Brentuximab Vedotin + Pembrolizumab for Advanced Cancers

Not currently recruiting at 115 trial locations

Overseen By Seagen Trial Information Support

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Seagen, a wholly owned subsidiary of Pfizer

Must be taking: PD-1 inhibitors

Must not be taking: Immunosuppressive chemotherapy

Disqualifiers: CNS metastases, Carcinomatous meningitis, 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: Up to approximately 2 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the combination of two treatments, brentuximab vedotin (an antibody-drug conjugate) and pembrolizumab (an immunotherapy drug), to determine their effectiveness in treating certain advanced cancers that have spread. Researchers aim to assess whether this combination can effectively treat cancers such as specific types of lung cancer, melanoma, or head and neck cancer, particularly after other treatments have failed. The trial will also examine any side effects caused by the treatment. Individuals with these types of metastatic cancers who have experienced treatment progression or have not yet received certain treatments might be suitable candidates for this trial. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people, offering participants a chance to contribute to significant advancements in cancer treatment.

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

The trial protocol does not specify if you need to stop your current medications. However, if you are in Cohorts 1-4 and have melanoma, you must be on PD-1 checkpoint inhibitor therapy or have had it as your last treatment within 90 days before joining. Please consult with the trial coordinators for more details.

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 in Cohorts 1-4 and have melanoma, you must be on or have recently been on PD-1 checkpoint inhibitor therapy.

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

Research has shown that using brentuximab vedotin and pembrolizumab together is generally safe. Past studies found no new safety issues with this combination, and importantly, no deaths were linked to treatment side effects. This indicates that most patients can tolerate the combination well. Both brentuximab vedotin and pembrolizumab are already used to treat other conditions, which helps reassure about their safety. However, it is important to remember that all treatments can have side effects, and this trial aims to learn more about them. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Brentuximab Vedotin and Pembrolizumab for advanced cancers because it offers a novel approach to treatment. Unlike traditional chemotherapy, which targets all rapidly dividing cells, Brentuximab Vedotin is an antibody-drug conjugate that specifically targets cancer cells expressing the CD30 protein, delivering a potent drug directly to the tumor and sparing healthy cells. Pembrolizumab, on the other hand, is an immune checkpoint inhibitor that helps the immune system recognize and attack cancer cells more effectively. This dual mechanism not only aims to enhance treatment efficacy but also has the potential to reduce side effects compared to conventional therapies. This innovative approach could lead to improved outcomes for patients with advanced cancers who have limited options.

What evidence suggests that brentuximab vedotin and pembrolizumab could be effective for advanced cancers?

Research has shown that combining brentuximab vedotin and pembrolizumab may help treat various types of advanced cancer, where the disease has spread to other parts of the body. Studies with patients who have advanced non-small cell lung cancer and advanced skin cancer (melanoma) demonstrated positive results when patients received at least one dose of both treatments. In this trial, participants will receive the combination therapy of brentuximab vedotin and pembrolizumab. Pembrolizumab alone has been shown to prolong the time before cancer worsens. Another study found that pembrolizumab improved the quality of life more than brentuximab vedotin in some cancer types. These findings suggest that using these two treatments together may effectively treat certain advanced cancers. ^{1 2 3 4 5}

Who Is on the Research Team?

Pfizer CT.gov Call Center

Principal Investigator

Pfizer

Are You a Good Fit for This Trial?

This trial is for adults with certain metastatic cancers (oral, melanoma, lung) that have not responded to previous treatments. They must have tried a PD-1 inhibitor and can't have any active brain metastases or recent other cancer treatments. Good physical health as measured by ECOG score of 1 or less is required.

Inclusion Criteria

My cancer progressed despite treatment with an anti-PD-1 therapy.

My skin cancer has worsened despite treatment with a PD-1 inhibitor.

I am currently on PD-1 therapy or had my last dose within the last 90 days.

Exclusion Criteria

I have cancer that has spread to my brain or spinal cord.

I haven't had immunosuppressive treatments or any immunotherapy except PD-1 inhibitors in the last 4 weeks.

I have not had another cancer or any signs of cancer in the last 3 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive brentuximab vedotin and pembrolizumab to treat metastatic solid tumors

Up to approximately 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to approximately 3 years

What Are the Treatments Tested in This Trial?

Interventions

• Brentuximab Vedotin
• Pembrolizumab

Trial Overview The study tests the combination of brentuximab vedotin and pembrolizumab in treating advanced cancers that spread to other body parts. It aims to see how well these drugs work together across different cancer types in multiple groups of patients.

How Is the Trial Designed?

Group I: Combination Therapy Experimental Treatment 2 Interventions

brentuximab vedotin + pembrolizumab

Brentuximab Vedotin is already approved in United States, European Union for the following indications:

Approved in United States as Adcetris for:

• Hodgkin lymphoma
• Systemic anaplastic large cell lymphoma
• Primary cutaneous anaplastic large cell lymphoma
• CD30-expressing mycosis fungoides
• Peripheral T-cell lymphoma

Approved in European Union as Adcetris for:

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

Who Is Running the Clinical Trial?

