Pembrolizumab + Radiation Therapy for Hodgkin's Lymphoma

Not currently recruiting at 8 trial locations

Overseen By Joachim Yahalom, MD

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Stage III/IV, Bulky disease, 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: 4

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of the drug pembrolizumab (KEYTRUDA) combined with Involved Site Radiation Therapy for patients with a specific type of Hodgkin lymphoma that has recurred or did not fully respond to initial treatment. The goal is to determine if this combination can effectively treat the disease while avoiding harsher treatments like larger radiation fields or additional chemotherapy. Suitable candidates include those with early-stage Hodgkin lymphoma that has relapsed or did not fully respond to previous chemotherapy, provided their symptoms are not severe and their tumors are not too large. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of participants, offering a chance to benefit from a potentially effective therapy.

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop taking your current medications. However, you cannot have had chemotherapy, targeted therapy, or radiation within 2 weeks before starting the trial, and you should not be on systemic steroid therapy or immunosuppressive therapy within 7 days before the trial begins.

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

Research has shown that pembrolizumab is generally safe for people with classical Hodgkin lymphoma. In one study, 69% of patients responded well to pembrolizumab, indicating its effectiveness. Some side effects, such as tiredness and fever, were reported but were usually manageable.

For involved site radiation therapy, the safety data is also encouraging. Evidence suggests it causes fewer long-term side effects compared to older methods. Only about 5% of people experienced side effects that appeared after treatment ended, which is relatively low.

Overall, both treatments have been well-tolerated in past studies, with side effects that can usually be managed. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments for Hodgkin's Lymphoma?

Pembrolizumab is unique because it harnesses the power of the immune system to fight Hodgkin's Lymphoma by blocking the PD-1 pathway, which cancers often exploit to hide from immune cells. This mechanism is different from traditional chemotherapy and radiation, which directly target cancer cells but can also affect healthy cells. Researchers are excited about pembrolizumab because it offers a more targeted approach, potentially resulting in fewer side effects while maintaining effectiveness. Additionally, combining pembrolizumab with radiation therapy might enhance the treatment's impact, offering a promising new avenue for patients who may not respond as well to conventional treatments.

What evidence suggests that pembrolizumab and involved site radiation therapy could be effective for Hodgkin's lymphoma?

Research has shown that pembrolizumab effectively treats classical Hodgkin lymphoma, with studies finding that 69% of patients respond to this treatment, experiencing either partial or complete improvement. Many of these patients continue to do well for several years. In this trial, participants will receive a combination of pembrolizumab and targeted radiation therapy, known as involved site radiotherapy. This combination might offer a strong treatment option for those whose Hodgkin lymphoma has returned or is not responding to other treatments, as involved site radiotherapy alone has shown survival rates reaching up to 95% for some patients. ^{1 2 3 6 7}

Who Is on the Research Team?

Alison Moskowitz, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults over 18 with early stage classical Hodgkin lymphoma that has either come back or didn't respond to initial treatment. They should have had only one prior therapy, be in good health with proper organ function, and not have active infections like HIV or hepatitis. Women of childbearing age must test negative for pregnancy and agree to contraception.

Inclusion Criteria

I was initially diagnosed with early stage cancer, treated with chemotherapy, and my cancer did not fully respond but hasn't grown larger than 10 cm.

My kidney function, measured by creatinine or GFR, is within the required range.

Hematologic criteria: ANC ≥1,000 /mcL, Platelets ≥75,000 / mcL, Hemoglobin ≥8 g/dL

Exclusion Criteria

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

I have received more than one treatment for Hodgkin lymphoma.

I haven't had cancer treatment or recovered from its side effects in the last 2 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pembrolizumab 200mg IV on day 1 of each 21-day cycle for a total of 4 cycles

12 weeks

4 visits (in-person)

Radiation

Participants receive involved site radiotherapy (ISRT) based on PET/CT results and biopsy outcomes

2-3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Involved Site Radiation Therapy
• Pembrolizumab

Trial Overview

The study tests pembrolizumab (a drug that helps the immune system fight cancer) followed by involved site radiation therapy (targeted radiation). It aims to see if this combo can cure relapsed/refractory Hodgkin lymphoma without the side effects of extensive chemotherapy or stem cell transplant.

How Is the Trial Designed?

Group I: Pembrolizumab and Involved Site Radiation Therapy Experimental Treatment 2 Interventions

Following a PET/CT simulation to evaluate the extent of disease, pembrolizumab 200mg IV will be given over 30 minutes on day 1 of each 21 day cycle for a total of 4 cycles. Fourteen to 21 days after the completion of therapy, a PET/CT simulation will be repeated. Pts with complete response will proceed to 20 Gy of ISRT. Pts without a PET CR, but improvement on CT scan will have a repeat biopsy. If the biopsy is negative for Hodgkin Lymphoma, these ps will receive 30 Gy of ISRT. If the biopsy is positive for Hodgkin Lymphoma, they will receive 36-40 Gy ISRT. Pts without a PET CR, but improvement on CT scan will have a repeat biopsy. If the biopsy is negative for Hodgkin Lymphoma, these pts will receive 30 Gy of ISRT. If the biopsy is positive for Hodgkin Lymphoma, they will receive 36-40 Gy ISRT. Pts with new sites of disease or progression on imaging will have a repeat biopsy, per treating physician's discretion \& then be treated off 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?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Published Research Related to This Trial

A 74-year-old woman with lung adenocarcinoma developed fatal immune thrombocytopenia after receiving pembrolizumab following radiotherapy, highlighting a potential risk of severe immune-related adverse events (irAEs) when combining these treatments.

