Pembrolizumab + Brentuximab for T-Cell Lymphoma

Recruiting at 1 trial location

Overseen By Stephanie Ladd, BS

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Yale University

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

Disqualifiers: HIV, Hepatitis B, Hepatitis C, 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: 35 cycles

32 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of two drugs, pembrolizumab and brentuximab (also known as Adcetris), to evaluate their effectiveness for people with certain types of T-cell lymphoma that have not responded to previous treatments. The goal is to determine if this drug combination can help at least 55% of participants. It targets individuals with CD30-positive T-cell lymphoma, which includes various subtypes, who have experienced a recurrence of the disease or did not respond to at least one prior therapy. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications. However, it allows the concurrent use of certain medications like bexarotene or vorinostat for CTCL if the dose has been stable for 8 weeks before starting the trial. It's best to discuss your current medications with the trial team.

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

Research shows that the combination of brentuximab vedotin and pembrolizumab is being tested for safety in treating T-cell lymphoma. Previous studies have found that brentuximab vedotin, which targets a protein on cancer cells, and pembrolizumab, an immunotherapy drug, can be used together. These studies suggest that the combination is generally well-tolerated by patients.

Reports from earlier trials did not show any unusual or severe side effects beyond what is typically expected for cancer treatments. Common side effects may include tiredness, nausea, and mild skin reactions. However, each person's experience can vary.

It's important to remember that this treatment is in a mid-stage trial, so more information about its safety is still being gathered. This phase usually involves more participants than earlier trials, helping researchers better understand its safety. As always, discussing any concerns with a healthcare provider is crucial before joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combinatorial treatment of pembrolizumab and brentuximab vedotin for T-cell lymphoma because it targets the cancer in a unique way. Unlike traditional chemotherapy that attacks rapidly dividing cells, brentuximab vedotin is an antibody-drug conjugate that specifically targets CD30-expressing cancer cells, delivering a potent drug directly to the tumor. Pembrolizumab, on the other hand, is an immune checkpoint inhibitor that helps the immune system recognize and attack cancer cells. This combination could potentially enhance the body's ability to fight the cancer more effectively than current treatments.

What evidence suggests that pembrolizumab and brentuximab might be an effective treatment for T-cell lymphoma?

Research has shown that using pembrolizumab with brentuximab vedotin may effectively treat a type of T-cell lymphoma that has returned or is not responding to treatment. In this trial, participants will receive a combination of pembrolizumab and brentuximab vedotin, followed by pembrolizumab monotherapy. Pembrolizumab has helped patients live longer without their disease worsening, compared to using brentuximab alone. Together, these treatments are expected to lead to a strong overall response. Early studies also suggest that pembrolizumab can improve patients' quality of life. Overall, this combination has potential for effectively managing this type of lymphoma. ^{1 2 5 6 7}

Who Is on the Research Team?

Tarsheen Sethi

Principal Investigator

Yale University

Are You a Good Fit for This Trial?

Adults with a confirmed diagnosis of T-cell Non-Hodgkin lymphoma, including various subtypes like PTCL and CTCL, who have CD30 positive cells and have failed at least one prior therapy. Participants must be over 18, not pregnant or breastfeeding, willing to use contraception, and have good organ function. Exclusions include those with certain other health conditions or treatments that could interfere with the trial.

Inclusion Criteria

I have a lymphoma with a detectable tumor larger than 1.5 cm.

Participant provides written informed consent for the trial

I am fully active or can carry out light work.

Exclusion Criteria

I am currently fighting an infection that needs treatment.

Known psychiatric or substance abuse disorders

History or current evidence of conditions that might interfere with the study

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive up to 16 cycles of brentuximab and pembrolizumab, followed by up to 19 additional cycles of pembrolizumab monotherapy

35 cycles

Response Assessment

Response assessments occur at pre-specified intervals, with primary response assessment after 3 cycles

63 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

What Are the Treatments Tested in This Trial?

Interventions

• Brentuximab vedotin
• Pembrolizumab

Trial Overview The study is testing the combination of Pembrolizumab and Brentuximab Vedotin in patients with relapsed/refractory T-cell lymphoma. It's an open-label phase 2 trial where both drugs are given for up to 16 cycles if effective; Pembrolizumab may continue for a total of 35 cycles. The goal is to see if this combo can achieve around a 65% overall response rate.

How Is the Trial Designed?

Group I: Brentuximab vedotin (brentuximab) and pembrolizumab Experimental Treatment 2 Interventions

All subjects are scheduled to receive up to 16 cycles of combinatorial treatment with brentuximab + pembrolizumab, followed by up to 19 additional cycles of pembrolizumab monotherapy. After receiving 35 total doses of pembrolizumab (i.e. scheduled for 16 doses in the combinatorial setting and 8 doses as monotherapy), a subject's pembrolizumab treatment will be complete.

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?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

Sethi

Lead Sponsor

Trials

2

Recruited

70+

Tarsheen Sethi

Lead Sponsor

Trials

2

Recruited

70+

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 (BV) is an effective targeted therapy for CD30-positive primary cutaneous T-cell lymphoma (CTCL), showing response rates over 75% in clinical trials, including a Phase III trial that demonstrated significant improvements compared to standard treatments.

