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Metastatic MelanomaPhase 1NCT03021460

Pembrolizumab and Ibrutinib in Treating Patients With Stage III-IV Melanoma That Cannot Be Removed by Surgery

A Phase 1 study testing Ibrutinib, Laboratory Biomarker Analysis and Pembrolizumab in people with Metastatic Melanoma and Stage III Cutaneous Melanoma AJCC v7, run by Mayo Clinic at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This phase I trial studies the best dose of ibrutinib when given together with pembrolizumab in treating patients with stage III-IV melanoma that cannot be removed by surgery. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Ibrutinib, Laboratory Biomarker Analysis and Pembrolizumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
20 participants
Where
1 siteUnited States
Study dates
31 Jan 2017to 31 Dec 2025
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • PRE-REGISTRATION- INCLUSION CRITERIA
  • Diagnosis of unresectable stage III or metastatic melanoma (stage IV) not amenable to local therapy
  • At least one non-nodal lesion considered measurable by Response Evaluation Criteria in Solid Tumors (RECIST) criteria (that is, a lesion whose longest diameter can be accurately measured as >= 1.0 cm with computed tomography [CT] scan, CT component of a positron emission tomography [PET]/CT, or magnetic resonance imaging [MRI]) or at least one malignant lymph node is considered measurable by RECIST criteria (that is, its short axis is >= 1.5 cm when assessed by CT scan)
  • NOTE: tumor lesions in a previously irradiated area are not considered measurable disease
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2
  • Provide informed written consent
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  • Patient is willing to undergo treatment and monitoring at the enrolling institution
  • Willing to provide tissue and blood samples for correlative research purposes
  • REGISTRATION- INCLUSION CRITERIA
  • Histologic or cytologic confirmation of unresectable stage III or metastatic melanoma (stage IV) not amenable to local therapy
  • Only if patient has had previous exposure to anti-PD-1 or anti-PD-L1 therapy:
  • Patient had disease progression on or within 6 months after anti-PD-1/anti-PD-L1 therapy in the metastatic setting OR
  • Patient had disease progression within 6 months after the last dose of adjuvant/neoadjuvant anti-PD-1/anti-PD-L1 treatment
  • Absolute neutrophil count (ANC) >= 1000/mm^3 (obtained =< 14 days prior to registration)
  • Platelet count >= 75,000/mm^3 (obtained =< 14 days prior to registration)
  • Criteria must be met without a transfusion =< four weeks prior to registration
  • Hemoglobin >= 9.0 g/dL (obtained =< 14 days prior to registration)
  • Total bilirubin =< 1.5 X upper limit of normal (ULN); if total bilirubin > 1.5 X ULN then direct bilirubin =< ULN (obtained =< 14 days prior to registration)
  • Aspartate aminotransferase (aspartate transaminase [AST]) and alanine aminotransferase (alanine transaminase [ALT]) =< 2.5 x ULN OR =< 5 X ULN for patients with liver metastases (obtained =< 14 days prior to registration)
  • Creatinine =< 1.5 X ULN and creatinine clearance (CrCL) >= 30 ml/min per Cockcroft Gault formula (obtained =< 14 days prior to registration)
  • Patients of childbearing potential only, negative urine pregnancy test done =< 7 days prior to study registration

