Pembrolizumab + Brentuximab Vedotin for Hodgkin's Lymphoma

Recruiting in Palo Alto (17 mi)

+16 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Canadian Cancer Trials Group

Must not be taking: Steroids, Immunosuppressants

Disqualifiers: Peripheral neuropathy, Active CNS disease, HIV, others

No Placebo Group

Prior Safety Data

Breakthrough Therapy

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}

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.

Trial 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 (Monoclonal Antibodies)
• Pembrolizumab (Monoclonal Antibodies)

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Allan Blair Cancer Centre Regina, Canada

CIUSSS de l'Estrie - Centre hospitalier Sherbrooke, Canada

Verspeeten Family Cancer Centre London, Canada

Arthur J.E. Child Comprehensive Cancer Centre Calgary, Canada

More Trial Locations

Who Is Running the Clinical Trial?

Canadian Cancer Trials Group Lead Sponsor

Pfizer Industry Sponsor

Australasian Leukaemia and Lymphoma Group Collaborator

Seagen Inc. Industry Sponsor

Merck Sharp & Dohme LLC Industry Sponsor

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] PD-1 blockade via pembrolizumab monotherapy has shown antitumour activity and toxicity in patients with relapsed or refractory classical Hodgkin lymphoma. Here, we present interim analyses from the KEYNOTE-204 study evaluating pembrolizumab versus brentuximab vedotin for relapsed or refractory classical Hodgkin lymphoma.

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] Brentuximab vedotin (ADCETRIS(®)) is an antibody-drug conjugate that is specifically targeted against CD30-positive cancer cells such as those in Hodgkin lymphoma or systemic anaplastic large cell lymphoma (ALCL). Intravenous brentuximab vedotin was associated with an overall objective response rate (primary endpoint) of 75 % in 102 patients with Hodgkin lymphoma who had relapsed after high-dose chemotherapy and autologous haematopoietic stem cell transplantation, in a noncomparative, multicentre, phase II trial. In 58 patients with relapsed systemic ALCL after at least one prior treatment, intravenous brentuximab vedotin was associated with an overall objective response rate (primary endpoint) of 86 % in a noncomparative, multicentre, phase II trial. Tumour reductions were observed in 94 % of patients with Hodgkin lymphoma and 97 % of patients with systemic ALCL, and most tumours decreased in size by >65 % and >85 %, respectively. The estimated 12-month survival rates were 89 % and 52 %, respectively. Brentuximab vedotin was generally well tolerated in these trials. The most common adverse event was peripheral neuropathy; approximately one-half of patients with this adverse event experienced complete resolution.

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] Hodgkin's lymphoma (HL) is usually sensitive and curative to multi-agent chemotherapy, but may become refractory disease in a subset of relapsed patients. Recent novel agents, brentuximab-vedotin (BV) and immune checkpoint inhibitors have significantly improve the treatment outcome. We report the outcome by combination of BV with pembrolizumab in a patient with a relapsed/refractory HL in a remarkable and durable response, even previously failed to multiple lines of chemotherapy, or brentuximab-vedotin/pembrolizumab monotherapy. Further investigation of immunotherapy combination in relapsed/refractory HL is needed.

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] Classical Hodgkin lymphoma (HL) patients presenting a relapsed/refractory (R/R) disease are currently managed with salvage chemotherapy followed by autologous stem cell transplantation (ASCT). However, almost 25-30% of these patients fail to achieve a complete response (CR) with standard salvage regimens. In this retrospective study, we evaluated the efficacy of a combination of brentuximab vedotin (BV) and pembrolizumab in a series of HL patients presenting with a high-risk, multi-refractory disease. Patients achieving a Deauville score ≤4 proceeded to ASCT consolidation. After ASCT, patients received BV as maintenance for a total of 16 administrations. We collected data from 10 patients with a median age of 30.7 years. At a median follow-up of 16.5 months, we reported a complete metabolic remission (CMR) in eight patients (80%), with seven patients (70%) directly proceeding to ASCT (the other two patients in CMR are still undergoing treatment). BV consolidation was started in six patients and completed by three patients (one ongoing, two interruption). Two patients (20%) presented a progressive disease (PD) and subsequently died, while the others are still in CMR. The BV and pembrolizumab combination is a very effective bridge treatment to ASCT for high-risk R/R HL patients.

