Pembrolizumab + Brentuximab Vedotin for Hodgkin's Lymphoma

Recruiting at 19 trial locations

Overseen By Annette Hay

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Canadian Cancer Trials Group

Must not be taking: Steroids, Immunosuppressants

Disqualifiers: Peripheral neuropathy, Active CNS disease, HIV, 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

Compensation: Varies

Number of Visits: Unknown

Duration: 8-12 weeks

84 Participants Needed

Trial Summary

What is the purpose of this trial?

This study is being done to determine if two new drugs can shrink or eliminate classical Hodgkins 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, if you are on systemic steroid therapy or other immunosuppressive treatments, you may need to stop them before starting the trial. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug combination Pembrolizumab and Brentuximab Vedotin for Hodgkin's Lymphoma?

Research shows that the combination of Pembrolizumab and Brentuximab Vedotin is effective for patients with relapsed or hard-to-treat Hodgkin's Lymphoma, with a study reporting an 80% complete remission rate. Additionally, Pembrolizumab alone has shown antitumor activity, and Brentuximab Vedotin has a high response rate in similar conditions. ^{1 2 3 4 5}

Is the combination of Pembrolizumab and Brentuximab Vedotin safe for humans?

Brentuximab Vedotin is generally well tolerated, but common side effects include peripheral neuropathy (nerve damage causing pain or numbness), diarrhea, nausea, anemia (low red blood cell count), and fatigue. Pembrolizumab, used for similar conditions, can cause immune-related side effects like skin rash, colitis (inflammation of the colon), and lung issues. Both drugs have been used safely in humans, but they can have serious side effects. ^{1 2 6 7 8}

How is the drug combination of Pembrolizumab and Brentuximab Vedotin unique for treating Hodgkin's Lymphoma?

The combination of Pembrolizumab and Brentuximab Vedotin is unique because it pairs an immune checkpoint inhibitor (Pembrolizumab) with an antibody-drug conjugate (Brentuximab Vedotin) to target and destroy cancer cells, offering a novel approach for patients with relapsed or refractory Hodgkin's Lymphoma who have not responded to other treatments. ^{1 2 3 5 9}

Research Team

Kerry Savage

Principal Investigator

BCCA-Vancouver Cancer Centre

John Kuruvilla

Principal Investigator

University Health Network, Princess Margaret Hospital

Eligibility Criteria

Adults with relapsed or refractory classic Hodgkin lymphoma after anthracycline chemotherapy, eligible for stem cell transplant. Must have a life expectancy over 90 days, stable organ function, and no severe active infections or immune conditions. Participants need to consent to treatment protocols and be willing to use effective contraception.

Inclusion Criteria

Life expectancy > 90 days

I am fully active or can carry out light work.

I can and will fill out health questionnaires in English or French.

Exclusion Criteria

I do not have any severe health conditions that could make treatment unsafe for me.

I have not had radiotherapy in the last 2 weeks.

I have had a stroke or brain blood vessel event.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either Pembrolizumab and Brentuximab Vedotin or GDP as salvage treatment for relapsed/refractory classical Hodgkin lymphoma

8-12 weeks

High Dose Chemotherapy and Autologous Stem Cell Transplantation

Participants undergo high dose chemotherapy followed by autologous stem cell transplantation

4-6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Treatment Details

Interventions

• Brentuximab vedotin
• Pembrolizumab

Trial Overview The trial is testing if Pembrolizumab and Brentuximab Vedotin are more effective than the GDP regimen (Dexamethasone, Cisplatin, Gemcitabine) followed by a stem cell transplant in shrinking or eliminating Hodgkin lymphoma.

Participant Groups

Group I: GDP Active Control 3 Interventions

Group II: Brentuximab vedotin + Pembrolizumab Active Control 2 Interventions

Brentuximab vedotin is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Adcetris for:

• Hodgkin lymphoma
• Systemic anaplastic large cell lymphoma
• Cutaneous T-cell lymphoma

Approved in United States as Adcetris for:

• Classical Hodgkin lymphoma
• Systemic anaplastic large cell lymphoma
• Primary cutaneous anaplastic large cell lymphoma
• Mycosis fungoides

Approved in Canada as Adcetris for:

• Hodgkin lymphoma
• Systemic anaplastic large cell lymphoma

Approved in Japan as Adcetris for:

• Hodgkin lymphoma
• Anaplastic large cell lymphoma

Who Is Running the Clinical Trial?

