Pembrolizumab + Ibrutinib for Melanoma

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Mayo Clinic

Must not be taking: Warfarin, Strong CYP3A inhibitors

Disqualifiers: Pregnancy, Uveal melanoma, Autoimmune disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 7

Duration: 28 days for cycle 1, 21 days for subsequent cycles

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the optimal dose of ibrutinib (Imbruvica), a cancer treatment, when combined with pembrolizumab (KEYTRUDA), an immunotherapy drug, for treating stage III-IV melanoma that cannot be surgically removed. The researchers seek to assess whether this combination can enhance the immune system's ability to attack the cancer and halt tumor growth. Patients with stage III-IV melanoma, particularly those whose condition has worsened after previous treatments, might be suitable candidates. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering patients the opportunity to be among the first to receive this new combination therapy.

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

The trial does not specify if you need to stop taking your current medications, but you cannot use warfarin, other vitamin K antagonists, or strong CYP3A inhibitors. If you're on these, you may need to stop or switch medications before joining.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research is exploring the combined use of ibrutinib and pembrolizumab to treat advanced melanoma. In earlier studies, patients took both drugs to assess their effectiveness and safety. The main goal was to determine the optimal dose that patients can tolerate without serious side effects.

Studies have shown that while the combination can cause some side effects, they are usually manageable. Common side effects include tiredness, skin rash, and diarrhea, similar to those seen when each drug is used alone.

Since this trial remains in the early stages, researchers are carefully monitoring the treatment for safety. They are closely observing for any serious or unexpected issues to ensure the benefits outweigh the risks. Prospective participants should discuss with the doctors involved to understand what participation might entail. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about combining pembrolizumab and ibrutinib for melanoma because this duo targets the cancer in a unique way. Pembrolizumab, an immune checkpoint inhibitor, unleashes the body’s immune system to recognize and attack melanoma cells. Meanwhile, ibrutinib, originally used to treat certain blood cancers, may inhibit pathways that help melanoma cells survive. This combination could offer a novel approach compared to the current standard treatments like targeted therapies and other immune checkpoint inhibitors, potentially enhancing effectiveness and broadening treatment options for patients with melanoma.

What evidence suggests that pembrolizumab and ibrutinib might be an effective treatment for melanoma?

Research shows that using ibrutinib with pembrolizumab, as studied in this trial, might strengthen the body's defense against melanoma, a type of skin cancer. Pembrolizumab, an immunotherapy, helps the immune system attack cancer cells, potentially improving survival rates for people with advanced melanoma. Evidence from real-world use confirms that pembrolizumab alone effectively treats advanced melanoma. In contrast, ibrutinib blocks certain enzymes that cancer cells need to grow, which may help prevent tumors from spreading. Early studies suggest that combining these two drugs, as done in this trial, could further enhance the immune system's ability to fight melanoma. ^{1 3 6 7 8}

Who Is on the Research Team?

Matthew S. Block, MD, PhD

Principal Investigator

Mayo Clinic in Rochester

Are You a Good Fit for This Trial?

This trial is for adults with advanced melanoma (stage III-IV) that can't be surgically removed. They should have a certain level of physical fitness, adequate organ function, and no recent treatments or severe illnesses that could interfere with the study. Pregnant women and those not using contraception are excluded.

Inclusion Criteria

My melanoma cannot be surgically removed and has spread beyond its original site.

My liver function tests are within the required range.

I can take care of myself and am up and about more than half of my waking hours.

Exclusion Criteria

I have not had any major surgery in the last 28 days.

I have been treated with ibrutinib or other BTK inhibitors before.

I am currently breastfeeding.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive ibrutinib orally daily and pembrolizumab intravenously as part of a dose-escalation study

28 days for cycle 1, 21 days for subsequent cycles

Cycle 1: 1 visit (in-person), Subsequent cycles: 1 visit every 21 days (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Every 6 months for 5 years

Follow-up visits every 6 months

What Are the Treatments Tested in This Trial?