Who cannot join

  • PRE-REGISTRATION EXCLUSION CRITERIA
  • Any of the following:
  • Pregnant women
  • Nursing women
  • Men or women of childbearing potential who are unwilling to employ adequate contraception within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study medication; adequate contraception is defined as 2 methods of birth control (e.g., hormonal contraceptives, intrauterine device, diaphragm with spermicide, cervical cap with spermicide, male condoms, or female condom with spermicide) or prior surgical sterilization, or abstinence from heterosexual activity
  • Prior treatment with ibrutinib or prior exposure to BTK inhibitors
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  • Uveal melanoma
  • Current use of warfarin or other vitamin K antagonists
  • Require continuous treatment with a strong CYP3A inhibitor
  • Currently participating or has participated in a study of an investigational cancer therapy agent or using an investigational device within 28 days prior to study registration
  • Live vaccines within 28 days prior to study pre-registration
  • Invasive surgical procedure within 28 days prior to study pre-registration
  • History of clinically severe (e.g., requires chronic immunosuppressive therapy, [e.g., cyclosporine A, tacrolimus]) autoimmune disease (e.g., ulcerative colitis, lupus), or history of organ transplant
  • Known history of human immunodeficiency virus (HIV) infection, active infection with hepatitis B virus or hepatitis C virus, or any uncontrolled active systemic infection
  • Gastrointestinal disease that might inhibit ibrutinib absorption (e.g., malabsorption syndrome, resection of the stomach or a large portion of small bowel, or partial/complete bowel obstruction), or unable to swallow capsules
  • Active central nervous system metastases and/or carcinomatous meningitis
  • Note: Patients with untreated brain metastasis will be excluded; patients with previously treated brain metastases may participate provided they meet the following criteria:
  • Inactive (without evidence of progression which is documented by CT or MRI within 90 days prior to registration), AND
  • On =< 10 mg/day prednisone or equivalent for at least 28 days prior pre-registration
  • Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
  • Clinically significant cardiovascular disease such as unstable angina, myocardial infarction, or acute coronary syndrome within =< 180 days prior to registration, symptomatic or uncontrolled arrhythmia, congestive heart failure, or any class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification
  • Other active malignancy =< 3 years prior to pre-registration; note: if there is a history of prior malignancy, the patient must not be receiving other specific treatment for cancer
  • EXCEPTIONS: Non-melanotic skin cancer or carcinoma-in-situ of the cervix
  • Currently active, clinically significant cardiovascular disease, such as uncontrolled arrhythmia or class 3 or 4 congestive heart failure as defined by the New York Heart Association Functional Classification; or a history of myocardial infarction, unstable angina, or acute coronary syndrome =< 6 months prior to pre-randomization
  • Known bleeding disorders (von Willebrand's disease or hemophilia)
  • History of ischemic stroke or intracranial hemorrhage =< 180 days prior to pre-registration
  • Currently active, clinically significant hepatic impairment Child-Pugh class A, B or C according to the Child Pugh classification
  • Unresolved toxicities from prior anti-cancer therapy, defined as not resolved to Common Terminology Criteria for Adverse Events (CTCAE, version [v]4.0) grade 0 or 1, or to the levels dictated in the inclusion/exclusion criteria with the exceptions of alopecia and peripheral neuropathy
  • REGISTRATION- EXCLUSION
  • Failure to confirm histologically or cytologically unresectable stage III or metastatic melanoma (stage IV) not amenable to local therapy
  • Prior chemotherapy, immunotherapy, radioactive, or biological cancer therapy (including monoclonal antibody [mAb]) =< 28 days prior to registration
  • Received a strong cytochrome P450 (CYP) 3A inhibitor =< 7 days prior to registration
  • Concurrent systemic immunosuppressant therapy =< 21 days prior to registration
  • Recent infection requiring systemic antibiotic treatment that was completed =< 14 prior to registration

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Mayo Clinic in Rochester

    Rochester, Minnesota, 55905

Other trials in United States

About this study

Official title: Phase I Study of Pembrolizumab in Combination With Ibrutinib in the Treatment of Unresectable or Metastatic Melanoma

This phase I trial studies the best dose of ibrutinib when given together with pembrolizumab in treating patients with stage III-IV melanoma that cannot be removed by surgery. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Ibrutinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving pembrolizumab and ibrutinib may work better in treating patients with melanoma.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the maximum tolerated dose of ibrutinib in combination with pembrolizumab in patients with advanced melanoma. (Phase I) II. To estimate the overall response rate treated at the maximum tolerated dose of ibrutinib in combination with pembrolizumab in patients with advanced melanoma. (Dose expansion cohort)

SECONDARY OBJECTIVES:

  1. To assess the safety and adverse-event profiles of combination of ibrutinib with pembrolizumab in patients with advanced melanoma.