Seagen, a wholly owned subsidiary of Pfizer

Lead Sponsor

Trials

20

Recruited

4,900+

Seagen Inc.

Lead 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

Pembrolizumab, an immunotherapy for advanced non-small-cell lung cancer (NSCLC), significantly improves progression-free and overall survival compared to traditional chemotherapy, with fewer side effects, particularly in patients with high PD-L1 expression (≥50%).

In combination with pemetrexed and carboplatin, pembrolizumab also enhances treatment effectiveness and maintains manageable toxicity, leading to a shift in first-line treatment strategies for advanced NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab as first-line therapy for metastatic non-small-cell lung cancer. Reck, M.[2018]

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]

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]

Nivolumab and pembrolizumab are FDA-approved monoclonal antibodies that target PD-1, helping to enhance T cell activity against cancer by blocking the PD-1/PD-L1 interaction, which allows cancer cells to escape immune detection.

Both drugs have shown efficacy across multiple cancer types, including melanoma and non-small cell lung cancer, and are considered interchangeable options for treating these conditions, which may help manage the rising costs of cancer therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab and pembrolizumab: Monoclonal antibodies against programmed cell death-1 (PD-1) that are interchangeable. Prasad, V., Kaestner, V.[2022]

In a phase Ib trial (KEYNOTE-028) involving 43 patients with advanced anal carcinoma, pembrolizumab showed a manageable safety profile, with 64% experiencing treatment-related adverse events, but no treatment-related deaths or discontinuations.

Among patients with PD-L1-positive tumors, pembrolizumab achieved a 17% overall response rate and a 58% disease control rate, indicating promising antitumor activity and supporting further research in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and antitumor activity of the anti-PD-1 antibody pembrolizumab in patients with recurrent carcinoma of the anal canal. Ott, PA., Piha-Paul, SA., Munster, P., et al.[2021]

The maximum tolerated doses (MTDs) for the combination of pembrolizumab and trametinib were established, with concurrent dosing showing a lower objective response rate (0%) compared to intermittent dosing (27%).

While the combination treatment had manageable safety profiles, with 31% of patients experiencing grade 3/4 treatment-related adverse events in the concurrent group, the overall antitumor activity was limited, suggesting that this combination may not be highly effective for solid tumors and BRAF wild-type melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

KEYNOTE-022: Pembrolizumab with trametinib in patients with BRAF wild-type melanoma or advanced solid tumours irrespective of BRAF mutation. Maio, M., Carlino, MS., Joshua, AM., et al.[2022]

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

In a long-term study of 123 patients with advanced nonsquamous NSCLC, the combination of pembrolizumab with pemetrexed-carboplatin significantly improved the objective response rate (58% vs. 33%) and progression-free survival (24.5 months vs. 9.9 months) compared to chemotherapy alone.

Patients who completed 2 years of pembrolizumab treatment had a remarkable 92% survival rate at the data cutoff, indicating a durable clinical benefit, while the safety profile remained manageable with no new safety concerns identified.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Overall Survival From KEYNOTE-021 Cohort G: Pemetrexed and Carboplatin With or Without Pembrolizumab as First-Line Therapy for Advanced Nonsquamous NSCLC. Awad, MM., Gadgeel, SM., Borghaei, H., et al.[2021]

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]

In the JAVELIN Lung 100 trial involving 1214 patients with advanced NSCLC, avelumab showed longer median progression-free survival (PFS) compared to platinum-based chemotherapy (8.4 months vs. 5.6 months), indicating its potential efficacy as a first-line treatment.

Although avelumab demonstrated longer median overall survival (OS) compared to chemotherapy (20.1 months vs. 14.9 months), the differences were not statistically significant, suggesting that while avelumab may be beneficial, it did not meet the primary objective of the trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Avelumab Versus Platinum-Based Doublet Chemotherapy as First-Line Treatment for Patients With High-Expression Programmed Death-Ligand 1-Positive Metastatic NSCLC: Primary Analysis From the Phase 3 JAVELIN Lung 100 Trial. Reck, M., Barlesi, F., Yang, JC., et al.[2023]

Pembrolizumab (Keytruda) is an approved treatment for metastatic or locally advanced esophageal and gastroesophageal junction cancer, indicating its efficacy in targeting these specific cancer types.

It is used in combination with platinum- and fluoropyrimidine-based chemotherapy, suggesting a synergistic approach to enhance treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab Approved for Esophageal or Gastroesophageal Cancer. Aschenbrenner, DS.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04609566

Study Details | NCT04609566 | Brentuximab Vedotin With ... This trial will find out whether brentuximab vedotin and pembrolizumab work together to treat different types of cancer.

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

Phase II Open-Label Trial of Brentuximab Vedotin with ... A total of 55 patients with metastatic non–small cell lung cancer and 58 patients with metastatic cutaneous melanoma received ≥1 dose of BV + pembrolizumab.

4. 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.

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.2617

Phase 2 trial of brentuximab vedotin (BV) with ... This ongoing, multi-cohort, multicenter, open-label trial evaluating the efficacy and safety of BV+pembro in patients (pts) with anti-PD-1 refractory solid ...