Interventions

• Ibrutinib
• Pembrolizumab

Trial Overview The trial is testing the combination of two drugs: Pembrolizumab, an antibody that may boost the immune system's attack on cancer, and Ibrutinib, which might stop tumor growth by blocking specific enzymes. The goal is to find the best dose of Ibrutinib to use alongside Pembrolizumab.

How Is the Trial Designed?

Group I: Treatment (ibrutinib, pembrolizumab) Experimental Treatment 3 Interventions

Patients receive ibrutinib PO daily on days 1-28 of cycle 1 and days 1-21 of cycle 2 and subsequent cycles. Patients also receive pembrolizumab IV over 30 minutes on day 8 of cycle 1 and day 1 of cycle 2 and subsequent cycles. Cycle 1 continues for 28 days and subsequent cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

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

Approved in European Union as Imbruvica for:

• Chronic lymphocytic leukemia
• Mantle cell lymphoma
• Waldenström's macroglobulinemia
• Marginal zone lymphoma
• Graft-versus-host disease

Approved in United States as Imbruvica for:

• Chronic lymphocytic leukemia/small lymphocytic lymphoma
• Mantle cell lymphoma
• Waldenström's macroglobulinemia
• Marginal zone lymphoma
• Graft-versus-host disease

Approved in Canada as Imbruvica for:

• Chronic lymphocytic leukemia
• Mantle cell lymphoma
• Waldenström's macroglobulinemia
• Marginal zone lymphoma

Approved in Japan as Imbruvica for:

• Chronic lymphocytic leukemia
• Mantle cell lymphoma
• Waldenström's macroglobulinemia

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39967670/

Phase I study of pembrolizumab in combination with ... Therefore, combining ibrutinib and pembrolizumab could potentially induce an increase in Th1 immune polarity in melanoma patients. We ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12454464/

Real-World Outcomes of Pembrolizumab in Advanced ... Real-world Australian data indicate pembrolizumab monotherapy for advanced melanoma achieves survival outcomes consistent with clinical trials, ...

3. figshare.com figshare.com/articles/dataset/Data_Sheet_1_Phase_I_study_of_pembrolizumab_in_combination_with_ibrutinib_for_the_treatment_of_unresectable_or_metastatic_melanoma_docx/28341809

Data Sheet 1_Phase I study of pembrolizumab in ... Therefore, combining ibrutinib and pembrolizumab could potentially induce an increase in Th1 immune polarity in melanoma patients. We ...

4. clinical-lymphoma-myeloma-leukemia.com clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(20)30797-7/pdf

CLL-229: Efficacy of Immune Checkpoint Inhibitors in ... After 6 months of ibrutinib treatment we observed a decrease of circulating CLL cells, which was paralleled by a reduction of CD3+,.

5. mayo.edu mayo.edu/research/clinical-trials/diseases-conditions/metastatic-melanoma

Metastatic Melanoma Clinical Trials This phase II trial studies how well pembrolizumab and ibrutinib work in treating patients with stage III-IV melanoma that cannot be removed by surgery.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03021460

Pembrolizumab and Ibrutinib in Treating Patients With ... To assess the safety and adverse-event profiles of combination of ibrutinib with pembrolizumab in patients with advanced melanoma. II. To evaluate the overall ...

7. researchgate.net researchgate.net/publication/388680973_Phase_I_study_of_pembrolizumab_in_combination_with_ibrutinib_for_the_treatment_of_unresectable_or_metastatic_melanoma

Phase I study of pembrolizumab in combination with ibrutinib for ... Therefore, combining ibrutinib and pembrolizumab could potentially induce an increase in Th1 immune polarity in melanoma patients. We hypothesize that the ...

8. frontiersin.org frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1491448/epub

Phase I study of pembrolizumab in combination with ibrutinib for ... Although activated CD8+ T cells are thought to be associated with favorable outcomes, several other possible explanations of the data exist. First, the ...