Flow cytometry analysis showed increased PD-1 and Ki-67 expression in T cells post-radiotherapy, suggesting that radiotherapy may enhance immune activation and contribute to the development of irAEs in patients undergoing anti-PD-1 therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab-related Immune Thrombocytopenia in a Patient with Lung Adenocarcinoma Treated by Radiotherapy: Potential Immune-related Adverse Event Elicited by Radiation Therapy. Tamanoi, D., Saruwatari, K., Imamura, K., et al.[2022]

In a pooled analysis of 148 patients with metastatic non-small-cell lung cancer, adding radiotherapy to pembrolizumab significantly improved the best out-of-field response rate (41.7% vs 19.7%) and best disease control rate (65.3% vs 43.4%), indicating enhanced efficacy of the combination treatment.

Patients receiving the combination therapy also experienced longer median progression-free survival (9.0 months vs 4.4 months) and overall survival (19.2 months vs 8.7 months) compared to those receiving pembrolizumab alone, with no new safety concerns identified.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab with or without radiotherapy for metastatic non-small-cell lung cancer: a pooled analysis of two randomised trials. Theelen, WSME., Chen, D., Verma, V., et al.[2021]

In a phase II study involving 210 patients with relapsed or refractory classic Hodgkin lymphoma, pembrolizumab showed a high overall response rate of 69%, indicating its effectiveness as a treatment option.

The safety profile of pembrolizumab was consistent with previous studies, suggesting it is a well-tolerated therapy for patients with this challenging form of lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II Study of the Efficacy and Safety of Pembrolizumab for Relapsed/Refractory Classic Hodgkin Lymphoma. Chen, R., Zinzani, PL., Fanale, MA., 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]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating advanced melanoma, showing an overall response rate of 24% in a trial of 89 patients, with 86% of responses lasting at least 6 months.

While there are potential immune-mediated side effects, the benefits of prolonged tumor response durations were deemed to outweigh these risks, marking an improvement over existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. Chuk, MK., Chang, JT., Theoret, MR., et al.[2021]

Pembrolizumab is a monoclonal antibody that effectively blocks the PD-1 receptor on T cells, enhancing their ability to attack cancer cells, particularly in melanoma patients.

In a Phase I study involving 411 patients, pembrolizumab demonstrated high durable response rates with minimal toxicity, indicating its potential as a safe and effective treatment option for melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab joins the anti-PD-1 armamentarium in the treatment of melanoma. Hersey, P., Gowrishankar, K.[2017]

In a study of 98 patients with advanced non-small-cell lung cancer (NSCLC), those who had previously received radiotherapy experienced significantly longer progression-free survival (4.4 months) and overall survival (10.7 months) when treated with pembrolizumab compared to those without prior radiotherapy.

The safety profile was acceptable, with similar rates of severe pulmonary toxicity between patients who had and had not received thoracic radiotherapy, suggesting that combining radiotherapy with pembrolizumab may be a beneficial treatment strategy for NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Previous radiotherapy and the clinical activity and toxicity of pembrolizumab in the treatment of non-small-cell lung cancer: a secondary analysis of the KEYNOTE-001 phase 1 trial. Shaverdian, N., Lisberg, AE., Bornazyan, K., et al.[2022]

In a phase 2 study involving 216 patients with stage III non-small cell lung cancer (NSCLC), the combination of pembrolizumab and concurrent chemoradiation therapy (cCRT) showed a high objective response rate of approximately 70.5% in cohort A and 70.6% in cohort B, indicating strong antitumor activity.

The treatment was associated with manageable safety, with grade 3 or higher pneumonitis occurring in 8.0% of cohort A and 6.9% of cohort B, suggesting that while there are risks, the benefits of this treatment approach may outweigh them for patients with locally advanced NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab Plus Concurrent Chemoradiation Therapy in Patients With Unresectable, Locally Advanced, Stage III Non-Small Cell Lung Cancer: The Phase 2 KEYNOTE-799 Nonrandomized Trial. Jabbour, SK., Lee, KH., Frost, N., et al.[2022]

In a study of 55 patients with relapsed/refractory Hodgkin's Lymphoma, Pembrolizumab showed a high response rate of 74.5%, with a complete response in 32.7% of patients, indicating its efficacy before autologous stem cell transplantation.

The 12-month overall survival rate was 92%, and the progression-free survival rate was 51%, demonstrating reasonable safety and promising survival outcomes for patients treated with checkpoint inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the Treatment of Relapsed and Refractory Classical Hodgkin Lymphoma After Autologous Transplant and in Transplant-Naïve Patients. Halahleh, K., Al Sawajneh, S., Saleh, Y., et al.[2022]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating unresectable or metastatic melanoma based on two clinical trials involving 1,374 patients, showing significant improvements in overall survival compared to ipilimumab, with hazard ratios indicating a reduced risk of death.

Patients receiving pembrolizumab also experienced significant improvements in progression-free survival, although some immune-mediated adverse reactions like hypothyroidism and pneumonitis were noted, highlighting the importance of monitoring for side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. Barone, A., Hazarika, M., Theoret, MR., et al.[2022]

Pembrolizumab, an immunotherapy targeting PD-1, showed limited effectiveness in a patient with metastatic renal cell carcinoma, highlighting that only 20-40% of patients benefit from such treatments due to individual tumor biology and immune checkpoint diversity.

The patient's rapid disease progression during treatment may be linked to a lack of tumor-infiltrating lymphocytes (TILs) and the specific radiation dose and schedule used, which could affect the tumor microenvironment and the potential synergy with pembrolizumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune biomarkers of treatment failure for a patient on a phase I clinical trial of pembrolizumab plus radiotherapy. Alexander, GS., Palmer, JD., Tuluc, M., 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]

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