgkin lymphoma. Studies have found that it helps shrink tumors. Specifically, in the KEYNOTE-087 trial, pembrolizumab demonstrated a strong overall response rate, effectively reducing signs of cancer. Additionally, long-term data suggests that pembrolizumab can extend patient survival by lowering the risk of death. In this trial, participants will receive pembrolizumab combined with low-dose radiation therapy to explore its potential effectiveness for patients whose non-Hodgkin lymphoma has returned or hasn't responded to other treatments. ^{6 7 8 9 10}

Who Is on the Research Team?

Michael LaRiviere, MD

Principal Investigator

University of Pennsylvania

Are You a Good Fit for This Trial?

Adults with relapsed/refractory non-Hodgkin lymphoma who have tried at least two prior therapies can join this trial. They must not be pregnant or breastfeeding, agree to use contraception, and have good organ function. Those with a history of certain cancers, severe allergies to pembrolizumab, active infections, or recent immunosuppressive treatments cannot participate.

Inclusion Criteria

- Not a woman of childbearing potential (WOCBP) as defined in Appendix 3 OR

I've had at least 2 treatments for my condition and they didn't work, and I can't have a stem cell transplant.

My cancer can be measured by scans and has grown in previously treated areas.

Exclusion Criteria

I have an autoimmune disease treated with drugs affecting my whole body in the last 2 years.

Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection.

Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pembrolizumab plus low-dose (4 Gy x 5) involved-site radiotherapy

5 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Extension

Pembrolizumab is continued after radiotherapy until disease progression, drug intolerance, or at the discretion of the treating medical oncologist

What Are the Treatments Tested in This Trial?

Interventions

• Low Dose Radiotherapy
• Pembrolizumab

Trial Overview The trial is testing the combination of pembrolizumab (an immune system-boosting drug) with low-dose radiotherapy on patients whose non-Hodgkin lymphoma has returned after treatment or didn't respond to previous treatments. The goal is to see how well this combo works in controlling the disease.

How Is the Trial Designed?

Group I: Pembrolizumab and Radiation Therapy Experimental Treatment 1 Intervention

pembrolizumab plus low-dose (4 Gy x 5) involved-site radiotherapy

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?

Abramson Cancer Center of the University of Pennsylvania

Lead Sponsor

Trials

360

Recruited

108,000+

Abramson Cancer Center at Penn Medicine

Lead Sponsor

Trials

425

Recruited

464,000+

Published Research Related to This Trial

Rituximab has significantly improved outcomes for patients with Non-Hodgkin's lymphoma (NHL), particularly in aggressive forms like diffuse large B cell lymphoma (DLBCL) and follicular lymphoma (FL).

The treatment is generally well-tolerated by patients and has been shown to be cost-effective, making it a valuable option in both initial and relapsed cases of B cell NHL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab in the treatment of non-Hodgkin's lymphoma--a critical evaluation of randomized controlled trials. Griffin, MM., Morley, N.[2020]

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]

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]

In a phase I study involving 67 patients with relapsed/refractory follicular lymphoma and other CD20+ non-Hodgkin lymphomas, the combination of utomilumab and rituximab showed a favorable safety profile, with no dose-limiting toxicities and mostly mild adverse events like fatigue.

The treatment demonstrated clinical activity with an objective response rate of 21.2%, including complete and partial responses, suggesting that the effectiveness may depend on the patient's immune function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-in-Human Study of Utomilumab, a 4-1BB/CD137 Agonist, in Combination with Rituximab in Patients with Follicular and Other CD20+ Non-Hodgkin Lymphomas. Gopal, AK., Levy, R., Houot, R., et al.[2021]

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 study involving 37 patients with relapsed or refractory low-grade or follicular B-cell non-Hodgkin's lymphoma, Rituximab was found to be well tolerated, with most adverse events being mild and decreasing with subsequent infusions.

The treatment resulted in a 57% overall response rate, with 14% achieving a complete response and 43% a partial response, indicating significant clinical activity and suggesting that extended Rituximab treatment may be effective for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Extended Rituximab (anti-CD20 monoclonal antibody) therapy for relapsed or refractory low-grade or follicular non-Hodgkin's lymphoma. Piro, LD., White, CA., Grillo-López, AJ., et al.[2022]

Rituximab, an anti-CD20 monoclonal antibody, demonstrated a 43% overall response rate in a phase II trial involving 31 patients with bulky relapsed or refractory low-grade or follicular non-Hodgkin's lymphoma, indicating its efficacy as a treatment option.