II. To evaluate the overall response rate (ORR) in patients advanced melanoma receiving ibrutinib and pembrolizumab.

III. To evaluate the duration of response, progression-free survival (PFS), and overall survival (OS) in patients with advanced melanoma receiving ibrutinib and pembrolizumab.

IV. To assess the effect of treatment with ibrutinib and pembrolizumab on Th1/Th2 immune polarity.

EXPLORATORY OBJECTIVES:

  1. To assess the CD8 T cell response to multiple melanoma-associated antigens, and to correlate CD8 T cell responses with changes in Th1/Th2 immune polarity.

II. To assess changes in plasma cytokines induced by treatment with ibrutinib and pembrolizumab.

III. To assess the change in potential biomarkers, such as tumor-bound and soluble PD-L1 levels and tumor-infiltrating lymphocytes, that may correlate with treatment responses.

OUTLINE: This is a dose-escalation study of ibrutinib.

Patients receive ibrutinib orally (PO) daily on days 1-28 of cycle 1 and days 1-21 of cycle 2 and subsequent cycles. Patients also receive pembrolizumab intravenously (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.

After completion of study treatment, patients are followed up every 6 months for 5 years.

Being tested
Ibrutinib, Laboratory Biomarker Analysis, Pembrolizumab
Medical subject headings
Melanoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • IbrutinibDrug

    Also called BTK Inhibitor PCI-32765, CRA-032765, Imbruvica, PCI-32765

    Given PO

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • PembrolizumabBiological

    Also called Keytruda, Lambrolizumab, MK-3475, SCH 900475

    Given IV

Study groups in NCT03021460
Study groupRoleWhat they receive
Treatment (ibrutinib, pembrolizumab)ExperimentalPatients 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.
Receives: Drug: Ibrutinib; Other: Laboratory Biomarker Analysis; Biological: Pembrolizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximum tolerated dose (Phase I)

    Will be defined as the highest dose level among those tested where at most one out of 6 patients develops a dose limiting toxicity prior to the start of their second course of treatment. The maximum grade of each type of toxicity will be recorded for each patient. For each toxicity reported by dose level, the percentage of patients developing any degree of that toxicity as well as the percentage of patients developing a severe degree (grade 3 or higher) will be determined.

    Measured: Up to start of second course of treatment

  2. Tumor response (dose expansion cohort)

    Estimates of tumor response and binomial confidence intervals will be reported.

    Measured: Up to 5 years

Secondary outcomes (3)

  1. Tumor response evaluated according to Response Evaluation Criteria in Solid criteria (RECIST)

    A patient whose tumor has met the RECIST criteria for complete response or partial response on two consecutive evaluations at least 8 weeks apart is considered to have had a tumor response.

    Measured: Up to 5 years

  2. Progression-free survival

    Will be examined in an exploratory and hypothesis-generating fashion.

    Measured: From study entry to the documentation of disease progression, assessed up to 5 years

  3. Overall survival

    Will be examined in an exploratory and hypothesis-generating fashion.

    Measured: From study entry to death due to any cause, assessed up to 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Jan 2017 (estimated)
  2. Study start31 Jan 2017
  3. Primary completion31 Dec 2025
  4. Study completion31 Dec 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
20 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03021460
Sponsor's protocol ID
MC1577
Other IDs
16-002462
Status last verified
Aug 2026
First submitted
12 Jan 2017
Last updated
1 Sep 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Yao Y, Yan Y, Suman VJ, Dietz AB, Erskine CL, Dimou A, Markovic SN, McWilliams RR, Montane HN, Block MS. Phase I study of pembrolizumab in combination with ibrutinib for the treatment of unresectable or metastatic melanoma. Front Immunol. 2025 Feb 4;16:1491448. doi: 10.3389/fimmu.2025.1491448. eCollection 2025.

    PubMed 39967670

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Ibrutinib, Laboratory Biomarker Analysis and Pembrolizumab in people with Metastatic Melanoma and Stage III Cutaneous Melanoma AJCC v7, run by Mayo Clinic at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 21 inclusion and 34 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 1 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum tolerated dose (Phase I) (time frame: Up to start of second course of treatment). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03021460, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Sep 2026.

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