Pembrolizumab + Brentuximab Vedotin for Hodgkin's Lymphoma

Recruiting at 21 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two new drugs, Brentuximab vedotin (Adcetris) and Pembrolizumab (KEYTRUDA), to determine their effectiveness in shrinking or eliminating classical Hodgkin's lymphoma, a cancer affecting the lymphatic system. Researchers aim to discover if these drugs can benefit individuals who have undergone chemotherapy but still have the disease. The trial compares these drugs with another treatment option to identify the more effective approach. Suitable participants are those with classical Hodgkin's lymphoma that did not improve with initial chemotherapy and are considering further treatment options. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering a chance to explore new treatment possibilities.

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.

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

Research shows that patients generally tolerate pembrolizumab and brentuximab vedotin well. The FDA has approved pembrolizumab for treating classical Hodgkin's lymphoma, indicating it meets specific safety standards. Studies have found that pembrolizumab can improve quality of life more than brentuximab vedotin for patients with relapsed or hard-to-treat classical Hodgkin's lymphoma. While both treatments show promise, some side effects have been reported, so discussing these with a doctor is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about combining Brentuximab vedotin and Pembrolizumab for Hodgkin's Lymphoma because these treatments offer a unique approach compared to standard options like ABVD (Adriamycin, bleomycin, vinblastine, and dacarbazine) or BEACOPP. Brentuximab vedotin is an antibody-drug conjugate that specifically targets cancer cells expressing the CD30 protein, delivering a potent cytotoxic agent directly to them. Pembrolizumab, on the other hand, is an immune checkpoint inhibitor that boosts the body's immune response against cancer cells by blocking the PD-1 pathway. This combination targets the cancer both by directly attacking it and by empowering the immune system, potentially offering a more effective and comprehensive treatment strategy.

What evidence suggests that this trial's treatments could be effective for Hodgkin's Lymphoma?

Research has shown that using brentuximab vedotin and pembrolizumab together may help treat classical Hodgkin's lymphoma. In this trial, one group of participants will receive this combination. Studies have found that pembrolizumab alone improved patients' quality of life more than brentuximab vedotin in those whose disease returned or didn't respond to treatment. Another study showed that pembrolizumab helped patients live longer without their disease worsening compared to using brentuximab vedotin alone. Together, these drugs aim to shrink or eliminate the cancer. Early results suggest this combination might be an effective treatment option for people with Hodgkin's lymphoma. ^{1 2 4 6 7}

Who Is on the Research Team?

John Kuruvilla

Principal Investigator

University Health Network, Princess Margaret Hospital

Kerry Savage

Principal Investigator

BCCA-Vancouver Cancer Centre

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8791579/

Quality-of-life analysis of pembrolizumab vs brentuximab ... Key Points. Pembrolizumab improved health-related quality of life over brentuximab vedotin in patients with relapsed/refractory cHL.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8869808/

Brentuximab Vedotin and Pembrolizumab Combination in ... In this retrospective study, we evaluated the efficacy of a combination of brentuximab vedotin (BV) and pembrolizumab in a series of HL patients ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT02684292

NCT02684292 | Study of Pembrolizumab (MK-3475) vs. ... The purpose of this study is to evaluate pembrolizumab (MK-3475) in the treatment of participants with relapsed or refractory Classical Hodgkin Lymphoma.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05180097

NCT05180097 | Pembrolizumab and Brentuximab Vedotin ... This study is being done to determine if two new drugs can shrink or eliminate classical Hodgkins lymphoma. Detailed Description. Treatment given to ...

5. merck.com merck.com/news/mercks-keytruda-pembrolizumab-significantly-improved-progression-free-survival-compared-with-brentuximab-vedotin-in-patients-with-relapsed-or-refractory-classical-hodgkin-lymphoma-ch/

Merck's KEYTRUDA® (pembrolizumab) Significantly ... KEYTRUDA demonstrated a statistically significant and clinically meaningful improvement in PFS compared with brentuximab vedotin (BV) in this patient ...

6. ashpublications.org ashpublications.org/bloodadvances/article/8/11/2740/515346/Brentuximab-vedotin-and-chemotherapy-in-relapsed

Brentuximab vedotin and chemotherapy in relapsed/refractory ... In patients with relapsed disease, the BV cohort showed a significantly better 3-year PFS than the chemotherapy cohort of 79.9% (95% CI, 74-87) vs 69.7% (95% ...

7. fda.gov fda.gov/drugs/resources-information-approved-drugs/pembrolizumab-keytruda-classical-hodgkin-lymphoma

Pembrolizumab (KEYTRUDA) for classical Hodgkin ... The recommended dose and schedule of pembrolizumab for cHL is 200 mg every 3 weeks for adults and 2 mg/kg (up to 200 mg) every 3 weeks for pediatric patients.