The treatment was well-tolerated, with no patients discontinuing due to adverse events, and it showed a median time to progression of 8.1 months, highlighting its safety and potential for managing this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-agent monoclonal antibody efficacy in bulky non-Hodgkin's lymphoma: results of a phase II trial of rituximab. Davis, TA., White, CA., Grillo-López, AJ., 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]

In a phase II study involving 54 patients with aggressive B-cell lymphomas, rituximab demonstrated significant clinical activity, achieving an overall response rate of 31%, with complete responses in 9% and partial responses in 22% of patients.

The treatment was well-tolerated, with mild adverse events primarily related to infusion syndrome, indicating that rituximab could be a safe option for patients with diffuse large B-cell lymphoma (DLCL) and mantle cell lymphoma (MCL).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab (anti-CD20 monoclonal antibody) for the treatment of patients with relapsing or refractory aggressive lymphoma: a multicenter phase II study. Coiffier, B., Haioun, C., Ketterer, N., et al.[2022]

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]

Citations

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Effectiveness and Safety of Pembrolizumab in Recurrent and ... Although there is currently a high cure rate for cHL, up to 30% of patients in the advanced stages and 5-10% of those in the limited stage ...

2. keytrudahcp.com keytrudahcp.com/efficacy/

Efficacy Data for KEYTRUDA® (pembrolizumab) The most common adverse reactions (≥20%) were decreased appetite (25%), fatigue (25%), dyspnea (23%), and nausea (20%). In KEYNOTE⁠-⁠671, adverse reactions ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT02453594

NCT02453594 | Study of Pembrolizumab (MK-3475) in ... The primary study hypothesis is that treatment with single agent pembrolizumab will result in a clinically meaningful overall response rate. Official Title. A ...

4. ashpublications.org ashpublications.org/blood/article/142/10/878/496370/Five-year-follow-up-of-KEYNOTE-087-pembrolizumab

Five-year follow-up of KEYNOTE-087: pembrolizumab ... Previous analyses of the phase 2 KEYNOTE-087 (NCT02453594) trial of pembrolizumab monotherapy demonstrated effective antitumor activity with ...

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Ten-Year Data for Merck's KEYTRUDA® (pembrolizumab ... KEYTRUDA demonstrated a sustained OS benefit, reducing the risk of death by 29% (HR=0.71 [95% CI, 0.60-0.85]). At 10 years, KEYTRUDA more than ...

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Safety and tolerability of pembrolizumab in patients with ... Eleven patients (61%) experienced drug-related adverse events (mostly grade 1-2); none discontinued treatment due to adverse events. ORR was 41% (7/17); 6 ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT03407144

NCT03407144 | Safety and Efficacy of Pembrolizumab (MK ... This study will examine the safety and efficacy of pembrolizumab (MK-3475) in combination with chemotherapy in children and young adults with newly diagnosed ...

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40148307/

Clinical Efficacy and Safety of Pembrolizumab Therapy for ... The study findings revealed a Disease Control Rate (DCR) of 63%, Overall Response Rate (ORR) of 42%, Complete Response Rate (CRR) of 23%, and 1- ...

9. merck.com merck.com/news/five-year-data-for-mercks-keytruda-pembrolizumab-plus-chemotherapy-showed-sustained-survival-benefit-versus-chemotherapy-alone-in-two-studies-for-metastatic-non-small-cell-lung-cancer-nsclc/

Five-Year Data for Merck's KEYTRUDA® (pembrolizumab ... Five-year overall survival rate of 19.4% and 18.4% for KEYTRUDA plus chemotherapy in KEYNOTE-189 and KEYNOTE-407, respectively.

10. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.7517

Efficacy and safety of pembrolizumab every six weeks in ... Pembrolizumab (pembro) 200 mg Q3W demonstrated robust antitumor activity and manageable safety in relapsed/refractory (R/R) classical Hodgkin lymphoma (cHL)