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] There is significant unmet need among patients with relapsed and refractory classical Hodgkin's lymphoma (RRcHL) who have failed multiple lines of therapy, including brentuximab vedotin (BV). Pembrolizumab, an immune checkpoint inhibitor, is one possible treatment solution for this population.

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

Diabetic Ketoacidosis and Profound Insulin Resistance From Brentuximab Vedotin. [2023] Hodgkin's lymphoma is commonly treated with a combination of chemotherapy drugs including doxorubicin, bleomycin, vinblastine, and dacarbazine. Antibody-drug conjugates such as brentuximab vedotin are now being used to treat Hodgkin's lymphoma that has not responded to standard treatment. Brentuximab vedotin is a monoclonal antibody that selectively delivers a cytotoxic agent, monomethyl auristatin E, which targets cells expressing surface CD30 markers, a protein that may be found in high amounts in some cancer cells including lymphoma cells. Common adverse effects of the drug include diarrhea, nausea, anemia, and fatigue. We present a case of a patient with diabetic ketoacidosis and profound insulin resistance secondary to brentuximab. Diabetic ketoacidosis is a rare but serious adverse reaction in this growing class of antibody-drug conjugates.

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

[Toxicity of targeted therapies and immunotherapy with checkpointinhibitors in Hodgkin lymphoma]. [2023] TOXICITY OF TARGETED THERAPIES AND IMMUNOTHERAPY WITH CHECKPOINT INHIBITORS IN HODGKIN LYMPHOMA. In patients at increased risk of recurrence or progression after autotransplantation, or in cases of relapse after autotransplantation or after at least two lines of treatment when intensive multidrug therapy is no longer a treatment option, targeted anti-CD30 therapy with brentuximab vedotin may be proposed. Brentuximab vedotin is a monoclonal antibody directed against CD30 and coupled with an anti-microtubule cytotoxic agent, monomethyl auristatin E (MMAE). The main adverse side effect of brentuximab vedotin is peripheral neuropathy. In patients who have relapsed after intensive chemotherapy, including autograft for patients eligible for this treatment, and after failure of brentuximab vedotin, anti-PD1 immunotherapy (nivolumab or pembrolizumab) may be offered. Anti-PD1 (Programmed cell death protein 1) side effects are immune-related, varied and unpredictable (endocrinopathies, rash, colitis, interstitial lung disease). The tolerability profiles of brentuximab vedotin and anti-PD1 and the management of the main undesirable side effects of these treatments are detailed for clinical practice.

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] Brentuximab vedotin (ADCETRIS®), an antibody-drug conjugate, comprises an anti-CD30 antibody conjugated by a protease-cleavable linker to a microtubule-disrupting agent, monomethyl auristatin E (MMAE). In vitro studies showed that MMAE does not interfere with hERG K+ channels at clinically relevant concentrations. In pivotal phase 2 clinical trials in patients with relapsed or refractory Hodgkin lymphoma and systemic anaplastic large cell lymphoma, brentuximab vedotin has shown substantial efficacy and an acceptable safety profile. This phase 1 open-label study was designed to evaluate the effect of brentuximab vedotin on the duration of cardiac ventricular repolarization.

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] On October 25, 2012, a conditional marketing authorization valid throughout the European Union (EU) was issued for brentuximab vedotin for the treatment of adult patients with relapsed or refractory CD30+ Hodgkin lymphoma (HL) and for the treatment of adult patients with relapsed or refractory systemic anaplastic large cell lymphoma (sALCL). For HL, the indication is restricted to treatment after autologous stem cell transplantation (ASCT) or after at least two previous therapies when ASCT or multiagent chemotherapy is not a treatment option.