Canadian Cancer Trials Group

Lead Sponsor

Trials

135

Recruited

70,300+

Pfizer

Industry Sponsor

Trials

4,712

Recruited

50,980,000+

Known For

Vaccine Innovations

Top Products

Viagra, Zoloft, Lipitor, Prevnar 13

Albert Bourla

Pfizer

Chief Executive Officer since 2019

PhD in Biotechnology of Reproduction, Aristotle University of Thessaloniki

Patrizia Cavazzoni

Pfizer

Chief Medical Officer

MD from McGill University

Australasian Leukaemia and Lymphoma Group

Collaborator

Trials

17

Recruited

4,300+

Seagen Inc.

Industry Sponsor

Trials

212

Recruited

73,800+

Founded

1997

Headquarters

Bothell, USA

Known For

Antibody-Drug Conjugates

Top Products

Adcetris (brentuximab vedotin), Tukysa (tucatinib), Padcev (enfortumab vedotin-ejfv), Tivdak (tisotumab vedotin-tftv)

Dr. Roger Dansey

Seagen Inc.

Chief Medical Officer since 2018

MD from University of Witwatersrand

David R. Epstein

Seagen Inc.

Chief Executive Officer since 2022

BSc in Pharmacy from Rutgers University, MBA from Columbia University

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Findings from Research

In a phase 3 study involving 304 patients with relapsed or refractory classical Hodgkin lymphoma, pembrolizumab demonstrated a median progression-free survival of 13.2 months, significantly longer than the 8.3 months observed with brentuximab vedotin, indicating its superior efficacy.

While both treatments had associated adverse events, pembrolizumab's safety profile was consistent with previous studies, with serious treatment-related events occurring in 16% of patients, supporting its use as a preferred option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab versus brentuximab vedotin in relapsed or refractory classical Hodgkin lymphoma (KEYNOTE-204): an interim analysis of a multicentre, randomised, open-label, phase 3 study. Kuruvilla, J., Ramchandren, R., Santoro, A., et al.[2021]

Brentuximab vedotin demonstrated a high overall objective response rate of 75% in 102 patients with relapsed Hodgkin lymphoma and 86% in 58 patients with relapsed systemic anaplastic large cell lymphoma, indicating its efficacy as a targeted treatment.

The treatment was generally well tolerated, with peripheral neuropathy being the most common side effect; however, about half of the patients who experienced this side effect saw complete resolution.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brentuximab vedotin: a review of its use in patients with hodgkin lymphoma and systemic anaplastic large cell lymphoma following previous treatment failure. Garnock-Jones, KP.[2021]

A patient with relapsed/refractory Hodgkin's lymphoma showed a remarkable and durable response to the combination of brentuximab-vedotin and pembrolizumab, even after failing multiple previous treatments.

This case highlights the potential of combining novel agents like BV and immune checkpoint inhibitors to improve treatment outcomes in difficult-to-treat Hodgkin's lymphoma, suggesting further research is warranted.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prolonged Remission by Pembrolizumab and Brentuximab-Vedotin Combination Therapy in Heavily-Pretreated Relapsed/Refractory Hodgkin's Lymphoma. Yu, TY., Dai, MS.[2020]

In a study of 10 high-risk relapsed/refractory Hodgkin lymphoma patients, the combination of brentuximab vedotin and pembrolizumab led to an impressive 80% complete metabolic remission rate, allowing most patients to proceed to autologous stem cell transplantation.

This treatment approach shows promise as an effective bridge to ASCT, although 20% of patients experienced progressive disease, highlighting the need for ongoing monitoring and potential alternative strategies for those who do not respond.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brentuximab Vedotin and Pembrolizumab Combination in Patients with Relapsed/Refractory Hodgkin Lymphoma: A Single-Centre Retrospective Analysis. Massaro, F., Meuleman, N., Bron, D., 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]

Brentuximab vedotin is an effective treatment for Hodgkin's lymphoma that has not responded to standard chemotherapy, as it specifically targets cancer cells expressing CD30 markers with a cytotoxic agent.