While BV is associated with manageable adverse effects, including frequent peripheral neuropathy, it does not increase the risk of severe adverse effects, making it a promising option for patients with refractory CTCL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brentuximab vedotin therapy for CD30-positive cutaneous T-cell lymphoma: a targeted approach to management. Scarisbrick, JJ.[2019]

In the international phase III ALCANZA trial, brentuximab vedotin, a CD30-directed antibody-drug conjugate, showed significantly better clinical responses in patients with cutaneous T-cell lymphomas compared to standard treatments like methotrexate or bexarotene.

This study highlights the efficacy of brentuximab vedotin as a more effective treatment option for patients with this type of lymphoma, suggesting a promising advancement in targeted cancer therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brentuximab Beats Standard Therapies for CTCL. [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]

A phase 2 study demonstrated promising efficacy of brentuximab vedotin, an antibody-drug conjugate, in treating patients with relapsed or refractory peripheral T-cell lymphoma (PTCL).

The results suggest that BV could be a valuable treatment option for patients who have not responded to previous therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Time has come for immunotherapy in PTCL. Bachy, E., Coiffier, B.[2021]

Brentuximab vedotin significantly reduced symptom burden in patients with CD30-expressing cutaneous T-cell lymphoma compared to physician's choice treatments, with a mean maximum reduction in symptom scores of -27.96 versus -8.62, exceeding the minimally important difference.

Quality of life measures, including FACT-G and EQ-5D scores, remained comparable between brentuximab vedotin and physician's choice, indicating that the treatment did not adversely affect patients' overall well-being, even in those experiencing peripheral neuropathy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-reported quality of life in patients with relapsed/refractory cutaneous T-cell lymphoma: Results from the randomised phase III ALCANZA study. Dummer, R., Prince, HM., Whittaker, S., et al.[2020]

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]

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 a phase 3 trial involving 131 patients with CD30-positive cutaneous T-cell lymphomas, brentuximab vedotin demonstrated a significantly higher objective response rate lasting at least 4 months (56.3%) compared to conventional therapies (12.5%), indicating its superior efficacy.

While brentuximab vedotin was associated with a higher incidence of peripheral neuropathy (67% of patients), the overall safety profile was comparable to conventional therapies, with similar rates of grade 3-4 adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brentuximab vedotin or physician's choice in CD30-positive cutaneous T-cell lymphoma (ALCANZA): an international, open-label, randomised, phase 3, multicentre trial. Prince, HM., Kim, YH., Horwitz, SM., et al.[2019]

The ECHELON-2 trial demonstrated that the combination of brentuximab vedotin with cyclophosphamide, doxorubicin, and prednisone (A+CHP) significantly improved progression-free survival in patients with CD30-positive peripheral T-cell lymphomas, with a median of 48.2 months compared to 20.8 months for the standard CHOP regimen.

The safety profile of A+CHP was manageable, with similar rates of adverse events like febrile neutropenia and peripheral neuropathy compared to CHOP, indicating that A+CHP is a viable and effective front-line treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brentuximab vedotin with chemotherapy for CD30-positive peripheral T-cell lymphoma (ECHELON-2): a global, double-blind, randomised, phase 3 trial. Horwitz, S., O'Connor, OA., Pro, B., 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. clinicaltrials.gov clinicaltrials.gov/study/NCT02684292

NCT02684292 | Study of Pembrolizumab (MK-3475) vs. ... The primary hypotheses of this study are that treatment with pembrolizumab prolongs Progression-free Survival (PFS) and Overall Survival (OS) in participants ...

3. yalemedicine.org yalemedicine.org/clinical-trials/phase-2-study-of-pembrolizumab-and-brentuximab-vedotin-in-patients-with-relapsed-refractory-cd30

Phase 2 Study of Pembrolizumab and Brentuximab ... This is a single arm, open label, multicenter study phase 2 study of pembrolizumab and brentuximab in subjects with relapsed/refractory CD30 positive T-cell ...

4. aacrjournals.org aacrjournals.org/clincancerres/article/31/5/848/751942/Phase-II-Open-Label-Trial-of-Brentuximab-Vedotin

Phase II Open-Label Trial of Brentuximab Vedotin with ... This study evaluated responses to BV + pembrolizumab after PD-1 therapy and explored corresponding biomarkers.

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. clinicaltrials.gov clinicaltrials.gov/study/NCT04795869?cond=(T-CELL%20LYMPHOMA,%20SUBCUTANEOUS%20PANNICULITIS-LIKE)%20OR%20(HAVCR2)&rank=5

Brentuximab Vedotin and Pembrolizumab in Treating ... This phase II clinical trial studies how well giving brentuximab vedotin together with pembrolizumab in treating patients with peripheral T-cell lymphoma ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11873802/

Phase II Open-Label Trial of Brentuximab Vedotin with ... This study tested the potential of using brentuximab vedotin, an anti-CD30 antibody–drug conjugate (ADC), in combination with pembrolizumab to resensitize ...