However, it can cause serious adverse effects, including rare cases of diabetic ketoacidosis and profound insulin resistance, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diabetic Ketoacidosis and Profound Insulin Resistance From Brentuximab Vedotin. Thakkar, K., Khurana, S., Sun, Y., et al.[2023]

Brentuximab vedotin, a targeted therapy for Hodgkin lymphoma, is effective for patients at high risk of recurrence or relapse, but it can cause significant side effects, particularly peripheral neuropathy.

For patients who relapse after brentuximab vedotin, anti-PD1 immunotherapy (nivolumab or pembrolizumab) is an option, though it carries unpredictable immune-related side effects, highlighting the need for careful management in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Toxicity of targeted therapies and immunotherapy with checkpointinhibitors in Hodgkin lymphoma]. Michot, JM., Lazarovici, J.[2023]

Brentuximab vedotin, an antibody-drug conjugate, does not cause significant prolongation of the QT/QTc interval, indicating a favorable cardiac safety profile in patients with CD30-positive hematologic malignancies.

In a phase 1 study involving 52 patients, brentuximab vedotin was well tolerated, with no clinically meaningful changes in cardiac repolarization and a response rate consistent with previous trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brentuximab vedotin does not cause clinically relevant QTc interval prolongation in patients with CD30-positive hematologic malignancies. Han, TH., Chen, R., Advani, R., et al.[2021]

Brentuximab vedotin is an effective treatment for adult patients with relapsed or refractory CD30+ Hodgkin lymphoma and systemic anaplastic large cell lymphoma, showing objective response rates of 75% in Hodgkin lymphoma and 86% in systemic anaplastic large cell lymphoma based on studies involving 160 patients.

The treatment works by targeting the CD30 receptor on cancer cells, delivering the cytotoxic agent MMAE directly to the tumor, and is associated with manageable side effects such as peripheral sensory neuropathy and fatigue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The European Medicines Agency Review of Brentuximab Vedotin (Adcetris) for the Treatment of Adult Patients With Relapsed or Refractory CD30+ Hodgkin Lymphoma or Systemic Anaplastic Large Cell Lymphoma: Summary of the Scientific Assessment of the Committee for Medicinal Products for Human Use. Gravanis, I., Tzogani, K., van Hennik, P., et al.[2019]

References

1. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab versus brentuximab vedotin in relapsed or refractory classical Hodgkin lymphoma (KEYNOTE-204): an interim analysis of a multicentre, randomised, open-label, phase 3 study. [2021]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Brentuximab vedotin: a review of its use in patients with hodgkin lymphoma and systemic anaplastic large cell lymphoma following previous treatment failure. [2021]

3. Canada pubmed.ncbi.nlm.nih.gov

Prolonged Remission by Pembrolizumab and Brentuximab-Vedotin Combination Therapy in Heavily-Pretreated Relapsed/Refractory Hodgkin's Lymphoma. [2020]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Brentuximab Vedotin and Pembrolizumab Combination in Patients with Relapsed/Refractory Hodgkin Lymphoma: A Single-Centre Retrospective Analysis. [2022]

5. England 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. [2019]

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

Diabetic Ketoacidosis and Profound Insulin Resistance From Brentuximab Vedotin. [2023]

7. France pubmed.ncbi.nlm.nih.gov

[Toxicity of targeted therapies and immunotherapy with checkpointinhibitors in Hodgkin lymphoma]. [2023]

8. Germany pubmed.ncbi.nlm.nih.gov

Brentuximab vedotin does not cause clinically relevant QTc interval prolongation in patients with CD30-positive hematologic malignancies. [2021]

9. England pubmed.ncbi.nlm.nih.gov

The European Medicines Agency Review of Brentuximab Vedotin (Adcetris) for the Treatment of Adult Patients With Relapsed or Refractory CD30+ Hodgkin Lymphoma or Systemic Anaplastic Large Cell Lymphoma: Summary of the Scientific Assessment of the Committee for Medicinal Products for Human Use. [2019]